The biosynthesis of fatty acids most actively occurs in the cytosol of the cells of the liver, intestines, adipose tissue at rest or after eating.
Conventionally, 4 stages of biosynthesis can be distinguished:
1. Formation of acetyl-SCoA from glucose, other monosaccharides or ketogenic amino acids.
2. Transfer of acetyl-SCoA from mitochondria to the cytosol:
may be in complex with carnitine, similar to how higher fatty acids are transported into the mitochondria, but here the transport goes in a different direction, usually in the composition citric acid, formed in the first TCA reaction. Citrate coming from mitochondria in the cytosol is cleaved by ATP-citrate lyase to oxaloacetate and acetyl-SCoA. Oxaloacetate is further reduced to malate, and the latter either passes into mitochondria (malate-aspartate shuttle) or is decarboxylated into pyruvate Malik-enzyme ("apple" enzyme).
3. Formation of malonyl-SCoA from acetyl-SCoA. The carboxylation of acetyl-SCoA is catalyzed by acetyl-SCoA carboxylase, a multienzyme complex of three enzymes.
4. Synthesis of palmitic acid.
It is carried out by the multienzyme complex "fatty acid synthase" (synonym palmitate synthase), which includes 6 enzymes and an acyl-carrying protein (ACP).
The acyl-carrying protein includes a derivative of pantothenic acid, 6-phosphopantetheine (PP), which has an HS group, similar to HS-CoA. One of the complex's enzymes, 3-ketoacyl synthase, also has an HS group in cysteine. The interaction of these groups determines the beginning and continuation of the biosynthesis of fatty acids, namely palmitic acid. Synthesis reactions require NADPH.
In the first two reactions, malonyl-SCoA is sequentially added to the phosphopantetheine of the acyl-carrying protein and acetyl-SCoA to the cysteine of 3-ketoacyl synthase. ketoacyl reductase), dehydration (dehydratase) and again reduction (enoyl reductase) turns into methylene with the formation of a saturated acyl associated with phosphopantetheine.
The acyltransferase transfers the resulting acyl to the cysteine of 3-ketoacyl synthase, malonyl-SCoA is attached to phosphopantetheine, and the cycle is repeated 7 times until a palmitic acid residue is formed. After that, palmitic acid is cleaved off by the sixth enzyme of the complex, thioesterase.
Synthesized palmitic acid, if necessary, enters the endoplasmic reticulum or mitochondria. Here, with the participation of malonyl-S-CoA and NADPH, the chain is extended to C18 or C20. Unsaturated fatty acids (oleic, linoleic, linolenic) can also be extended to form eicosanoic acid derivatives (C20). But the double bond is introduced by animal cells no further than 9 carbon atoms, therefore ω3- and ω6-polyunsaturated fatty acids are synthesized only from the corresponding precursors.
For example, arachidonic acid can be formed in a cell only in the presence of linolenic or linoleic acids. In this case, linoleic acid (18:2) is dehydrogenated to γ-linolenic acid (18:3) and elongated to eicosotrienoic acid (20:3), the latter is further dehydrogenated to arachidonic acid (20:4). This is how fatty acids of the ω6 series are formed.
68. Cholesterol. His chemical structure, biosynthesis and biological role. Causes
Cholesterol belongs to the group of compounds based on the cyclopentane-perhydrophenanthrene ring and is an unsaturated alcohol.
The synthesis of cholesterol in the body is approximately 0.5-0.8 g / day, while half is formed in the liver, about 15% in the intestine, the rest in any cells that have not lost the nucleus. Thus, all body cells are capable of synthesizing cholesterol.
Of the foods richest in cholesterol (in terms of 100 g of product) sour cream (0.002 g), butter(0.03 g), eggs (0.18 g), beef liver (0.44 g). In general, about 0.4 g per day with a normal diet.
Cholesterol is excreted from the body mainly through the intestines: with faeces in the form of cholesterol, which enters with bile, and neutral sterols formed by the microflora (up to 0.5 g / day); in the form of bile acids (up to 0.5 g / day); about 0.1 g is removed as part of the exfoliating epithelium of the skin and sebum,
approximately 0.1 g is converted into steroid hormones (sex, glucocorticoids, mineralocorticoids) and, after their degradation, is excreted in the urine.
Functions of cholesterol
1. Structural - is part of the membranes, causing their viscosity and rigidity.
2. Binding and transport of polyunsaturated fatty acids between organs and tissues as part of low and high density lipoproteins. Approximately 1/4 of all cholesterol in the body is esterified with oleic acid and polyunsaturated fatty acids. In plasma, the ratio of cholesterol esters to free cholesterol is 2:1.
3. It is a precursor of bile acids, steroid hormones (cortisol, aldosterone, sex hormones) and vitamin D.
Biosynthesis of cholesterol occurs in the endoplasmic reticulum. The source of all carbon atoms in the molecule is acetyl-SCoA, which comes here from mitochondria as part of citrate, just as in the synthesis of fatty acids. During the biosynthesis of cholesterol, 18 ATP molecules and 13 NADPH molecules are consumed. The formation of cholesterol occurs in more than 30 reactions, which can be grouped into several stages.
1. Synthesis of mevalonic acid.
2. Synthesis of isopentenyl diphosphate. At this stage, three phosphate residues are attached to mevalonic acid, then it is decarboxylated and dehydrogenated.
3. After combining three molecules of isopentenyl diphosphate, farnesyl diphosphate is synthesized.
4. The synthesis of squalene occurs by the binding of two residues of farnesyl diphosphate.
5. After complex reactions, linear squalene is cyclized to lanosterol.
6. Removal of excess methyl groups, restoration and isomerization of the molecule leads to the appearance of cholesterol.
The transport of cholesterol and its esters is carried out by low and high density lipoproteins.
High density lipoproteins - are formed in the liver de novo, in the blood plasma during the breakdown of chylomicrons, a certain amount in the intestinal wall; approximately half of the particle is occupied by proteins, another quarter by phospholipids, the rest by cholesterol and TAG (50% protein, 7% TAG, 13% cholesterol esters, 5% free cholesterol, 25% PL); the main apoprotein is apo A1, contain apoE and apoCII.
Function: Transport of free cholesterol from tissues to the liver. HDL phospholipids are a source of polyenoic acids for the synthesis of cellular phospholipids and eicosanoids.
Metabolism
1. HDL synthesized in the liver (nascent or primary) contains mainly phospholipids and apoproteins. The remaining lipid components accumulate in it as it is metabolized in the blood plasma.
2. In HDL, the reaction actively proceeds with the participation of lecithin: cholesterol acyltransferase (LCAT reaction). In this reaction, the polyunsaturated fatty acid residue is transferred from PC to free cholesterol with the formation of lysophosphatidylcholine (lPC) and cholesterol esters.
3. Interacts with LDL and VLDL, which are a source of free cholesterol for the LCAT reaction, give cholesterol esters in exchange for HDL.
4. Interacting with VLDL and HM, they receive TAG and give them apoE and apoCII proteins.
5. Through specific transport proteins, free cholesterol is obtained from cell membranes.
6. Interacts with cell membranes, gives away part of the phospholipid shell, thus delivering polyene fatty acids to cells.
7. The accumulation of free cholesterol, TAG, lysoPC and the loss of the phospholipid membrane converts HDL3 (conditionally it can be called "mature") into HDL2 ("residual"). The latter is taken up by hepatocytes via the apoA-1 receptor.
Low density lipoproteins - are formed in hepatocytes de novo and in the vascular system of the liver under the influence of hepatic TAG lipase from VLDL; cholesterol and its esters predominate in the composition, about half are occupied by proteins and phospholipids (25% proteins, 7% triacylglycerols, 38% cholesterol esters, 8% free cholesterol, 22% phospholipids); the main apoprotein is apoB-100; normal content in the blood is 3.2-4.5 g / l, the most atherogenic.
1. Transport of cholesterol into cells that use it for the reactions of synthesis of sex hormones (sex glands), gluco- and mineralocorticoids (adrenal cortex), cholecalciferol (skin), utilizing cholesterol in the form of bile acids (liver).
2. Transport of polyene fatty acids in the form of cholesterol esters to some cells of loose connective tissue (fibroblasts, platelets, endothelium, smooth muscle cells), to the epithelium of the glomerular membrane of the kidneys, to bone marrow cells, to cells of the cornea of the eyes, to neurocytes, to basophils of the adenohypophysis.
Cells of loose connective tissue actively synthesize eicosanoids. Therefore, they need a constant influx of polyunsaturated fatty acids (PUFAs), which is carried out either by the transfer of phospholipids from the HDL shell into cell membranes or by the absorption of LDL, which carry PUFAs in the form of cholesterol esters. A feature of all these cells is the presence of lysosomal acid hydrolases that break down cholesterol esters. Other cells do not have these enzymes.
1. In the blood, primary LDL interact with HDL, giving away free cholesterol and receiving esterified cholesterol. As a result, cholesterol esters accumulate in them, the hydrophobic core increases, and the apoB-100 protein is “pushed out” to the surface of the particle. Thus, primary LDL becomes mature.
2. All LDL-using cells have a high-affinity LDL-specific receptor, the apoB-100 receptor. When LDL interacts with the receptor, lipoprotein endocytosis occurs and its lysosomal breakdown into its constituent parts - phospholipids, proteins (and further to amino acids), glycerol, fatty acids, cholesterol and its esters.
Cholesterol is converted into hormones or incorporated into membranes; excess membrane cholesterol is removed with HDL; if it is impossible to remove cholesterol, part of it is esterified with oleic acid by the enzyme acyl-SCoA:cholesterol acyltransferase (AChAT); PUFAs brought with cholesterol esters are used for the synthesis of eicosanoids or phospholipids.
About 50% of LDL interact with apoB-100 receptors on hepatocytes and approximately the same amount is absorbed by cells of other tissues.
Synthesis in smooth eps.
Glycerol-3-phosphate + 2 acetyl CoA -> Diacylglycerol, it is hydrophilic enough to be incorporated into the ER membrane, then heads are hung on DAG. This is how the synthesis of PC, PI, PE, FS occurs
1) FS in FE exchange of heads.
2) PE - in three enzymatic reactions in PC
Scramblase enzyme works without ATP. Drags FH and PHI from the outer membrane inward. Different phospholipids on different sides. Asymmetry.
Enzymes insert ceramides into the inner leaflet of the ER membrane. As a result, from a smooth EPS. bubble buds.
This vesicle is embedded in the golgi apparatus.
Some ceramides bind to phosphate ions, and choline or ethanolamine goes to the head = sphingomyelins are formed. Other ceramides cling to carbohydrates and produce gangliosides or cerebrosides.
Then the vesicle buds again and goes to the cytoplasmic membrane where, upon insertion, the vesicle is inverted and the lipids change places.
Asymmetry of the lipid bilayer. The outer and inner layers are different.
During apoptosis in smooth eps, scramblase pumps PS to the outer part of the membrane from the inner one. -> outer membrane of the cell. is a marker for macrophages.
QUESTION NUMBER 1. If scramblase brings PS to the outer part of the ER (cytosolic), then with inversion of the subsequent vesicle in the CM, PS will be on the inside of the membrane, where it cannot be a marker for macrophages.
What did I not understand, or did Baskakov say the wrong thing? Can all the same from external to internal scramblaza shakes?
Asymmetry
1) Glycolipids are always on the outer layer.
2) The outer monolayer contains more saturated fats. Less saturated in the inner
3) The composition of lipids differs in layers.
Asymmetry support.
1) Flip flop (spontaneous)
2) Flipase proteins. ABC conveyors. There is an ATP binding site. Actively transfer phospholipids.
3) FE of the lower monolayer can be converted into PC and transferred to the outer monolayer.
4) PE and PS are transferred from the lower monolayer to the upper one with the help of scramblase of the cytoplasmic membrane.
The fluidity of the membrane depends on the ratio of saturated and unsaturated fatty acids.
Saturated = membrane gelled
Not saturated = (bends of lipids), gel-sol state of the membrane.
Membrane phase transition regulator = cholesterol. Binds fat ponytails. Regulates phase transitions. It liquefies the solid, thickens the liquid.
Membrane proteins
1) Integral proteins
2) Semi-integral (half)
3) Peripheral proteins.
Integral.
Functions:
1. Transport. Protein channels, pumps, carriers.
2. Reception.
3. Adhesion (cell attachment to substrates, cell adhesion)
4. Enzymatic. Adanelate cyclase, phospholipase….
semi-integral proteins.
Functions:
Enzymatic.
peripheral proteins.
Functions:
1. Skeleton.
2. Alarm.
3. Enzymatic.
25-27 a.k. on average penetrate the membrane - alpha helix = trans membrane. segment. Supramembranous, trans-membrane, cytosolic (sub-membrane) domains. (within proteins) 16-18 a.a. Beta fold region.
integral proteins. = trans-membrane
1) Permeate the membranes once. The C and N ends can be on either side. Implement only alpha helix. Functions: adhesion, reception.
2) Permeate the membrane many times. They can realize pure alpha structure, pure beta layers, combinations. Barrels are formed in the same way. Functions: transport, reception.
Proteins outside the bi layer but associated with it.
1) The protein is associated with the membrane; there is a prinyl group. (membrane anchorage) most of the protein in the medium.
2) The protein is linked to FI through 5 sugar residues.
Glycosyl phosphatidylinazitol anchor. (GPI)
ALL are integral proteins due to strong interaction with the membrane. Integrity of a protein = degree of association with the membrane. High = integral proteins.
semi-integral proteins.
One protein. prostaglandin synthase. Participates in metabolism. Arachidonic acid.
Peripheral Squirrels. Bound to the membrane by weak electrostatic interactions (easy to pull out of the membrane)
One new protein, annexin. Which is directly related to one lipid.
Another classification of membrane proteins.
The place of synthesis of membrane proteins in the rough ER,
Squirrels. EPS membrane. They bud in vesicles. -> Golgi apparatus (there is glycosylation, hanging carbohydrates) The bubble approaches the membrane (CM.) and merges. Integration after the golgi occurs instead of both glycolipids and glycoproteins.
amphitropic proteins.
2 locations. They can anchor into the membrane. (they have a hydrophobic conformation) drawing
Solubolization. Isolation of proteins.
Peripheral They are easily separated when the ionic value of the solutions is changed.
Integral and semi-integral should be treated with detergents.
GPI anchor in tryponos. (sleeping sickness)
Variant proteins hide non-variant proteins. Variable 1 gene. after entering the body. The tryponosome cuts off the variant proteins (they are glycoproteins) and synthesizes new virational proteins.
Proteins that only realize the alpha helix
Alfie helices easily change conformation and easily slide relative to each other.
Bacteriorhodopsin. Was isolated in the form of a two-dimensional crystal
Proteins implementing the beta fold structure
Pore-turning proteins (family)
1) PORINS Outer membrane of mitochondria. + outer membrane Gram negative bacteria. 16 beta folds of 13 amino acids. This protein = trimmer.
2) PERFORINA. Produced by NK cells. Antitumor and antiviral resistance.
3) C9 proteins of the coscade component.
transmembrane transport.
Passive and active.
Passive transport
1) Simple diffusion
Oxygen, water, carbon dioxide, carbon monoxide… Not very specific. Velocity = proportional to the gradient of transported molecules on both sides of the membrane.
2) Facilitated diffusion (substrate specificity)
1. Channels.
Passive trance. Along the gradient. Crayons are water-soluble molecules and ions. The channels form a hydrophilic pore.
2. Carriers
Passive transport. Reversible conformational change. Also no tomorrow aft
ACTIVE TRANSPORT.
Carriers. Through the electrochemical gradient. They bind strongly to the substrate. And change their conformation during transfer. 12 transmembrane domains. Or 2 subunits of 6 transmembrane domains (in any case, 12 transmembrane)
UNIPORT = one ion one way
SYMPORT = 2 molecules in one direction
Antiport = parallel input of one ion and output of another
Channels are:
Potential dependent (changes in potential)
Ligand-dependent
1) Ion-dependent. Potassium, sodium, calcium
2) Mediator Aceticholine.
3) Nucleotide. cGMP
The principle of organization of ion channels.:
3 channel organization options
1) 4x subunit (CE) Carry one type of ion. Highly selective. Sodium, calcium, etc. All voltage-dependent.
2) 5 sub. Medium selective. 2-3 types of ions are dragged through. Acetylcholine receptor and at the same time a channel. (repeat for textbook exam)
3) 6 subunits. Gap contacts. Nexuses. 6 connexins form a conexon. Low selectivity.
AQUAPORINS
Under the influence of vasopressin and as a result of the need to transport water. Proteins weighing 30KDa. Aquaporins. (first discovered on erythrocytes and podocytes). On tonoplasts, cytoplasmic membranes. Transport passively. By phosphorylation activity.
Concepts about ABC transporters.
ATF bindins cassettes.
ABC conveyors. 2 classes
1) MDR 1 (multiple drug resistance) Glycoprotein P
2) MDR 2 Flipases
Glycoprotein P (shown in the picture) transports chlorine. In cancer cells, the membrane is studded with glycoprotein P. = drug removal factor by hydrolysis)
The substance cannot pass through the membrane and is thrown back by hydrolysis.
Protective mechanisms.
1) Some things can be thrown away and some things can't.
2) Detoxification. Cytochrome P450 enzymes in smooth ER. Converts hydrophobic compounds to hydrophilic ones.
3) Insulation. Mitochondria without cristae. The inner membrane degrades and turns into a repository of shit. Rough XPS wraps and insulates. Nuclear shell (but not in the case of the kernel itself)
Representatives of ABC Transporters
1) MDR 1 and MDR 2
2) TAP 1 and TAP 2. Transporters associated with antigen processing.
3) STE6 for mating pheromone transport (in yeast)
4) Chlorocrine ATPase. In the membrane of the moth-like plasmodia.
5) CFTR transmembrane regulator in cystic fibrosis. Chlorine transport regulator. In the airways, sweat glands, bile ducts.
Chlorine minus + water. Liquefied secret. In pathology, chlorine is retained in the cell. Water doesn't flow. As a result, the mucous secretion thickens. medium for bacteria.
Signaling.
3) Effectors of signaling pathways.
1. Ion channels. (smell, taste) 2. Cytoskeleton (crawls, moves). 3. Components of metabolic pathways (enzymes) 4. Activation of gene regulatory proteins
There is no linear circuit. 1 receptor => signal bifurcation. But at the same time the integrative response, with multiple receptors, the response goes in one direction.
Chain interchangeability.
Receptors
Receptors associated with ion channels.
1) Acetylcholine receptor channel. 5 subunits, multi-senting structure and calcium and sodium. Fast synaptic transmission. Few mediator required. 2 alpha, beta, gamma, delta suba.
2) Receptors associated with g-proteins. 7 trans-membranes, serpentine, multispawning, the main section between the 5th and 6th chain - is associated with the g protein. (alpha-betta, gamma, subunits)
3) Catalytic receptors. Singel span structure. Powerful submembrane region with tyrosine kinase domain (catalytic activity) In lymphocytes especially important. The membrane is pierced once.
Mechanisms of switching off receptors. DESENSITIZATION
1) Sequestration of the receptor in the endosome.
2) Lysosomal degradation
3) Arrest proteins. Receptor inhibition.
4) Inactivation of the signaling protein. (not receptor)
5) Inhibitor protein, inhibit phosphorylation.
LARGE SIGNAL MOLECULES,
kinases. Phosphorylate proteins.
1) Serine-threonine.
2) Tyrosine
3) Histidine (rast, bacter is especially good)
can be
a) transmembrane
b) cytoplasmic
c) amphitropic (both there and there)
phosphorylation cascade.
PHOSPHOTASES. Removal of phosphates from kinase subcountries.
Guanyl nucleotides binding proteins.
GDP and GTP bound proteins.
1) Monomeric 1 subunits (cytoskeleton RHO, vesicle RAB transport, cytoplasm poison Ran transport)
2) Heterotrimeric 3 sub alpha and gamma have their own lipid groups. Alpha is related to gdf
Small signal molecules.
1) Calcium.
2) Cyclic nucleotides. ATP -> (adenylate cyclase) cAMP (adrenal, olfactory reception)
gtp -> cgmp (guanylate cyclase) (photoreception)
camp and cgtv = protein kinases, nucleotide dependent channels.
3) FI derivatives (inositol triphosphate)
adenylate cyclase pathway.
Regulation
1) Cholera toxin blocks the hydrolysis of GTP. There is constant work. Ion channels open and water and ions bye bye - dehydration.
2) Forskolin. Constant activation of adenylate cyclase - a lot of cAMP
3) Inhibitory pathway.
4) Desensitization of receptors. (arrests, etc.)
Phosphatidylinositol transmembrane signaling pathway.
Regulation
1) Path desensitization. Arrests…
2) Blockade by arrests
3) Chemical modification of ins p3 to remove excess phosphorus or add phosphorus with inositol three phosphates.
4) Phorbol ester directly activates protein kinase C. The use of calcium ionophores
Deposition and circulation of calcium in the cell.
1) Calcium is stored in EPS (calsequestrins and calreteculirins - calcium binding proteins)
2) Calcium is stored in the cytoplasm. Calmodulin binds calcium in the cytoplasm.
3) Michondria. In the matrix. calcium concretions.
Calcium pumping through calcium channels. Pumping out through a calcium pump. Due to the energy of hydrolysis of atf. There is also a calcium-sodium antiport in muscle cells.
When calcium enters the cell.
All cells have inositol triphosphate receptor channels. (in the reticulum), but in nerve and muscle cells there are ryanodine receptors that work along with inositol triphosphate. Serks ATPase on the EPR. (pumps into the reticulum) Calmodulins in the cytoplasm. They have 4 caramans (sites) for calcium binding. In other organisms
Aquiorin (in the intestinal tract)
Recoverin
Troponin C in muscle and non-muscle cells
Protein s100 in nerve cells and glial cells.
With an inactive state of calmodulin, he has
Hydrophilic configuration -> hydrophobic -> proisomodeist with substrate – again hydrophilic conformation
catalytic receptors. with kinase domains
Receptors for growth factors, the cascade gives a mitogenic effect - it stimulates cell mitosis.
Singel span, tyrzine kinase domains 1-2. Triggering cell proliferation and differentiation.
Tyrosine kinase cascade.
Receptors bind to growth factors.
Cytoskeleton.
1975 began to discuss.
1) Microfilament system / microfibrillary system. 7nm
Structural unit of actin. Motor proteins meosin. St. squirrel system.
Microfilaments: support, shortening, cell shape, cell movement.
2) Microtubule system / tubulin system. 20 nm diameter
Tubulins. Motor dyneins and kinesins. The system of associated proteins / MAP and TAU.
3) 10 nm intermediate filament system
4) fine thin filament 5nm. Some proteins are protists.
Microtubules = transport of vesicles, formation of cilia and flagella, formation of spindle filaments.
Intermediate filaments: support-frame.
Thin filaments = textbook
MICROFILAMENT SYSTEM.
actin filaments = microfilaments
Monomer g. (globular) Polymer - f.
two main ideas: growth due to polymerization + work with myosin (muscles)
Polymerization calcium or magnesium dependent process. In the cytosol, magnesium is fucking dead - sow magnesium binds !!!1
Assembly head to tail.
Feathered end = + = assembly
Pointed end = - = disassembly
The microfilament diameter is 7 nm. The main protein is actin. It is a monomer and a polymer.
Monomer G - 42 kDa. Globular. There are three forms. Alpha, beta, gamma actins. Alpha is muscular. Betta is non-muscular. Gamma is part of stress fibrils.
Filaments have polarity plus and minus ends.
Cortical structure of actin under the membrane - shape. Actin filaments in cilia in absorptive cells. Actin analogue in bacteria MreB
There is a pool of G actin in the cell and it should polymerize, but this does not happen because of THYMOSIN. THYMOSIN blocks the change of adenyl nucleotides or prevents actin from joining.
PROFILIN removes thymosin and allows actin to polymerize. Profilin can stimulate the exchange of adp for atp.
Actin filament stabilization and destabilization.
ADP caffeine makes filament cutting accessible. Cutting marker.
artificial stabilization.
Cytochalasin. Metabolt of fresh glebs. Sits on the plus end of the filament. From the minus comes the analysis, from the plus - assembly and lengthening the total. When seeding - disassembly of the filament.
Fallodine.
Rhodamine foladin label.
actin fragmentation. Fragmin - cuts.
Protein gelzalin - also cuts.
The mechanism of actin polymerization.
Seed proteins or polymerization initiators ARP2 and 3 proteins.
Stages of actin polymerization.
1) Formation of seeds - trimmers. Build initiation
2) Stage of elongation. Growth of actin filaments towards the tremere, globules are fused
3) Thread milling + and - ends. Due to different concentrations of globular actin, assembly and disassembly are dominated by plus and minus. How much went to the plus, so much came to the minus.
Stable cytoskeleton based on meosin filaments.
Detection of structural antibodies:
1) Monoclonal antibodies to monoglobular actin
2) We take meosin and chop off two heads with a piece of tail, heavy meromeosin remains.
Processes fibrils. Actin decarnation by heavy meromeosin.
Accessory proteins of microfibre. Systems.
Association of actin filaments with the membrane.
Vinculin protein. Binds actin filaments to the cell membrane.
Erzin, myozin, radiksin.
2 - muscular
1 - non-muscular
1) muscle poper floor musculature vertebrae and bespov and smooth muscles bespov
two-headed
2) non-muscle everywhere + smooth muscles without.
DOUBLE-HEADED or SINGLE-HEADED.
Two-headed muscular and non-muscular - traditional meosins.
Single-headed meosin is an unconventional meosin.
Meosin is a two-headed muscular type. Meosin 2 is able to form large protofibrils.
Double-headed non-muscle = same but protofibrils are much shorter.
Single-headed meosins. = binds the bundle to the membrane in the villi. (across)
Single-headed meosins provide
1) Movement of actin filaments
2) Movement of the actin filament from the minus end to the plus end
3) Bubbles with a load move along the actin filament with the help of single-headed meosin with calcium and the energy of ATP.
unconventional meosins.
Over 15 classes.
Comparative chitology of microfibrillar cytology.
1) Chloroplasts. In chloroplasts, the actin ring (surrounds) Orients towards the light source.
2) An actin ring that compresses the constrictions. During cell division.
3) In epithelial cells. Desmosomes. Intercellular contacts. Actin filaments are involved
4) Spermatozoa of galaturia. The spermatozoon has an acrosome. Under the acrosome is a fund of globular actin (pool) when receptor proteins. When triggered, explosive polymerization of G-actin begins. The membrane of the spermatozoon protrudes like a member =) based on filaments. And pierces the membrane of the egg.
5) horseshoe crabs. Actin filaments spiral. But when you need to straighten up. And lengthens. (for spermatozoa)
6) Listeria monocytogenesis. Listeriosis causes. Phagocytosed by fibroblasts. The phagosome membrane dissolves and enters the cytoplasm. It is a nucleation factor for atin filaments. Actinofilament begins to form on its tail. An outgrowth is formed. Macrophages recognize him and bite him. And then, cell by cell, it destroys each phagosome and makes invaginations there, which are attacked by the next macrophages.
7) Tryponosoma lacks fibrillar actin. There is globular but mutations do not allow polymerization. She has a microtubular cytoskeleton that performs all these functions.
Microtubule system = tubuin system of the cytoskeleton.
The main protein is tubulin. Monomeric tubulin
The tube diameter is 20 nm - 22 nm.
The tubulin homologue in pracoroth Ftsr is involved in cell division.
The statmin protein binds to tubulin dimers and prevents polymerization. Phosphorylation of statmina removes it from dimers.
The microtubule can be stabilized using the MAP protein. (analogous to tropomyosin)
catastrophins - destabilize the microtubule (pull the protofilaments into pieces)
Katanin - cuts microtubules in the area of cell centers.
TAXOL - stabilizes the microtubule (it does not cut)
Colchicine, vinblastine, vincristine.... They bind to the + end of the microtubule and contribute to its depolarization. Doesn't grow.
microtubule polarization process. We knew that in the cell center
The main property of microtubules is dynamic instability. They understand and gather.
Stable cytoskeletal systems = cilia and flagella
Basal body, axoneme. 9x3 +0 9x2+2
Stable microtubules in brain tissues. The stability of the microtubule depends on the presence of tyrosine at the end of the tubule. At the end of tyrosine - understands. In brains without tyrosine.
1) MONOCLANAL antibodies to tubulin
2) Treatment with denein from axomnemic cilia
map and tau proteins
They form outgrowths on the tubules. Provide tubular connections. Connection of tubules with other systems and organelles. Stabilization of microtubules. Tubulin with map - easier to polymerize.
Tau squirrels. Important role in the differentiation of axons and dendrites. There are blocking tau proteins, dendrites are produced and axons are not.
Motor protein and microtubule system.
1) Dineins
1. Three-headed (ciliary-flagellar) axonemes of cilia and flagella in the composition of motor handles
2. Two-headed (cytoplasmic)
2) Kinesins
Acid keratins
2) Basic and neutral keratins
3) GFCB, perefirin
4) Neurofilaments (microtubules in the CNS) alpha internexin
5) Proteins of the nuclear lamina (submembrane network) under the intranuclear membrane
6) Nestin protein. In neuroepithelial stem cells
^^ The main function is support-frame. Integration of the surface metabolic apparatus
Intermediate filament test - find the focus of the tumor (source)
SUBMEMBRANE CYTOSKELETON.
SPECTRINS of erythrocytes and others (in practice)
SUPREMEMBRANE COMPLEX OF THE CELL.
Neurons in culture.
If you make a knockout of the proteins of the cell matrix, during the differentiation of neurons, the axons into the optic nerve will not intertwine. (many neurons, their axons do not intertwine together to form the optic nerve.)
Supramembrane complex
1) Glycocalyx = carbohydrate tails
2) Overmembrane domains of membrane proteins
3) Cell adhesion molecules
a) goal-to-goal interaction
b) goal-matrix interaction.
4) Intercellular substance (cell wall of fungi, cuticle, plants, intercellular spaces)
5) Enzymes of parietal digestion
1) Proteins to which the cell is attached. Proteins of the extracellular matrix - extracellular matrix.
Fibronectin, laminin, thrombospandin, collagens.
2) Proteins of the plasma membrane, with the help of which the cells are attached either to the cell or to the matrix.
Fibronectin.
1) Soluble fibronectin (hepatocins of the liver), binding to fibrin, regulate homeostasis.
(it does not have a CE domain)
2) Insoluble. Produced by fibroblasts. There is a Tse domain. It has an RGD sequence that is recognized by the integrin receptor on the surface of the fibroblast.
Homodimer, two identical chains. There are binding sites for heparin, collagen, actin, DNA, bacterial surface, and components of the extracellular matrix of loose connective tissue.
Both forms of fibronictin are encoded by a single gene. Different proteins = as a result of splicing.
Much is produced during erbryogenesis.
Fibronectin influences cell differentiation. Without it, fibroblasts cannot synthesize collagen.
Smooth muscle cells lose their contractile apparatus.
Axons lose their ability to regular directed growth.
calcium dependent.
1) Cad Gains
2) Integrins
3) Selectins
calcium independent proteins
4) Immunoglobulin-like proteins.
Homocylic, heterophile, battleship.
Target matrix.
Heterophilic, linker.
During embryogenesis and postnatal development, molecules of different cell adhesion are synthesized.
Codeherins.
Temporarily:
Homophilic interaction, in the presence of calcium.
Constantly.
whole-whole, homophilic, with calcium. Contains desmosomes.
codherins do not participate in cell-matrix interactions.
The more calcium, the more codherins integrate with each other. A lot of calcium - a stronger interaction.
Type 1 codherins = type 1 cytoskeleton
Type 2 codherins = type 2 cytoskeleton.
Beta catenins can separate from (alpha and gamma) and diffuse into the nucleus and influencing genoregulatory proteins triggering transcription = cellular response.
Not enough actin = beta will lose weight, gene expression, tyun, tyun, tyun.
Class E codherins = epithelial cells
Codherins P = platelet granules, placenta
Codherins H = neurons, lens cells, skeletal and cardiac muscles
Codherins M = during the DEVELOPMENT of striated muscles.
Integrins.
In the system of temporary intercellular contacts.
I interact with immunogloupolins.
heterophile interactions.
sat down temporarily ^^
no permanent
cel-matrix focal contact (fibronectin)
cel-matrix (permanent) hemidesmosome.
Based on integrin proteins, a complex of binding proteins that provide polymerization
Organization of selectins.
Target-target (permanent) do not participate
cel-matrix (constant) not participating
intact matrix (temporary) not involved
Only targets are temporary. Rolling of the neutrophil in the endothelium. Responsible for short-term interactions. Heterophilic. Ligands for selectins = carbohydrate tails of proteins/lipids.
L - selectins Leukocytes with endothelium, migration of leukocytes in the tissues of the lymph node
E - selectins = on the surface of the endothelium
P = surface area of platelets and endothelial cells.
Lectins. = glycoproteins. From plant cells, proroth legumes. Affinity for specific oligosaccharides.
Phytohemagglutenin, concovanalin A. If these leuktins are used to process cells, this will cause a mitogenic effect = mitosis.
RBTL reaction.
Lymphocytes turn into lymphoblasts. There is a condensation of chromatin and the division of the lymphoblast starts. Lymphocyte = lymphoblast = plasma cells (cascade)
Membrane
Secreted
On the surface of bacteria, fungi, viruses. Prototypes of immunoglobulins.
Lectin receptors on the surface of spleen macrophages recognize abnormal sugars on the surface of erythrocytes. (when aging, for example, erythrocytes in excess of 120 days)
Calcium independent adhesion
Immunoglobulin-like adhesion.
homophilic.
Or yoke like with integrins.
Vikama x leukocyte-endothelial interaction.
And kam 1,2… T-cell endothelial interaction.
a) Temporary: codherin-codherin (calcium), integrin (alpha-betta) with immunoglobulin-like (calcium dependent) Ige like-ige like (without calcium) selectin - with carbohydrate proteins / lipids (heterophilic, calcium dependent)
b) permanent:
Tight (insulating contacts) under the microvilli. Proteins of the ocludin and claudin families. Like checkers in a taxi =) 4 on each membrane of the trans segment, which fit into each other. Like clasped hands.
Desmosomes
1 dotted 2 girdle (codherins are clustered in the membrane, the environment is in the desmogley matrix) Desmogliins and desmocolins, different types of codherins that interact with each other. In the cytoplasm of each of the cells, kotherin clustering proteins work.
Platoglobin, desmoplakin. 3 for non-septal desmosomes in one membrane there is an integral protein, in the other too, between them there is a mucopolysaccharide layer It is these contacts that are the precursors of tight junctions
PLECTINS. What a bullshit.
chemical contacts.
Plasmodesma.
Nexuses. In one cell, 6 conexins form one conexon and such crap on another cell.
2) Cell-matrix
Susbrother for the cell is fibronectin.
Filopodia and lamelopodia for feeling the substarate. The cell sits on the substrate in separate parts, and not the whole belly, touch points = focal contacts. Clustering of integrins in the membrane, (alpha-betta) Talin, vinculin, tensin, paxilin, FAK (facal adhesion kinase) To all this
a) temporary (focal contact)
b) permanent (hemidesmosome)
In the basement membrane, collagen, laminin, sits on the membrane of the alimentary cell.
A cluster of integrins connects the basement membrane and the cell. Tie on intermediate filaments in a cell with integrins and a basement membrane
The metabolic apparatus of the cell.
Compartmentalization.
The cell has a pool of ribosome subunits.
Large 60S
In general 80s
rRNA - 18S, 28S,5,8S 5 S + proteins
Cytosolic ribosomes / attached ribosomes (sitting on the ER)
As soon as the ribosomes finish their activity, the subunits disintegrate.
When translation begins, the protein rarely cleaves itself (only short ones) fold chaperone proteins (folding)
If the chaperones have worked and the protein has not formed, the chaperones can unweave it and fold it again, if it fails again, then protein degradation occurs.
When the cell is thermally affected, poofing occurs - individual parts are looped out and heat shock proteins are synthesized = head shock proteins. = they are stress proteins. Their synthesis under pressure, oxidizers, heavy metals. At the same time and during normal life, they are also synthesized.
Hydrophobic regions of proteins emerge when heat treatment(exposed to the outside) these areas process heat shock proteins and, due to ATP, make a “massage”
Chaperones:
1) Prevent improper folding of proteins
2) Spread squirrels (unfolding)
3) They work both during protein synthesis and after translation.
4) Control the transport of the protein to the desired organelle
5) Participate in indirect endocytosis.
Shapernoy hsp 70 (work alone)
Chaperonins hsp 60
Powered by ATP
In 15% of cases, hsp 70 works first, then hsp 60
In 80% of cases, only chaperones work.
They are localized in the EPS, in the matrix of some organelles (chloroplasts, mitochondria), the cytosol.
The principle of operation of chaperonins.
Transport streams.
mRNA from the nucleus to the cytosol.
Small and large subunits of ribosomes unite.
each protein has a signal sequence if the sorting signal means - nuclear protein, cytosol protein, chloroplast/mitochondrial protein, perixisomes, some lysosomes. So the broadcast is going on. And the ribosome will be free (cytosolic.
protein, EPS, secret, Golgi, Lysosomes, plasma membranes. TO is arrested for elogation, the ribosome is transplanted to the ER, and translation goes to the ER. After translation, the subunits separate.
There are three main types of protein transport
1) Nuclear plasma transport. Squirrels go into a folded state.
2) Post-translational transport to membrane organelles (also the first story) Mitochondria, chloroplasts, perixisomes
3) vesicular transport. Co-translational transfer of proteins into the ER and then vesicular transport of proteins through the ER and Golgi (mandatory)
Protein sorting.
Each protein has its own addressing.
1) Signal in a protein molecule (where to go)
2) A receptor in the organelle (recognizes the signal sequence) or a shuttle protein that recognizes the signal sequence.
3) Protein translocation system in the organelle membrane (translocom)
4) Energy source.
Sorting signals:
1) Signal sequence. At the H-terminus, from 15 to 60 amino acids.
2) Signal plaque (signal patch) several signal sequences in structure, after folding these sequences are stacked side by side - signal plaque.
3) Signal anchors. (single or many) = transmembrane domains = signal anchors (eg protein channels) Top start signal (top membrane) bottom stop transfer. at each transmembrane site.
4) Protein retention signals = retention signal. The protein remains inside the organelle and does not go anywhere (EPR, golgi) KDEL in eps.
5) Destruction box = area of destruction, when the protein is folded, the destruction box is hidden. As soon as the protein folds properly, the destruction box is exposed.
Protein degradation. The structure of the proteasome.
Not only lysosomes, but also proteosomes degrade proteins.
Initially, it was believed that only cyclins are degraded in proteasomes.
After that, it was understood that most endogenous cellular proteins are degraded in proteasomes.
And in lysosomes, proteins from the outside.
But the lysosome eats its own mitochondria.
Proteosam. 26S she has 2 caps. (2 caps) weighing 19s but immune proteasomes, presentation of viral antigens, they have caps 11s. Under the caps there is an ATP ring, between them there are 4 rings of 7 subunits. It's all part of crop caps = 20s
Destruction boxing is recognized by ubiquetins. There are 3 types of enzymes that do this.
E1 = conservative = ubictivin activating
E2 = variable 3 types: conjugate, adjoin each other E1 = ubiquiten tree
E3 = ubiquitin ligators recognize boxing.
The lid opens (cap), the aphasic base removes ubiquitin, the protein unfolds, enters the chamber, with the cap closing, after which the protease activity of the beta rings is turned on. Amino acids are gradually cut off. And throw out short peptides or amino acids. Next to it are aminopeptidases that convert peptides to amino acids.
In immunoproteasomes, the same is true, but there peptides of 10-12 amino acids from the cap grab the carriers, and drag them to the shEPS where they are waiting for MChS1, and in the ABC membrane, the transporters tap 1 and tap 2. And landing on the MChS1 molecule, then on the golge, then a bubble, then presentation to lymphocytes.
degraded in the proteasome
1) Misfolded proteins
2) Damaged proteins
3) Excess unnecessary proteins
4) Incorrectly chemically modified proteins
5) Cyclins
Smooth (agrunular) Intertwining trunks, butular structure, one membrane. Biosynthesis of membrane lipids, hormones (thyroid) detoxification of harmful substances - cytochrome p450, calcium depot
Rough (granular)
Ribosome. The broadcast is on. The signal peptide is synthesized.
The signal sequence is recognized by SRP - signal recognition particle. 11s in it 7s PHA and proteins that work in pairs, 9 and 14 kDa + 68 and 72 kDa + 19 and 54 kDa. Often referred to as SRP 54. That is, it has 6 proteins
54 is usually associated with Gdf. The whole thing recognizes the signal. Gdf changes to gtf. Arrest for elongation. The broadcast freezes. The whole complex is moored to a rough EPS. There is a lumen. And the protein complex is a translocome. The ribosome sits on the translock.
Beta subunit in the membrane, alpha on beta in plasma. = CRP receptor. It weighs 72 kDa. On its alpha subunit, GDP. As soon as this complex recognizes the SRP, GDP moves into the cytosol with the alpha subunit and sits with GTP. The receptor through alpha interacts with 54. (which is also GTP) As soon as the GAP factor works at both sites of GTP, GTP is hydrolyzed in both sites. The ribosome lands on the translocon and sits on the ER. Choperons accompany. Next comes the dissociation of the CRP particle. The CRP receptor enters the membrane. The elongation arrest is lifted.
Translocon = protein complex responsible for the transfer of proteins into the eps. Consists of several proteins
SEC 61 SEC 63 and others. 3, 4 protein complexes which consist of 3 transmembrane domains. They function in the idea of two halves according to EPS.
Translocon does
!) Recognizes the target (ribosomes) of the polypeptide chain
2) Binding of the ribosome and its orientation on the translocon
3) Embedding an extended chain
4) Translocation and pause in translocation
5) ? translocon or not is not known. Addition of lipids to the synthesized protein.
6) ? adding a GPI anchor to the synthesized protein (inositol)
7) Glycosylation = addition of carbohydrate tree
8) The work of signal peptidases to cut off signal sequences
9) folding (folding)
10) Translocon permeability control
11) Final fold and protein release
12) Quality control. Control over a long elongated chain and over the acquisition of the necessary modifications by the protein.
13) Protein retrotranslocation and subsequent degradation.
Translocon = protein complex. There is a cover. It looks like a channel. This is where the ribosome sits.
CRP leaves, the channel opens, the broadcast is on.
Translocation of proteins into ER.
1) If the protein is translucent
2) If the membrane protein is associated (singal span)
3) multispan squirrels. There is a translation on the eps membrane, a protein in the membrane, there is a stop transfer. Further sections with stops and starts
Protein modifications in EPS. As soon as the signal sequence appeared and the protein went. Co-translational modifications = formation of disulfide bonds this is what disulfide bond isomerase does = it is a luminal resident.
2) Glycosylation. Glycosidases and glycosyltransferases = eps residents
3) Folding (folding) chaperones. Inside the eps make BiP proteins.
4) optional modification adding GUI (anchor)
5) optional modification by adding lipids
Proteins that are permanently present in the membrane or lumen of the eps = resident proteins.
Resident proteins have a retention signal = retention signal. For translucent residents, this is the KDEL signal. For membrane residents = KXKX
Next to translocons 2 residents = calmyxin, calreticulin. (calcium binding)
As soon as a carbohydrate tree is hung on the synthesized protein, calmexin binds the protein with a leptin bond. Calmexin - synthesized protein (per carbohydrate) Grabs it.
If the protein is mowing, then it is outweighed by calreticulin and there unfolding, deglycosylation and re-folding, glycolysis if cheers = then ok. Release signal.
If not, then after the ribosome has left, the translocon opens and through a special subunit responsible for retrotranslation, the shitty protein is thrown into the cytosol of the EPS and there the ubiquitins are piled in the cytosol of the EPS where proteosomes sit .. ERAD system
Protein glycosylation. All squirrels
n-glycosylation = starts in the ER and ends in the golgi, or completely in the ER. Suspension of asparagine to nh2 groups.
O-glycosylation attaches to the side chains of he groups of serine and threonine. Usually occurs in the golgi.
1) Glycocalyx carbohydrates. Intercellular communication reception
2) Glycosylation is necessary in folding.
3) Stabilization of the protein molecule after translation.
H-glycosylation is co-translational (jointly)
O-glycosylation is post-translational.
Glycosylation of proteins in the EPS is drawn.
Golgi apparatus. Organization Options
1) Cisternal = cisterns + bubbles
2) Tubular = tubules + vesicles
3) Vesicular = large blisters + blisters.
IN vitro.
Tanks interact with each other. + Necessarily bubbles between tanks.
Three flows of proteins through the golgi
1) Lysosomal hydrolases. Synthesis on the ER and pass through the Golgi (all cells)
2) The flow of proteins and lipids to the plasma membrane - constitutive secretion. Goes constantly without special signals (all cells)
3) Only for secretory cells. regulated secretion. Regulation - through the concentration of calcium.
Transport via bubble shuttles. between each tank.
Ascending transport (eps - goldi - golgi cisterns) - anterograde.
Return transport from any Goolji department. - retrograde
matrix of the golgi apparatus. Cytosol golgi apparatus there are special UDF - activated sugar
1) End of glycosylation (functions)
2) o-glycosylation.
3) Plant cell - the formation of a cell wall.
4) Modification (phosphorylation) of lysosomal hydrolases. go through phosphorylation steps
5) Sulfation of some proteins
6) Proteolysis of some proteins
7) The final folding of those proteins that did not have time to form in the ER (did not finish)
8) Formation of primary lysosomes.
Post-translational transport of lysosomal hydrolases.
ER with ribosomes -> translation
In the cis golgi network and in the cis cisterns, the final modification of the hydrolase takes place.
There are lysosomal storage diseases. More than 40 diseases. Mutation in the gene for the manose-6-phosphate receptor. Or a mutation in lysomal hydrolases.
In the first beam, lysomal hydrolases follow a different path and are secreted from the cell.
In the second case, lysomal hydrolases do not work.
As a result, lysosomes are filled with undigested substances - inclusion cells (inclusions) - diseases of the accumulation of undigested residues.
2 hypotheses of the organization of the Golgi apparatus
1) Hypothesis of stable compartments (the Golgi apparatus consists of stable tanks and networks and intermediaries - bubbles)
2) Hypothesis of maturation. All tanks can mature and move from one to another. Bubbles eps, give cis, then copper, then trance, then bubbles.
The presence of rescue cisterns (tubular-vesicular cluster) is not always present. Apparently depends on the intensity of synthesis.
In the cis regions, phosphorylation of lysomal hydrols, and removal of manoses from some hydrolases
In the medial section, removal of manoses and removal of GlcNAC
In the trans divisions, the addition of galactose and n-acetylneuraminic (sialic acid)
sulfation of some proteins takes place in the network and distribution over three 3 then.
Glycosylation of proteins in the Golgi apparatus.
At the exit from the Golgi, 3 variants of organization are possible: 3 manoses + 2 GlcNac = constant.
1) 2 GlcNac 2 Gal 2 Nana + const
2) Asparagine on it + const + (hybrid version)
3) Asparagine + const + 6 manose
Stages of formation of complex sugars.
Asparagine + five-membered cor + 5 manoz on top. (starting version from EPS) 1) Monosidase 1 removes 3 manoses = asparagine + five-membered core + 2 manoses on the left and 0 on the right. 2) 1 UDP activated GlcNac (glcNac - transferase) = five-membered root on asparagine, 2 manoses on the left and glcNac stands on the right
3) manosidase 2 removes 2 manoses on the left. = aspargin + core + GlcNac 4) 1 UPD GlcNAc – transferase 2.
as a result, aspargin + core + GlcNac + GlcNac. These are the medial
In trans departments
5) 2 udp activated galactoses (galactosyl transferase) = 5 member core on asparagine, where 2 GlcNac sit on them two galactoses (Gal) 6) sialic acid transferase plants 2 nana. (n-acetyl neurominic acids)
Glycolipids (cerebrosides and gangliosides) Ceramides - smooth eps and the golgi apparatus hangs trees)
Transport of proteins in mitochondria.
Synthesis of most mitochondrial proteins on free ribosomes. Mitochondrial signaling signals. (multiple signals to multiple mitochondrial membranes) chaperones recognize signals
Non-woven proteins are fed to areas where both membranes are very close (inner and outer)
Inner membrane translocators (TOM) (intermembrane) and translocators (TIM) of the outer membrane (matrix)
1) Signal = mitochondrial
2) 2 signals = one for one membrane, another for the second
3 signals
Transfer of perexisomal proteins. = single-membrane organelle. (see green tutorial)
peroxisomes = oxidation. Inside it, hydrogen peroxide = oxidation. Catalase provides water and oxygen.
Many peroxisomes in the kidneys and liver.
Peroxisomes are divided by constriction. Enzymes form a crystalloid on electrons.
Cytosolic ribosomes synthesize proteins. PTS is a signal at the end of peroxoso proteins.
Chaperones fold proteins with PTS. Shuttle proteins recognize - peroxins. Per 5 per 7 they bring this complex to the perexisomes. The peroxosome contains a peroxin receptor. The receptor recognizes that through a special translocon - peroxisomes (8 proteins), the entire complex of peroxins and protein enters the matrix of the peroxisomes. The protein remains there, and the shuttle returns to the cytosol again.
Molecular mechanisms of vesicular transport in the cell.
1) Donor compartments (bud off)
2) Shipping container (vial or tube)
3) Acceptor compartment (perceives the load)
4) Must be microtubule rails or microfilaments
The load must be selected. To do this, proteins have sorting signals.
2) It is necessary to form a container (vesicles or tubules) for this, adapter proteins are needed that will recognize receptors and pubescence proteins are needed.
3) It is necessary to protractor vesicle of dyneinin, unconventional myosin
4) Target recognition. Tetaring factors. (far proximity factors)
5) Mooring to the target (docking) or anchoring
6) Merging with the target (fusion)
Protein fusions provide docking and fusion
2 main routes of vesicular transport.
Hair proteins and adapter leucorrhoea.
pubescence
Clathrin 70
Coatomeric proteins = Cop proteins. (in the Eps and Golgi region) 80 years
90 years of Copa 1 and Copa 2
In the area of the beginning of 2000. We found caveolin (caveolin pubescence (cholestrol transport)
Clathrin. Structural unit 3 skeleton. 3 chains of 190kDa (heavy) = 3 light
Proteins of assembly of clathrin pubescence (atp nada) (polymerization) depolymerization = undressing atphase, removes clathrin.hsp 70
Receptor-mediated endocytosis (found clathrin)
The terminal section of the golgi network (there clathrins) during the final maturation of the vesicle.
Adapter proteins (adaptins) open 4 classes of adapter proteins AP 1 2 3 b 4
Ap 1 in netvor golgi. Ap 2 - transport going with receptors from the plasma membrane.
2 heavy chains. Alpha and beta. Each 100 kDa + one 50 kDa medium chain + one small chain = delta chain. It weighs 17 kDA. The middle chain learns the sorting sequence.
Further, the dynamin protein separates the transport container from the membrane.
There are areas without ribosomes in SHEPs - exit zones
sorting in golgi
1) Based on signal sequences
2) based on patches (plaques)
3) according to physical and chemical properties - lipids and proteins
Exocytosis.
TGN (network)
1) Lysosomal enzymes (hydrolases)
2) Constitutive secretion = the flow of proteins and lipids, glyco, in a membrane-associated state, occurs in all cells, occurs constantly and does not depend on signals
3) Regulated secretion. Secretory proteins, in the secretory cells, in the cavity of the vesicle, the vesicles descended by clathrin plaques (patch) depart. GTP phase ARF1 is needed to regulate the landing of the omission. vesicles, v and t SNARE ;lth;fn uhfyeks calcium activates anexin protein, activation of SNAP and H + incorporation of RAB and release of contents outside the cell.
Endocytosis. It happens different. Types of endocytosis
1) Phagocytosis
2) Pincocytosis
3) Receptor-mediated endocytosis
4) Transcytosis.
Receptor mediated (clathrin endocytosis)
Receptor - growth factor
The receptor is a hormone
antigen - antibody
The most important property of this transport is the specificity
Heterophagy (absorption of substances from outside) and autophagy (absorption of own spent structures)
Mitochondria for example.
g EPS either or
Wrap around mitochondria autophagic vacuole (fusion with lysosome)
Lysosomal enzymes are mostly formed in sEPS and further in the Golgi
Some enzymes synthesize the KFERQ signal (apinopeptidase) on free cytosolic ribosomes.
Chaperones fold proteins with such a signal, and this complex is recognized by the receptor, and then immersion occurs inside the translocon.
Lysosomes can take up some proteins from the cytosol on their own (enzymes)
Phagocyto and pinocytosis.
Phagocytosis is the absorption of particles of a sufficiently large size. absorption by the receptor. But not specific.
2 models of phagocytosis
Pseudopodia. The contact of the phagocytureme of the particle and the membrane is complete. A la lightning.
Pinocytosis = fine particles or liquid components. Maybe no receptors. = non-specific.
Pinocytic canals with pinosomes.
Transcytosis (diacytosis) absorption on the apical part of the cell. Transport without change to the basal and release from the cell.
Cell cycle. Mitosis.
Stage of cell life from one division to another
Interphase.
G1 = 2n2c = postmitotic, presynthetic. 30-40% cell life
С = 2n4c synthetic period. 50% life
Yg2 = 10% postsynthetic (premitotic)
Cell division.
Direct (amitosis) Division without cytokinesis. Hepatocytes
Indirect. Meiosis. reduction division.
in embryogenesis. Cell cycle = s -> mitosis. Other stages pass quickly.
In g1, cell growth and the establishment of an adult nuclear and cytoplasmic ratio. Increased biosynthetic processes, translation and transcription, signaling, secretion, etc. Cell life.
G0 terminal = cardiomyocytes and most neurons (for a long time in w0)
In zh0 transcription, translation occurs at an average level (stable, not intensive) in zh0 the size is less than zh1. The size of the nucleus is slightly smaller, the chromatin is slightly more condensed, and there are fewer chromosomes. less RNA. From x0 the cell can go further into the cycle.
CHECK points in cycles.
Mitosis. Metaphase check point. J1. C. g2. Zh1 checkpoint. Zh1S checkpoint - at the transition. G2 checkpoint.
Biochemistry control system for cell cycle passage.
x1 checkpoint = how much the cell has grown and check the organoid.
w1c = replication or w0. Check for this
F2 = strand break test, DNA repair. Check before the start of mitosis.
Regulation of the cell cycle.
Cyclin dependent kinase CDK.
Protein cyclins
A complex of cyclins and their corresponding kinases. during the life of the cell. During life there is a complex, during the transition from phase to phase, the dissociation of the complex occurs. Inactivation of cyclin dependent kinases through dephosphorylation
Ubequentinated by cyclin
whole divisional cycle - genes. These genes fluctuate in expression
J1 period. SDK delta type kinase 4 type
G2 type 2 kinase type 2
beta type of cyclins. 8 types
Cell division.
prometaphase
metaphase
Anaphase a
anaphase b
Anything above karyokinesis
Telovaza
Cytokinesis goes along with telophase.
Anaphase a - the movement of chromatin towards the poles.
Prophase of methosis.
Chromatin is compacted in chromosomes. Laying. A sharp decrease in transcriptional activity. nucleolus inactivation. Under the nuclear envelope, lamina proteins are phosphorylated. Lamin B remains bound to the nuclear envelope. And the nuclear envelope is fragmented into vesicles. Golgi and eps are also fragmented into vesicles
Prometaphase.
On the basis of cytoplasmic microtubules, the drift of doubled chromatids occurs, with the help of motor proteins, the doubled chromatids move along the microtubules, the nuclear membrane is no longer there. Drift along microtubules to the poles, as soon as the tubules reach the cell centers, they turn over and, due to the growth of new microtubules, begin to be pushed to the center.
Metaphase.
There are 2 cell centers at the poles. (non-membrane organelles
2 perpendicular to the centriole. 9 triplets on the periphery and 0 in the center. A B C tubes. A = 13 rows of tubulins. B and C 15 tubulins each.
A and B = beta tubulin. C = delta tubulin.
Centrine proteins
Centriolar fibrillar protein halo of thin filaments near the centriole. Microtubules emerge from this. A new centriole is formed on the basis of the maternal one. And on the basis of the daughter, the formation of a new maternal takes place. It takes place in the S period.
In the maternal region, gamma tubulin ring complexes are primers for the formation of spindle microtubules.
Astral microtubules = in different directions.
Interpolar microtubules = from pole to pole but not all the way.
Chromosomal (kinetachore) go to each of the sister chromatids.
It is necessary to give, to get and to be reciprocated correctly.
Chromosomes in equatorial = mitophase plate. Chepoint. SDC and cyclins. Destruction of the nuclear envelope, compaction of chromosomes, assembly of the fission spindle
When moving from meta to annas. APC/s begins to work ubiquitinization of the cyclin complex and proteasomal degradation. Transition to anaphase A.
A kinetochore is formed in the region of the primary constrictions of chromosomes.
The nucleus is a compartment for separating hereditary information from the rest of the cytoplasm.
The compartment is separated by a double membrane.
And in the core one can distinguish
Nuclear envelope - 2 membranes
Chromatin
Karyoplasm
protein bodies.
Nuclear protein matrix.
Nuclear envelope 2 membranes, they are of different quality.
Outer - with ribosomes and it goes into the sEPR
Internally associated with lamina densae proteins (lamins)
These two membranes fuse in the region of the core complex.
The nuclear membrane can form invaginations or invaginations - increase the area. (transport intensification)
The space between the two membranes is the perinuclear space.
Its volume increases if the outer membrane grows. In these swellings are various inclusions(e.g. starch granules, endobionts of BACTERIA! %)
The structure of nuclear pores is conservative in all eukaryotes.
The model object of the nucleus is xenopus frog oocytes.
The number of pores is dynamic. Intensive synthesis - a lot of pores. There is little synthesis - there are few pores.
The nuclear pore complex consists of 3 rings that are put on one axis - coaxial rings
In the center there are looped domains that form a tangled ball; at the moment of passing the load, this ball unwinds and facilitates the passage of the load.
Time from proteins nucleoparins. About 30 nucleo-pairs in yeasts and up to 100 in vertebrates.
3 classes of nucleoparins:
1) peripheral proteins associated with curved filaments or a cytoplasmic ring, they have a beta propeller and often carry oligosaccharides. If we treat a living cell with lectins, then transport through the nucleus is blocked
2) Nucleoparins having a large transmembrane domain, they anchor the pore complex in the membrane.
3) Nucleoparins that carry the FG repeat (phenyalanine and glycine), these repeats, about 40 of them, create tracks (rails), carrier proteins bind to them, and thanks to this binding, cargo is transported. Transporters can use the same nucleoporins. There is a whole series of connections with FG repeats.
Chromatin is attached to lamin proteins anchored on the inner membrane.
The work of the pores depends on the concentration of calcium. With a lot - it's time to open. With little - closed.
Antibodies to nucleoparins - will stop all transport.
Nuclear cytoplasmic transport is very intense. More than 1 million macromolecules are transported. Per second.
Proteins that are less than 45kDA are able to freely diffuse between the nucleus and the cytoplasm, and this diffusion is not disturbed even when the temperature drops to 4 degrees.
This is passive diffusion.
Molecules over 45 kDa for such molecules, the temperature must be above 4 degrees, this is an energy-dependent process and must be observed.
Import (path to kernel)
Export (from kernel)
Carrier proteins are importins. Export - exportins. Then these proteins are united into one group - kareoferrens.
3 terms of transport. Import.
1) The protein that must enter the nucleus must carry a nuclear signaling signal.
2) The presence of careoferin (importin) is required
3) There should be a concentration gradient of small GTPase Ran
The RAn gtp and gdp gradient is needed so that karyopherins can crawl back out and repeat the cycle.
The nuclear nucleus of xenopus oocytes isolated the nucleopsame protein, this protein is a pentamer and it has a multiple signal of nuclear expulsion, if this signal is cut off, then nucleoplasmin does not enter the nucleus. If this signal is attached to a protein that has nothing to do in the nucleus, then the protein will still get into the nucleus.
Immune gold method. Mark signal sequences with gold.
The nuclear alarm signal does not CUT, unlike other signals.
When disassembling the nuclear membrane during mitosis, 2 cells and, possibly, the protein will have to be fed into the nucleus again, and the signal has already been sewn into it, and so - oops.
Kareopherin beta 2, signal and import and export.
beta 3 and beta 4 carry ribosomal proteins.
Export. First time observed. Export of mRNA on the transcription product of insect salivary glands.
mRNA transport. Tightly rolled tape, unfolds at one end and crawls through the pore. Forward goes 5 strokes with the end. At the 3rd stroke, the end of the temporary contact with the nucleoparins of the ring keeps the posterior end in the nucleus to the end, until the end it checks whether the transcript is correct.
This RNA must be associated with proteins that will carry out transport - exportins, these proteins carry the export signal. Still need a Ran GTP gradient. That is, both Ran GTP and expotin proteins sit on RNA.
Squirrels are shuttles with signals for both import and export.
Proteins can get out on RNA (riding a pig) protein without a signal and associated with RNA is transported into the cytoplasm).
Histone and non-histone proteins.
There are two states of chromtain.
Euhramotin - active transprit
Heterochromatin is compact and inactive.
Heteroromatin is constitutive, always compartmentalized and never involved in transcription, and facultative heterochramtin which is included in transcription.
Constitutive chromatin is up to 15% in the human genome and up to 35% in the fruit fly genome. There are highly repetitive sequences. This is satellite DNA. This DNA is present on telomeric and recentromeric regions. The constitutive is often associated with the periphery of the nucleus, it has a number of properties. - replicates late in the S phase, it is sticky, thanks to it, conjugation occurs, but there is no crossing-over specifically there. Silangsing. Silences nearby genes.
Quite quickly, it is known that the main proteins that make up chromosomes are HISTONES.
Histnons
H1 H2A H2b H3 H4 are highly conserved proteins. The difference in 1 a.k. in the city and thymus piglet.
Histone fold - 3 alpha helices.
H1 - the most enriched with lysine
h2 and h2b - moderately enriched with lysine
h3 and h4 - arginine.
h1 can be replaced by h5
Sometimes histones can be replaced by protamines.
Histone to DNA ratio = 1:1
Histone coat model. A histone coat envelops the DNA thread from all sides, then this thread twists along with this coat.
This model did not reflect the diffraction pattern + during long-term treatment with nuclease, chromatin resolved into segments that are multiple in length, for example, 100 base pairs each, but no less.
Archaea have histones, but there is a different order of histone assembly.
Bacteria do not have histones, DNA is assembled by Hu protein
Dinoflagellates, there is a lot of DNA in the nucleus, but there are no histones. Secondary loss of histones. Secondary lost nucleosomes. DNA is embedded in a liquid crystal. The rest have nucleosomes.
Nucleosomes are the first level of chromatin packaging.
Histone H1 packs into the second level. It binds to the nucleosome.
American school. = solinoid model.
Level 3 compartmentalization 300nm.
Abbreviations
TAG - triacylglycerols
PL - phospholipids C - cholesterol
cxc - free cholesterol
eCS - esterified cholesterol PS - phosphatidylserine
PC - phosphatidylcholine
PEA - phosphatidylethanolamine FI - phosphatidylinositol
MAG - monoacylglycerol
DAG - diacylglycerol PUFA - polyunsaturated fatty acids
fatty acids
XM - chylomicrons LDL - low density lipoproteins
VLDL - very low density lipoproteins
HDL - high density lipoproteins
LIPID CLASSIFICATION
The possibility of classifying lipids is difficult, since the class of lipids includes substances that are very diverse in structure. They are united by only one property - hydrophobicity.
STRUCTURE OF INDIVIDUAL REPRESENTATIVES OF LI-PIDS
Fatty acid
Fatty acids are part of almost all of these classes of lipids,
except for derivatives of CS.
Human fat fatty acids are characterized by the following features:
an even number of carbon atoms in the chain,
no chain branching
the presence of double bonds only in cis-conformations
in turn, the fatty acids themselves are heterogeneous and differ long
chain and quantity double bonds.
TO rich fatty acids include palmitic (C16), stearic
(C18) and arachidic (C20).
TO monounsaturated- palmitoleic (С16:1), oleic (С18:1). These fatty acids are found in most dietary fats.
Polyunsaturated fatty acids contain 2 or more double bonds,
separated by a methylene group. In addition to differences in quantity double bonds, acids differ in their position relative to the beginning of the chain (denoted by
cut the Greek letter "delta") or the last carbon atom of the chain (denoted
letter ω "omega").
According to the position of the double bond relative to the last carbon atom, the polyline
saturated fatty acids are divided into
ω-6-fatty acids - linoleic (C18:2, 9.12), γ-linolenic (C18:3, 6,9,12),
arachidonic (С20:4, 5,8,11,14). These acids form vitamin F, and co-
held in vegetable oils.
ω-3-fatty acids - α-linolenic (C18: 3, 9,12,15), timnodonic (eicoso-
pentaenoic, C20;5, 5,8,11,14,17), klupanodone (docosapentaenoic, C22:5,
7,10,13,16,19), cervonic (docosahexaenoic, C22:6, 4,7,10,13,16,19). Nai-
a more significant source of acids of this group is the fat of cold fish
seas. An exception is α-linolenic acid, found in hemp.
nom, linseed, corn oils.
Role of fatty acids
It is with fatty acids that the most famous function of lipids is associated - energy
getic. Thanks to the oxidation of fatty acids, body tissues receive more
half of all energy (see β-oxidation), only erythrocytes and nerve cells do not use them in this capacity.
Another and very important function of fatty acids is that they are a substrate for the synthesis of eicosanoids - biologically active substances that change the amount of cAMP and cGMP in the cell, modulating the metabolism and activity of both the cell itself and surrounding cells. . Otherwise, these substances are called local or tissue hormones.
Eicosanoids include oxidized derivatives of eicosotrienoic (C20:3), arachidonic (C20:4), timnodonic (C20:5) fatty acids. They cannot be deposited, they are destroyed within a few seconds, and therefore the cell must constantly synthesize them from incoming polyene fatty acids. There are three main groups of eicosanoids: prostaglandins, leukotrienes, thromboxanes.
Prostaglandins (Pg) - are synthesized in almost all cells, except for erythrocytes and lymphocytes. There are types of prostaglandins A, B, C, D, E, F. Functions prostaglandins are reduced to a change in the tone of the smooth muscles of the bronchi, genitourinary and vascular systems, gastrointestinal tract, while the direction of changes is different depending on the type of prostaglandins and conditions. They also affect body temperature.
Prostacyclins are a subtype of prostaglandins (PgI) , but additionally have a special function - they inhibit platelet aggregation and cause vasodilation. Synthesized in the endothelium of the vessels of the myocardium, uterus, gastric mucosa.
Thromboxanes (Tx) formed in platelets, stimulate their aggregation and
called vasoconstriction.
Leukotrienes (Lt) synthesized in leukocytes, in the cells of the lungs, spleen, brain
ha, hearts. There are 6 types of leukotrienes A, B, C, D, E, F. In leukocytes, they
stimulate cell motility, chemotaxis, and cell migration to the focus of inflammation; in general, they activate inflammation reactions, preventing its chronicity. Cause co-
contraction of the muscles of the bronchi in doses 100-1000 times less than histamine.
Addition
Depending on the initial fatty acid, all eicosanoids are divided into three groups:
First group – formed from linoleic acid in accordance with the number of double bonds, prostaglandins and thromboxanes are assigned an index
1, leukotrienes - index 3: for example,Pg E1, Pg I1, Tx A1, Lt A3.
It's interesting thatPGE1 inhibits adenylate cyclase in adipose tissue and prevents lipolysis.
Second group synthesized from arachidonic acid according to the same rule, it is assigned an index of 2 or 4: for example,Pg E2, Pg I2, Tx A2, Lt A4.
Third group eicosanoids are derived from thymnodonic acid, by number
double bonds are assigned indices 3 or 5: for example,Pg E3, Pg I3, Tx A3, Lt A5
The subdivision of eicosanoids into groups is of clinical importance. This is especially pronounced in the example of prostacyclins and thromboxanes:
|
Initial |
Number |
Activity |
Activity | |||
|
oily |
double bonds | |||||
|
prostacyclins |
thromboxanes | |||||
|
acid |
in a molecule | |||||
|
γ - Linolenova | ||||||
|
i C18:3, | ||||||
|
Arachidonic | ||||||
|
Timnodono- |
increase |
descending | ||||
|
activity |
activity | |||||
The resulting effect of the use of more unsaturated fatty acids is the formation of thromboxanes and prostacyclins with a large number of double bonds, which shifts the rheological properties of the blood to a decrease in viscosity.
bones, lowering thrombosis, dilates blood vessels and improves blood
tissue supply.
1. Researchers' attention to ω -3 acids attracted the phenomenon of the Eskimos, co-
indigenous inhabitants of Greenland and the peoples of the Russian Arctic. Against the background of a high consumption of animal protein and fat and a very small amount of vegetable products, they had a number of positive features:
no incidence of atherosclerosis, ischemic disease
heart and myocardial infarction, stroke, hypertension;
increased content of HDL in blood plasma, a decrease in the concentration of total cholesterol and LDL;
reduced platelet aggregation, low blood viscosity
a different fatty acid composition of cell membranes compared to the European
mi - S20:5 was 4 times more, S22:6 16 times!
This state is calledANTIATHEROSCLEROSIS .
2. Besides, in experiments to study the pathogenesis of diabetes mellitus it was found that prior applicationω -3 fatty acids pre-
prevented death in experimental ratsβ -cells of the pancreas when using alloxan (alloxan diabetes).
Indications for useω -3 fatty acids:
prevention and treatment of thrombosis and atherosclerosis,
diabetic retinopathy,
dyslipoproteinemia, hypercholesterolemia, hypertriacylglycerolemia,
myocardial arrhythmias (improvement in conduction and rhythm),
peripheral circulatory disorders
Triacylglycerols
Triacylglycerols (TAGs) are the most abundant lipids in
human body. On average, their share is 16-23% of the body weight of an adult. TAG functions are:
reserve energy, the average person has enough fat reserves to support
life activity during 40 days of complete starvation;
heat-saving;
mechanical protection.
Addition
An illustration of the function of triacylglycerols are the care requirements
premature babies who have not yet had time to develop a fatty layer - they need to be fed more often, take additional measures against hypothermia of the baby
The composition of TAG includes the trihydric alcohol glycerol and three fatty acids. Fat-
nye acids can be saturated (palmitic, stearic) and monounsaturated (palmitoleic, oleic).
Addition
An indicator of the unsaturation of fatty acid residues in TAG is the iodine number. For a person, it is 64, for creamy margarine 63, for hemp oil - 150.
By structure, simple and complex TAGs can be distinguished. In simple TAGs, everything is fat-
nye acids are the same, for example, tripalmitate, tristearate. In complex TAGs, fat-
nye acids are different, : dipalmitoyl stearate, palmitoyl oleyl stearate.
Rancidity of fats
Rancidity of fats is a household term for lipid peroxidation, which is widespread in nature.
Lipid peroxidation is a chain reaction in which
the formation of one free radical stimulates the formation of other free radicals
ny radicals. As a result, polyene fatty acids (R) form their hydroperoxides(ROOH). Antioxidant systems counteract this in the body.
we, including vitamins E, A, C and enzymes catalase, peroxidase, superoxide
dismutase.
Phospholipids
Phosphatic acid (PA)- intermediate co-
unity for the synthesis of TAG and PL.
Phosphatidylserine (PS), phosphatidylethanolamine (PEA, cephalin), phosphatidylcholine (PC, lecithin)–
structural PL, together with cholesterol form a lipid
bilayer of cell membranes, regulate the activity of membrane enzymes and membrane permeability.
Besides, dipalmitoylphosphatidylcholine, being
surfactant, serves as the main component surfactant
lung alveoli. Its deficiency in the lungs of preterm infants leads to the development of syn-
droma of respiratory failure. Another function of FH is its participation in education. bile and maintaining the cholesterol in it in a dissolved
Phosphatidylinositol (FI) plays a key role in phospholipid-calcium
mechanism of hormonal signal transduction into the cell.
Lysophospholipids is a product of hydrolysis of phospholipids by phospholipase A2.
Cardiolipin a structural phospholipid in the mitochondrial membrane Plasmalogens-participate in the construction of the structure of membranes, up to
10% phospholipids of the brain and muscle tissue.
Sphingomyelins Most of them are located in the nervous tissue.
EXTERNAL LIPIDS METABOLISM.
The lipid requirement of an adult organism is 80-100 g per day, of which
vegetable (liquid) fats should be at least 30%.
Triacylglycerols, phospholipids and cholesterol esters come with food.
Oral cavity.
It is generally accepted that lipids are not digested in the mouth. However, there is evidence of infant secretion of tongue lipase by Ebner's glands. Lingual lipase secretion is stimulated by sucking and swallowing movements during breastfeeding. This lipase has an optimum pH of 4.0-4.5, which is close to the pH of the gastric contents of infants. It is most active against milk TAGs with short and medium fatty acids and ensures the digestion of about 30% of emulsified milk TAGs to 1,2-DAG and free fatty acid.
Stomach
Own lipase of the stomach in an adult does not play a significant role in the
lipid digestion due to its low concentration, the fact that its optimum pH is 5.5-7.5,
lack of emulsified fats in food. In infants, gastric lipase is more active, since in the stomach of children the pH is about 5 and milk fats are emulsified.
Additionally, fats are digested due to the lipase contained in milk ma-
teri. Lipase is absent in cow's milk.
However, the warm environment, gastric peristalsis causes emulsification of fats, and even low active lipase breaks down small amounts of fat,
which is important for the further digestion of fats in the intestines. The presence of a mini-
a small amount of free fatty acids stimulates the secretion of pancreatic lipase and facilitates the emulsification of fats in the duodenum.
Intestines
Digestion in the intestine is carried out under the influence of pancreatic
lipases with an optimum pH of 8.0-9.0. It enters the intestine in the form of prolipase, pre-
rotating into an active form with the participation of bile acids and colipase. Colipase, a trypsin-activated protein, forms a complex with lipase in a 1:1 ratio.
acting on emulsified food fats. As a result,
2-monoacylglycerols, fatty acids and glycerol. Approximately 3/4 TAG after hydro-
lysis remain in the form of 2-MAG and only 1/4 of the TAG is completely hydrolyzed. 2-
MAGs are absorbed or converted by monoglyceride isomerase to 1-MAG. The latter is hydrolyzed to glycerol and fatty acids.
Up to 7 years, the activity of pancreatic lipase is low and reaches a maximum by
pancreatic juice also has an active
trypsin-induced phospholipase A2 has been found
phospholipase C and lysophospholipase activity. The resulting lysophospholipids are ho-
roshim surfactant, so
mu they contribute to the emulsification of dietary fats and the formation of micelles.
intestinal juice has phospho-
lipases A2 and C.
Phospholipases require Ca2+ ions to help remove
fatty acids from the catalysis zone.
Hydrolysis of cholesterol esters is carried out by cholesterol-esterase of pancreatic juice.
Bile
Compound
Bile is alkaline. It produces a dry residue - about 3% and water -97%. In the dry residue, two groups of substances are found:
sodium, potassium, creatinine, cholesterol, phosphatidylcholine that got here by filtering from the blood
bilirubin, bile acids actively secreted by hepatocytes.
Normally, there is a ratio bile acids : FH : XC equal 65:12:5 .
about 10 ml of bile per kg of body weight is formed per day, thus, in an adult it is 500-700 ml. Bile formation is continuous, although the intensity fluctuates sharply throughout the day.
The role of bile
Along with pancreatic juice neutralization sour chyme, I act
scoop from the stomach. At the same time, carbonates interact with HCl, carbon dioxide is released and the chyme is loosened, which facilitates digestion.
Provides fat digestion
emulsification for subsequent exposure to lipase, a combination is necessary
nation [bile acids, unsaturated acids and MAGs];
reduces surface tension, which prevents the droplets of fat from draining;
the formation of micelles and liposomes that can be absorbed.
Thanks to paragraphs 1 and 2, it ensures the absorption of fat-soluble vitamins.
Excretion excess cholesterol, bile pigments, creatinine, metals Zn, Cu, Hg,
medicines. For cholesterol, bile is the only route of excretion, 1-2 g / day is excreted.
Bile acid formation
The synthesis of bile acids occurs in the endoplasmic reticulum with the participation of cytochrome P450, oxygen, NADPH and ascorbic acid. 75% cholesterol formed in
The liver is involved in the synthesis of bile acids. Under experimental hypovitami-
nose C guinea pigs have developed except for scurvy atherosclerosis and gallstone disease. This is due to the retention of cholesterol in cells and a violation of its dissolution in
bile. Bile acids (cholic, deoxycholic, chenodeoxycholic) are synthesized
are in the form of paired compounds with glycine - glyco derivatives and with taurine - tauro derivatives, in a ratio of 3: 1, respectively.
enterohepatic circulation
This is the continuous secretion of bile acids into the intestinal lumen and their reabsorption in the ileum. There are 6-10 such cycles per day. Thus,
a small amount of bile acids (only 3-5 g) ensures digestion
lipids received during the day.
Violation of bile formation
Violation of bile formation is most often associated with a chronic excess of cholesterol in the body, since bile is the only way to remove it. As a result of a violation of the ratio between bile acids, phosphatidylcholine and cholesterol, a supersaturated solution of cholesterol is formed from which the latter precipitates in the form gallstones. In addition to the absolute excess of cholesterol in the development of the disease, the lack of phospholipids or bile acids plays a role in the violation of their synthesis. Stagnation in the gallbladder, which occurs with malnutrition, leads to thickening of bile due to the reabsorption of water through the wall, lack of water in the body also exacerbates this problem.
It is believed that 1/3 of the world's population has gallstones, by old age these values reach 1/2.
Interesting data on the ability of ultrasound to detect
gallstones in only 30% of cases.
Treatment
Chenodeoxycholic acid at a dose of 1 g / day. Causes a decrease in cholesterol deposition
dissolution of cholesterol stones. Pea-sized stones without bilirubin layers
ny dissolve within six months.
Inhibition of HMG-S-CoA reductase (lovastatin) - reduces synthesis by 2 times
Adsorption of cholesterol in gastrointestinal tract(cholestyramine resins,
Questran) and preventing its absorption.
Suppression of the function of enterocytes (neomycin) - a decrease in the absorption of fats.
Surgical removal of the ileum and termination of reabsorption
bile acids.
lipid absorption.
Happens in upper section small intestine in the first 100 cm.
short fatty acids absorbed without any additional mechanisms, directly.
Other components form micelles with hydrophilic and hydrophobic
layers. The size of micelles is 100 times smaller than the smallest emulsified fat droplets. Through the aqueous phase, micelles migrate to the brush border of the mucosa.
shells.
Regarding the mechanism of lipid absorption itself, there is no well-established idea. First point vision lies in the fact that micelles penetrate inside
whole cells by diffusion without energy expenditure. Cells break down
micelles and the release of bile acids into the blood, FA and MAG remain and form TAG. By another point vision, micelles are taken up by pinocytosis.
And finally Thirdly, it is possible to penetrate into the cell only lipid com-
components, and bile acids are absorbed in the ileum. Normally, 98% of dietary lipids are absorbed.
Digestion and absorption disorders may occur
in liver disease and gallbladder, pancreas, intestinal wall,
damage to enterocytes with antibiotics (neomycin, chlortetracycline);
excess calcium and magnesium in water and food, which form bile salts, interfering with their function.
Lipid resynthesis
This is the synthesis of lipids in the intestinal wall from post-
exogenous fats sold here, endogenous fatty acids can also be partially used.
When synthesizing triacylglycerols received
fatty acid is activated through the addition of co-
enzyme A. The resulting acyl-S-CoA is involved in the synthesis of triacylglycemic
reads in two possible ways.
First way–2-monoacylglyceride, occurs with the participation of exogenous 2-MAH and FA in the smooth endoplasmic reticulum: a multienzyme complex
triglyceride synthase forms TAG
In the absence of 2-MAG and a high content of fatty acids, second way,
glycerol phosphate mechanism in the rough endoplasmic reticulum. The source of glycerol-3-phosphate is the oxidation of glucose, since dietary glycerol
roll quickly leaves the enterocytes and goes into the blood.
Cholesterol is esterified using acylS- CoA and AChAT enzyme. Reesterification of cholesterol directly affects its absorption into the blood. At present, possibilities are being sought to suppress this reaction in order to reduce the concentration of cholesterol in the blood.
Phospholipids are resynthesized in two ways - using 1,2-MAH for the synthesis of phosphatidylcholine or phosphatidylethanolamine, or through phosphatidic acid in the synthesis of phosphatidylinositol.
Lipid transport
Lipids are transported in the aqueous phase of the blood as part of special particles - li-poproteins.The surface of the particles is hydrophilic and is formed by proteins, phospho-lipids and free cholesterol. Triacylglycerols and cholesterol esters make up the hydrophobic core.
The proteins in lipoproteins are commonly referred to as apoproteins, several of their types are distinguished - A, B, C, D, E. In each class of lipoproteins there are corresponding apoproteins that perform structural, enzymatic and cofactor functions.
Lipoproteins differ in the ratio
niyu triacylglycerols, cholesterol and its
esters, phospholipids and as a class of complex proteins consist of four classes.
chylomicrons (XM);
very low density lipoproteins (VLDL, pre-β-lipoproteins, pre-β-LP);
low density lipoproteins (LDL, β-lipoproteins, β-LP);
high density lipoproteins (HDL, α-lipoproteins, α-LP).
Transport of triacylglycerols
Transport of TAGs from the intestines to tissues is carried out in the form of chylomicrons, from the liver to tissues - in the form of very low density lipoproteins.
Chylomicrons
general characteristics
formed in intestines from resynthesized fats
they contain 2% protein, 87% TAG, 2% cholesterol, 5% cholesterol esters, 4% phospholipids. Os-
the new apoprotein is apoB-48.
are normally not detected on an empty stomach, appear in the blood after a meal,
coming from the lymph through the thoracic lymphatic duct, and completely disappeared
yut after 10-12 hours.
not atherogenic
Function
Transport of exogenous TAGs from the intestine to tissues that store and use
stinging fats, mainly world
tissue, lungs, liver, myocardium, lactating mammary gland, bone
brain, kidney, spleen, macrophages
Disposal
On the endothelium of the capillaries above
listed tissues is fer-
cop lipoprotein lipase, attach-
attached to the membrane by glycosaminoglycans. It hydrolyzes TAG, which are part of chylomicrons to free
fatty acids and glycerol. Fatty acids move into the cells, or remain in the blood plasma and, in combination with albumin, are carried with the blood to other tissues. Lipoprotein lipase is able to remove up to 90% of all TAGs located in the chylomicron or VLDL. After finishing her work residual chylomicrons fall into
liver and are destroyed.
Very low density lipoproteins
general characteristics
synthesized in liver from endogenous and exogenous lipids
8% protein, 60% TAG, 6% cholesterol, 12% cholesterol esters, 14% phospholipids The main protein is apoB-100.
normal concentration is 1.3-2.0 g/l
slightly atherogenic
Function
Transport of endogenous and exogenous TAGs from the liver to tissues that store and use
using fats.
Disposal
Similar to the situation with chylomicrons, in tissues they are exposed to
lipoprotein lipase, after which the residual VLDL is either evacuated to the liver or converted into another type of lipoprotein - low-
which density (LDL).
MOBILIZATION OF FAT
IN resting state liver, heart, skeletal muscle and other tissues (except
erythrocytes and nervous tissue) more than 50% of energy is obtained from the oxidation of fatty acids coming from adipose tissue due to background TAG lipolysis.
Hormone dependent activation of lipolysis
At voltage organism (starvation, prolonged muscular work, cooling
ing) hormone-dependent activation of TAG lipase occurs adipocytes. Except
TAG-lipases, in adipocytes there are also DAG- and MAG-lipases, the activity of which is high and constant, but at rest it is not manifested due to the lack of substrates.
As a result of lipolysis, free glycerol And fatty acid. Glycerol transported in the blood to the liver and kidneys here is phosphorylated and converted to the glycolysis metabolite glyceraldehyde phosphate. Depending on the us-
lovium GAF can be involved in gluconeogenesis reactions (during starvation, muscle exercise) or oxidized to pyruvic acid.
Fatty acid transported in complex with plasma albumin
at physical activity- in muscles
during starvation - in most tissues and about 30% are captured by the liver.
During fasting and physical exertion after penetration into the cells, fatty acids
slots enter the β-oxidation pathway.
β - fatty acid oxidation
β-oxidation reactions occur
mitochondria in most cells of the body. For oxidation use
fatty acids coming
cytosol from the blood or with intracellular lipolysis of TAG.
Before penetrating into the mat-
mitochondrial rix and be oxidized, the fatty acid must activate-
Xia.This is done by attaching
with coenzyme A.
Acyl-S-CoA is a high-energy
genetic connection. Irreversible
the reaction is achieved by hydrolysis of diphosphate into two molecules
phosphoric acid
Acyl-S-CoA synthetases are located
in the endoplasmic reticulum
IU, on the outer membrane of mitochondria and inside them. There are a number of synthetases specific to different fatty acids.
Acyl-S-CoA is not capable of passing
blow through the mitochondrial membrane
brane, so there is a way to transfer it in combination with vitamins
like substance carnity-
nom.There is an enzyme on the outer membrane of mitochondria carnitine-
acyl transferaseI.
After binding to carnitine, the fatty acid is transported through
translocase membrane. Here, on the inside of the membrane, fer-
cop carnitine acyl transferase
II
re-forms acyl-S-CoA which
enters the path of β-oxidation.
The process of β-oxidation consists of 4 reactions, repeated cyclically
Czech. They successively
there is oxidation of the 3rd carbon atom (β-position) and as a result from fat-
acid, acetyl-S-CoA is cleaved off. The remaining shortened fatty acid returns to the first
reactions and everything repeats again, until
until two acetyl-S-CoA are formed in the last cycle.
Oxidation of unsaturated fatty acids
When unsaturated fatty acids are oxidized, the cell needs
additional enzyme isomerases. These isomerases move double bonds in fatty acid residues from γ- to β-position, transfer natural double bonds
connections from cis- V trance-position.
Thus, the already existing double bond is prepared for β-oxidation and the first reaction of the cycle, in which FAD is involved, is skipped.
Oxidation of fatty acids with an odd number of carbon atoms
Fatty acids with an odd number of carbons enter the body with plants.
body food and seafood. Their oxidation occurs in the usual way to
the last reaction in which propionyl-S-CoA is formed. The essence of the transformations of propionyl-S-CoA is reduced to its carboxylation, isomerization and formation
succinyl-S-CoA. Biotin and vitamin B 12 are involved in these reactions.
Energy balance β -oxidation.
When calculating the amount of ATP formed during β-oxidation of fatty acids, it is necessary
take into account
number of β-oxidation cycles. The number of β-oxidation cycles can be easily represented based on the idea of a fatty acid as a chain of two-carbon units. The number of breaks between units corresponds to the number of β-oxidation cycles. The same value can be calculated using the formula n / 2 -1, where n is the number of carbon atoms in the acid.
the amount of acetyl-S-CoA formed is determined by the usual division of the number of carbon atoms in the acid by 2.
the presence of double bonds in fatty acids. In the first reaction of β-oxidation, the formation of a double bond occurs with the participation of FAD. If there is already a double bond in the fatty acid, then this reaction is not necessary and FADH2 is not formed. The remaining reactions of the cycle go without changes.
the amount of energy used to activate
Example 1 Oxidation of palmitic acid (C16).
For palmitic acid, the number of β-oxidation cycles is 7. In each cycle, 1 FADH2 molecule and 1 NADH molecule are formed. Entering the respiratory chain, they will "give" 5 ATP molecules. In 7 cycles, 35 ATP molecules are formed.
Since there are 16 carbon atoms, 8 molecules of acetyl-S-CoA are formed during β-oxidation. The latter enters the TCA, when it is oxidized in one turn of the cycle
la formed 3 molecules of NADH, 1 molecule of FADH2 and 1 molecule of GTP, which is equivalent to
Lente 12 ATP molecules. Only 8 molecules of acetyl-S-CoA will provide the formation of 96 ATP molecules.
There are no double bonds in palmitic acid.
1 molecule of ATP goes to activate the fatty acid, which, however, is hydrolyzed to AMP, that is, 2 macroergic bonds are spent.
Thus, summing up, we get 96 + 35-2 = 129 ATP molecules.
Example 2 Oxidation of linoleic acid.
The number of acetyl-S-CoA molecules is 9. So 9×12=108 ATP molecules.
The number of cycles of β-oxidation is 8. When calculating, we get 8×5=40 ATP molecules.
An acid has 2 double bonds. Therefore, in two cycles of β-oxidation
2 FADH 2 molecules are not formed, which is equivalent to 4 ATP molecules. 2 macroergic bonds are spent on the activation of a fatty acid.
Thus, the energy yield is 108+40-4-2=142 ATP molecules.
Ketone bodies
Ketone bodies include three compounds of similar structure.
The synthesis of ketone bodies occurs only in the liver, the cells of all other tissues
(except erythrocytes) are their consumers.
The stimulus for the formation of ketone bodies is the intake of a large amount
fatty acids to the liver. As already mentioned, under conditions that activate
lipolysis in adipose tissue, about 30% of the formed fatty acids are retained by the liver. These conditions include starvation, type I diabetes mellitus, prolonged
nye physical activity, a diet rich in fats. Also, ketogenesis is enhanced by
catabolism of amino acids related to ketogenic (leucine, lysine) and mixed (phenylalanine, isoleucine, tyrosine, tryptophan, etc.).
During starvation, the synthesis of ketone bodies is accelerated by 60 times (up to 0.6 g / l), with diabetes mellitusItype - 400 times (up to 4 g / l).
Regulation of fatty acid oxidation and ketogenesis
1. Depends on the ratio insulin/glucagon. With a decrease in the ratio, lipolysis increases, the accumulation of fatty acids in the liver increases, which are actively
act in the reaction of β-oxidation.
With the accumulation of citrate and high activity of ATP-citrate-lyase (see below), the resulting malonyl-S-CoA inhibits carnitine acyl transferase, which prevents
contributes to the entry of acyl-S-CoA into mitochondria. Molecules present in the cytosol
acyl-S-CoA cells go to the esterification of glycerol and cholesterol, i.e. for the synthesis of fats.
In case of violation of the regulation malonyl-S-CoA synthesis is activated
ketone bodies, since the fatty acid that has entered the mitochondria can only be oxidized to acetyl-S-CoA. Excess acetyl groups are forwarded for synthesis
ketone bodies.
STORAGE OF FAT
Lipid biosynthesis reactions take place in the cytosol of the cells of all organs. Substrate
for the synthesis of fats de novo is glucose, which, entering the cell, is oxidized along the glycolytic pathway to pyruvic acid. Pyruvate in mitochondria is decarboxylated to acetyl-S-CoA and enters the TCA cycle. However, at rest,
rest, in the presence of a sufficient amount of energy in the cell of the TCA reaction (particularly
ity, isocitrate dehydrogenase reaction) are blocked by excess ATP and NADH. As a result, the first metabolite of TCA, citrate, is accumulated, moving into cy-
tozol. Acetyl-S-CoA formed from citrate is further used in biosynthesis
fatty acids, triacylglycerols and cholesterol.
Biosynthesis of fatty acids
The biosynthesis of fatty acids occurs most actively in the cytosol of liver cells.
nor, intestines, adipose tissue at rest or after eating. Conventionally, 4 stages of biosynthesis can be distinguished:
Formation of acetyl-S-CoA from glucose or ketogenic amino acids.
Transfer of acetyl-S-CoA from mitochondria to the cytosol.
in complex with carnitine, as well as higher fatty acids are transferred;
usually in the composition of citric acid, formed in the first reaction of the TCA.
Citrate coming from mitochondria is cleaved in the cytosol by ATP-citrate-lyase to oxaloacetate and acetyl-S-CoA.
Formation of malonyl-S-CoA.
Synthesis of palmitic acid.
It is carried out by a multi-enzymatic complex "fatty acid synthase" which includes 6 enzymes and an acyl-carrying protein (ACP). The acyl-carrying protein includes a derivative of pantothenic acid, 6-phosphopane-tetheine (PP), which has an SH group, similar to HS-CoA. One of the enzymes of the complex, 3-ketoacyl synthase, also has an SH group. The interaction of these groups determines the beginning of the biosynthesis of fatty acids, namely palmitic acid, which is why it is also called "palmitate synthase". Synthesis reactions require NADPH.
In the first reactions, malonyl-S-CoA is sequentially attached to the phospho-pantetheine of the acyl-carrying protein and acetyl-S-CoA to the cysteine of 3-ketoacyl synthase. This synthase catalyzes the first reaction, the transfer of an acetyl group.
py on C2 malonyl with the elimination of the carboxyl group. Further into the keto group, the reaction
reduction, dehydration and again reduction turns into methylene with the formation of saturated acyl. Acyl transferase transfers it to
cysteine of 3-ketoacyl synthase and the cycle is repeated until a palmitic residue is formed.
new acid. Palmitic acid is cleaved off by the sixth enzyme of the complex, thioesterase.
Fatty acid chain elongation
Synthesized palmitic acid, if necessary, enters the endo-
plasma reticulum or mitochondria. With the participation of malonyl-S-CoA and NADPH, the chain is extended to C18 or C20.
Polyunsaturated fatty acids (oleic, linoleic, linolenic) can also elongate with the formation of eicosanoic acid derivatives (C20). But double
ω-6-polyunsaturated fatty acids are synthesized only from the corresponding
predecessors.
For example, when forming ω-6 fatty acids of the series, linoleic acid (18:2)
dehydrogenates to γ-linolenic acid (18:3) and elongates to eicosotrienoic acid (20:3), the latter is further dehydrogenated to arachidonic acid (20:4).
For the formation of ω-3-series fatty acids, for example, timnodonic (20:5), it is necessary
The presence of α-linolenic acid (18:3) is expected, which dehydrates (18:4), lengthens (20:4) and dehydrates again (20:5).
Regulation of fatty acid synthesis
There are the following regulators of fatty acid synthesis.
Acyl-S-CoA.
first, by the principle of negative feedback inhibits the enzyme acetyl-S-CoA carboxylase, preventing the synthesis of malonyl-S-CoA;
Secondly, it suppresses citrate transport from mitochondria to cytosol.
Thus, the accumulation of acyl-S-CoA and its inability to react
esterification with cholesterol or glycerol automatically prevents the synthesis of new fatty acids.
Citrate is an allosteric positive regulator acetyl-S-
CoA carboxylase, accelerates the carboxylation of its own derivative - ace-tyl-S-CoA to malonyl-S-CoA.
covalent modification-
tion acetyl-S-CoA carboxylase by phosphorylation-
dephosphorylation. Participate- 
cAMP-dependent protein kinase and protein phosphatase. Insu-
lin activates the protein
phosphatase and promotes the activation of acetyl-S-CoA-
carboxylase. Glucagon And address
naline by adenylate cyclase mechanism cause inhibition of the same enzyme and, consequently, of all lipogenesis.
SYNTHESIS OF TRIACYLGLYCEROLS AND PHOSPHOLIPIDS
General principles of biosynthesis
The initial reactions for the synthesis of triacylglycerols and phospholipids coincide and
occur in the presence of glycerol and fatty acids. As a result, synthesized
phosphatidic acid. It can be converted in two ways - CDF-DAG or dephosphorylated to DAG. The latter, in turn, is either acylated to
TAG, or binds to choline and forms PC. This PC contains saturated
fatty acid. This pathway is active in the lungs, where dipalmitoyl-
phosphatidylcholine, the main substance of the surfactant.
CDF-DAG, being the active form of phosphatidic acid, then turns into phospholipids - PI, PS, PEA, PS, cardiolipin.
At first glycerol-3-phosphate is formed and fatty acids are activated
Fatty acid coming from the blood at
the breakdown of HM, VLDL, HDL or synthesized in
cell de novo from glucose should also be activated. They are converted to acyl-S-CoA in ATP-
dependent reaction.
Glycerolin the liver is activated in the phosphorylation reaction using macroergic
ATP phosphate. IN muscles and adipose tissue this react-
cation is absent, therefore, in them, glycerol-3-phosphate is formed from dihydroxyacetone phosphate, a metabolite
glycolysis.
In the presence of glycerol-3-phosphate and acyl-S-CoA, phosphatidic acid.
Depending on the type of fatty acid, the resulting phosphatidic acid
If palmitic, stearic, palmitooleic, oleic acids are used, then phosphatidic acid is directed to the synthesis of TAG,
In the presence of polyunsaturated fatty acids, phosphatidic acid is
phospholipid precursor.
Synthesis of triacylglycerols
Biosynthesis of TAG liver increases under the following conditions:
a diet rich in carbohydrates, especially simple ones (glucose, sucrose),
an increase in the concentration of fatty acids in the blood,
high concentrations of insulin and low concentrations of glucagon,
the presence of a source of "cheap" energy, such as ethanol.
Synthesis of phospholipids
Biosynthesis of phospholipids compared with the synthesis of TAG has significant features. They consist in additional activation of PL components -
phosphatidic acid or choline and ethanolamine.
1. Activation choline(or ethanolamine) occurs through the intermediate formation of phosphorylated derivatives, followed by the addition of CMP.
In the next reaction, activated choline (or ethanolamine) is transferred to DAG
This pathway is characteristic of the lungs and intestines.
2. Activation phosphatidic acid consists in joining the CMF to it with
Lipotropic substances
All substances that promote the synthesis of PL and prevent the synthesis of TAG are called lipotropic factors. These include:
Structural components of phospholipids: inositol, serine, choline, ethanolamine, polyunsaturated fatty acids.
The donor of methyl groups for the synthesis of choline and phosphatidylcholine is methionine.
Vitamins:
B6, which promotes the formation of PEA from PS.
B12 and folic acid involved in the formation of the active form of metio-
With a lack of lipotropic factors in the liver, fatty infiltrate
walkie-talkie liver.
DISORDERS OF TRIACYLGLYCEROL METABOLISM
Fatty infiltration of the liver.
The main cause of fatty liver is metabolic block synthesis of VLDL. Since VLDL include heterogeneous compounds, the block
can occur at different levels of synthesis.
Apoprotein synthesis block - lack of protein or essential amino acids in food,
exposure to chloroform, arsenic, lead, CCl4;
block in the synthesis of phospholipids - the absence of lipotropic factors (vitamins,
methionine, polyunsaturated fatty acids);
assembly block of lipoprotein particles under the influence of chloroform, arsenic, lead, СCl4;
blocking the secretion of lipoproteins into the blood - СCl4, active peroxidation
lipids in case of deficiency of the antioxidant system (hypovitaminosis C, A,
There may also be a deficiency of apoproteins, fofolipids with a relative
excess substrate:
synthesis of an increased amount of TAG with an excess of fatty acids;
synthesis of an increased amount of cholesterol.
Obesity
Obesity is an excess of neutral fat in subcutaneous fat.
fiber.
There are two types of obesity - primary and secondary.
primary obesity is a consequence of hypodynamia and overeating.
In the body, the amount of food absorbed is regulated by the adipocyte hormone
leptin.Leptin is produced in response to an increase in fat mass in the cell
and ultimately reduces education neuropeptide Y(which encourages
search for food, and vascular tone and blood pressure) in the hypothalamus, which suppresses the food habit
denie. In 80% of obese individuals, the hypothalamus is insensitive to leptin. 20% have a defect in the structure of leptin.
Secondary obesity- occurs with hormonal diseases. To such
diseases include hypothyroidism, hypercortisolism.
A typical example of low pathogenic obesity is boron obesity.
sumo wrestlers. Despite the obvious excess weight, the sumo masters for a long time
They enjoy relatively good health due to the fact that they do not experience physical inactivity, and weight gain is associated exclusively with a special diet enriched with polyunsaturated fatty acids.
DiabetesIItype
The main cause of type II diabetes mellitus is a genetic predisposition
Presence - in relatives of the patient, the risk of getting sick increases by 50%.
However, diabetes will not occur unless there is a frequent and/or prolonged increase in blood glucose, which occurs when overeating. In this case, the accumulation of fat in the adipocyte is the "desire" of the body to prevent hyperglycemia. However, further insulin resistance develops, since the inevitable changes
adipocyte changes lead to disruption of insulin binding to receptors. At the same time, background lipolysis in the overgrown adipose tissue causes an increase
concentration of fatty acids in the blood, which contributes to insulin resistance.
Increasing hyperglycemia and insulin release lead to increased lipogenesis. Thus, two opposite processes - lipolysis and lipogenesis - enhance
and cause the development of type II diabetes mellitus.
The activation of lipolysis is also facilitated by the often observed imbalance between the intake of saturated and polyunsaturated fatty acids, so
how a lipid droplet in an adipocyte is surrounded by a monolayer of phospholipids, which must contain unsaturated fatty acids. In violation of the synthesis of phospholipids, the access of TAG-lipase to triacylglycerols is facilitated and their
hydrolysis is accelerated.
CHOLESTEROL METABOLISM
Cholesterol belongs to a group of compounds that have
based on a cyclopentanperhydrophenanthrene ring, and is an unsaturated alcohol.
Sources
Synthesis in the body is about 0.8 g/day,
while half of it is formed in the liver, about 15% in
intestine, the remainder in any cells that have not lost the nucleus. Thus, all body cells are capable of synthesizing cholesterol.
Of the foods richest in cholesterol (in terms of 100 g
product):
sour cream 0.002 g
butter 0.03 g
eggs 0.18 g
beef liver 0.44 g
whole day with food comes in on average 0,4 G.
Approximately 1/4 of the total cholesterol in the body is esterified polyne-
saturated fatty acids. In blood plasma, the ratio of cholesterol esters
to free cholesterol is 2:1.
breeding
Removal of cholesterol from the body occurs almost exclusively through the intestines:
with faeces in the form of cholesterol and neutral sterols formed by the microflora (up to 0.5 g / day),
in the form of bile acids (up to 0.5 g / day), while some of the acids are reabsorbed;
about 0.1 g is removed with the exfoliating epithelium of the skin and the secretion of the sebaceous glands,
approximately 0.1 g is converted into steroid hormones.
Function
Cholesterol is the source
steroid hormones - sex and adrenal cortex,
calcitriol,
bile acids.
In addition, it is a structural component of cell membranes and contributes
ordering into a phospholipid bilayer.
Biosynthesis
Occurs in the endoplasmic reticulum. The source of all carbon atoms in the molecule is acetyl-S-CoA, which comes here as part of citrate, as well as
in the synthesis of fatty acids. Cholesterol biosynthesis consumes 18 molecules
ATP and 13 NADPH molecules.
The formation of cholesterol occurs in more than 30 reactions, which can be grouped
feast in several stages.
Synthesis of mevalonic acid
Synthesis of isopentenyl diphosphate.
Synthesis of farnesyl diphosphate.
Synthesis of squalene.
Synthesis of cholesterol.
regulation of cholesterol synthesis
The main regulatory enzyme is hydroxymethylglutaryl-S-
CoA reductase:
firstly, according to the principle of negative feedback, it is inhibited by the final product of the reaction -
cholesterol.
Secondly, covalent
modification with hormonal
nal regulation: insu-
lin, by activating protein phosphatase, promotes
enzyme transition hydro-
hydroxy-methyl-glutaryl-S-CoA reductase into active
state. Glucagon and hell
renaline through the adenylate cyclase mechanism
ma activate protein kinase A, which phosphorylates the enzyme and translates
it to inactive form.
Transport of cholesterol and its esters.
Carried out by low and high density lipoproteins.
low density lipoproteins
general characteristics
Formed in the liver de novo and in the blood from VLDL
composition: 25% proteins, 7% triacylglycerols, 38% cholesterol esters, 8% free cholesterol,
22% phospholipids. The main apo protein is apoB-100.
normal content in the blood 3.2-4.5 g / l
the most atherogenic
Function
Transport XC into cells that use it for synthesis reactions of sex hormones (sex glands), gluco- and mineralocorticoids (adrenal cortex),
lecalciferol (skin), utilizing cholesterol in the form of bile acids (liver).
Transport of polyene fatty acids in the form of cholesterol esters in
some cells of loose connective tissue - fibroblasts, platelets,
endothelium, smooth muscle cells,
epithelium of the glomerular membrane of the kidneys,
bone marrow cells,
corneal cells,
neurocytes,
basophils of the adenohypophysis.
The peculiarity of this group of cells is the presence of lysosomal acidic hydrolase, decomposing cholesterol esters. Other cells do not have such enzymes.
On cells that use LDL, there is a high-affinity receptor specific for LDL - apoB-100 receptor. When LDL interacts with the receptor,
lipoprotein endocytosis and its lysosomal breakdown into its constituent parts - phospholipids, amino acids, glycerol, fatty acids, cholesterol and its esters.
Cholesterol is converted into hormones or incorporated into membranes. Excess membranes-
many cholesterol are removed with the help of HDL.
Exchange
In the blood, they interact with HDL, giving free cholesterol and receiving esterified cholesterol.
Interact with apoB-100 receptors in hepatocytes (about 50%) and tissues
(about 50%).
high density lipoproteins
general characteristics
are formed in the liver de novo, in blood plasma during the breakdown of chylomicrons, some
the second amount in the intestinal wall,
composition: 50% protein, 7% TAG, 13% cholesterol esters, 5% free cholesterol, 25% PL. The main apoprotein is apo A1
normal content in the blood 0.5-1.5 g / l
antiatherogenic
Function
Transport of cholesterol from tissues to the liver
A donor of polyenoic acids for the synthesis of phospholipids and eicosanoids in cells
Exchange
The LCAT reaction actively proceeds in HDL. In this reaction, the unsaturated fatty acid residue is transferred from PC to free cholesterol with the formation of lysophosphatidylcholine and cholesterol esters. Losing the phospholipid membrane HDL3 is converted into HDL2.
Interacts with LDL and VLDL.
LDL and VLDL are a source of free cholesterol for the LCAT reaction, in exchange they receive esterified cholesterol.
3. Through specific transport proteins, it receives free cholesterol from cell membranes.
3. Interacts with cell membranes, gives away part of the phospholipid shell, thus delivering polyene fatty acids to normal cells.
CHOLESTEROL METABOLIC DISORDERS
Atherosclerosis
Atherosclerosis is the deposition of cholesterol and its esters in the connective tissue of the walls
arteries, in which the mechanical load on the wall is expressed (in descending order
actions):
abdominal aorta
coronary artery
popliteal artery
femoral artery
tibial artery
thoracic aorta
thoracic aortic arch
carotid arteries
Stages of atherosclerosis
Stage 1 - damage to the endothelium.This is the "dolipid" stage, it is found
even in one year olds. Changes in this stage are nonspecific and can be caused by:
dyslipoproteinemia
hypertension
increased blood viscosity
viral and bacterial infections
lead, cadmium, etc.
At this stage, zones of increased permeability and adhesiveness are created in the endothelium.
bones. Outwardly, this manifests itself in loosening and thinning (up to the disappearance) of the protective glycocalyx on the surface of endotheliocytes, expansion of the interendo-
telial fissures. This leads to an increase in the release of lipoproteins (LDL and
VLDL) and monocytes in the intima.
Stage 2 - the stage of initial changes observed in most children and
young people.
Damaged endothelium and activated platelets produce inflammatory mediators, growth factors, and endogenous oxidants. As a result, monocytes penetrate even more actively through the damaged endothelium into the intima of the vessels and
contribute to the development of inflammation.
Lipoproteins in the area of inflammation are modified by oxidation, glycosylation
ion, acetylation.
Monocytes, transforming into macrophages, absorb altered lipoproteins with the participation of "junk" receptors (scavenger receptors). The fundamental moment
The fact is that the absorption of modified lipoproteins goes without participation
apo-B-100 receptors, and, therefore, UNREGULATED ! In addition to macrophages, this way lipoproteins also enter smooth muscle cells, which are massively transferred
go into a macrophage-like form.
Accumulation of lipids in cells quickly exhausts the low capacity of cells to utilize free and esterified cholesterol. They are overflowing with
roids and turn into foamy cells. Externally on the endothelium appear whether-
Pimples and stripes.
Stage 3 - the stage of late changes.It is characterized by the following features
Benefits:
accumulation outside the cell of free cholesterol and esterified linoleic acid
(that is, as in plasma);
proliferation and death of foam cells, accumulation of intercellular substance;
cholesterol encapsulation and fibrous plaque formation.
Outwardly, it manifests itself as a protrusion of the surface into the lumen of the vessel.
Stage 4 - stage of complications.At this stage,
plaque calcification;
plaque ulceration leading to lipid embolism;
thrombosis due to platelet adhesion and activation;
vessel rupture.
Treatment
In the treatment of atherosclerosis, there should be two components: diet and medications. The goal of treatment is to reduce the concentration of total plasma cholesterol, LDL and VLDL cholesterol, increase HDL cholesterol.
Diet:
Food fats should include equal proportions of saturated, monounsaturated
polyunsaturated fats. The proportion of liquid fats containing PUFAs should be
at least 30% of all fats. The role of PUFAs in the treatment of hypercholesterolemia and atherosclerosis is reduced to
limited absorption of cholesterol in the small intestine
activation of bile acid synthesis,
decrease in the synthesis and secretion of LDL in the liver,
increase in HDL synthesis.
It has been established that if the ratio Polyunsaturated fatty acids equals 0.4, then
Saturated fatty acids
consumption of cholesterol in an amount up to 1.5 g per day does not lead to hypercholesterolemia
rolemia.
2. Consumption of high amounts of vegetables containing fiber (cabbage, sea-
cow, beet) to enhance intestinal motility, stimulate bile secretion and adsorption of cholesterol. In addition, phytosteroids competitively reduce cholesterol absorption,
however, they are not absorbed by themselves.
Sorption of cholesterol on fiber is comparable to that on special adsorbents.takh used as medicines (cholestyramine resins)
Medicines:
Statins (lovastatin, fluvastatin) inhibit HMG-S-CoA reductase, which reduces the synthesis of cholesterol in the liver by 2 times and accelerates its outflow from HDL to hepatocytes.
Suppression of absorption of cholesterol in the gastrointestinal tract - anion exchange
resins (Cholestyramine, Cholestide, Questran).
Nicotinic acid preparations inhibit the mobilization of fatty acids from
depot and reduce the synthesis of VLDL in the liver, and, consequently, the formation of
LDL in the blood
Fibrates (clofibrate, etc.) increase the activity of lipoprotein lipase,
catabolism of VLDL and chylomicrons, which increases the transition of cholesterol from
them into HDL and its evacuation to the liver.
Preparations of ω-6 and ω-3 fatty acids (Linetol, Essentiale, Omeganol, etc.)
increase the concentration of HDL in plasma, stimulate bile secretion.
Suppression of enterocyte function with the antibiotic neomycin, which
reduces fat absorption.
Surgical removal of the ileum and cessation of bile acid reabsorption.
DISORDERS OF LIPOPROTEIN METABOLISM
Changes in the ratio and number of lipoprotein classes are not always consistent with
are driven by hyperlipidemia, therefore, the identification of dyslipoproteinemia.
The causes of dyslipoproteinemia may be a change in the activity of enzymes
lipoprotein metabolism - LCAT or LPL, reception of LP on cells, impaired synthesis of apoproteins.
There are several types of dyslipoproteinemia.
TypeI: Hyperchylomicronemia.
Caused by genetic deficiency lipoprotein lipase.
Laboratory indicators:
an increase in the number of chylomicrons;
normal or slightly elevated content of preβ-lipoproteins;
a sharp increase in the level of TAG.
CS / TAG ratio< 0,15
Clinically manifested at an early age by xanthomatosis and hepatosplenomega-
Lia as a result of lipid deposition in the skin, liver and spleen. Primary type I hyperlipoproteinemia is rare and manifests at an early age, secondary- accompanies diabetes, lupus erythematosus, nephrosis, hypothyroidism, manifested by obesity.
TypeII: Hyper-β - lipoproteinemia
Lipid biosynthesis
Triacylglycerols are the most compact form of energy storage in the body. Their synthesis is carried out mainly from carbohydrates that enter the body in excess and are not used to replenish glycogen stores.
Lipids can also be formed from the carbon skeleton of amino acids. Promotes the formation of fatty acids, and subsequently triacylglycerols and excess food.
Biosynthesis of fatty acids
In the process of oxidation, fatty acids are converted into acetyl-CoA. Excess dietary intake of carbohydrates is also accompanied by the breakdown of glucose to pyruvate, which is then converted to acetyl-CoA. This last reaction, catalyzed by pyruvate dehydrogenase, is irreversible. Acetyl-CoA is transported from the mitochondrial matrix to the cytosol as part of citrate (Fig. 15).
Mitochondrial matrix Cytosol
Figure 15. Scheme of acetyl-CoA transfer and the formation of reduced NADPH during fatty acid synthesis.
Stereochemically, the entire process of fatty acid synthesis can be represented as follows:
Acetyl-CoA + 7 Malonyl-CoA + 14 NADPH ∙ + 7H +
Palmitic acid (C 16:0) + 7 CO 2 + 14 NADP + 8 NSCoA + 6 H 2 O,
while 7 molecules of malonyl-CoA are formed from acetyl-CoA:
7 Acetyl-CoA + 7 CO 2 + 7 ATP 7 Malonyl-CoA + 7 ADP + 7 H 3 RO 4 + 7 H +
The formation of malonyl-CoA is a very important reaction in fatty acid synthesis. Malonyl-CoA is formed in the reaction of carboxylation of acetyl-CoA with the participation of acetyl-CoA carboxylase containing biotin as a prosthetic group. This enzyme is not part of the multienzyme complex of fatty acid synthase. Acetite carboxylase is a polymer (molecular weight from 4 to 810 6 Da) consisting of protomers with a molecular weight of 230 kDa. It is a multifunctional allosteric protein containing bound biotin, biotin carboxylase, transcarboxylase and an allosteric center, the active form of which is a polymer, and the 230-kDa protomers are inactive. Therefore, the activity of formation of malonyl-CoA is determined by the ratio between these two forms:
Inactive protomers active polymer
Palmitoyl-CoA, the end product of biosynthesis, shifts the ratio towards the inactive form, and citrate, being an allosteric activator, shifts this ratio towards the active polymer.
Figure 16. Mechanism of malonyl-CoA synthesis
In the first step in the carboxylation reaction, bicarbonate is activated and N-carboxybiotin is formed. At the second stage, the nucleophilic attack of N-carboxybiotin by the carbonyl group of acetyl-CoA occurs, and malonyl-CoA is formed in the transcarboxylation reaction (Fig. 16).
Fatty acid synthesis in mammals is associated with a multi-enzyme complex called fatty acid synthase. This complex is represented by two identical multifunctional polypeptides. Each polypeptide has three domains, which are located in a certain sequence (Fig.). First domain responsible for the binding of acetyl-CoA and malonyl-CoA and the connection of these two substances. This domain includes the enzymes acetyltransferase, malonyltransferase, and an acetyl-malonyl-binding enzyme called β-ketoacyl synthase. Second domain, predominantly responsible for the reduction of the intermediate obtained in the first domain and contains acyl transfer protein (ACP), β-ketoacyl reductase and dehydratase and enoyl-ACP reductase. IN third domain the enzyme thioesterase is present, which releases the formed palmitic acid, consisting of 16 carbon atoms.
Rice. 17. Structure of the palmitate synthase complex. Domains are marked with numbers.
Mechanism of fatty acid synthesis
At the first stage of fatty acid synthesis, acetyl-CoA is attached to the serine residue of acetyltransferase (Fig...). In a similar reaction, an intermediate is formed between malonyl-CoA and the serine residue of malonyltransferase. The acetyl group is then transferred from the acetyltransferase to the SH group of the acyl-carrying protein (ACP). At the next stage, the acetyl residue is transferred to the SH-group of the cysteine of -ketoacyl synthase (condensing enzyme). The free SH group of the acyl-carrying protein attacks the malonyl transferase and binds the malonyl residue. Then the condensation of malonyl and acetyl residues occurs with the participation of -ketoacyl synthase with the elimination of the carbonyl group from malonyl. The result of the reaction is the formation of -ketoacyl associated with ACP.
Rice. Reactions for the synthesis of 3-ketoacyl-APB in the palmitate synthase complex
Then, the enzymes of the second domain participate in the reactions of reduction and dehydration of the intermediate -ketoacyl-ACP, which end with the formation of (butyryl-ACB) acyl-ACP.
Acetoacetyl-APB (-ketoacyl-APB)
-ketoacyl-ACP reductase
-hydroxybutyryl-APB
-hydroxyacyl-ACP-dehydratase
Enoyl-ACP-reductase
Butyryl-APB
After 7 reaction cycles
H 2 O palmitoylthioesterase
The butyryl group is then transferred from APB to the cis-SH residue of -ketoacyl synthase. Further elongation by two carbons occurs by attaching malonyl-CoA to the serine residue of malonyltransferase, then the condensation and reduction reactions are repeated. The whole cycle is repeated 7 times and ends with the formation of palmitoyl-APB. In the third domain, palmitoylesterase hydrolyzes the thioether bond to palmitoyl-APB and free palmitic acid is released from the palmitate synthase complex.
Regulation of fatty acid biosynthesis
The control and regulation of fatty acid synthesis is, to a certain extent, similar to the regulation of glycolysis, citrate cycle, and β-oxidation of fatty acids. The main metabolite involved in the regulation of fatty acid biosynthesis is acetyl-CoA, which comes from the mitochondrial matrix as part of citrate. The malonyl-CoA molecule formed from acetyl-CoA inhibits carnitine acyltransferase I and fatty acid β-oxidation becomes impossible. On the other hand, citrate is an allosteric activator of acetyl-CoA carboxylase, and palmitoyl-CoA, steatoryl-CoA, and arachidonyl-CoA are the main inhibitors of this enzyme.
Intermediate products of respiration processes serve as a source of carbon skeletons for the synthesis of lipids - fat-like substances that are part of all living cells and play an important role in life processes. Lipids act both as reserve substances and as components of the membranes surrounding the cytoplasm and all cell organelles.
Membrane lipids differ from ordinary fats in that one of the three fatty acids in their molecule is replaced by phosphorylated serine or choline.
Fats are present in all plant cells, and since fats are insoluble in water, they cannot move around in plants. Therefore, the biosynthesis of fats should occur in all organs and tissues of plants from the dissolved substances entering these organs. Such soluble substances are carbohydrates that enter the seeds from assimilating *. The best object for studying the biosynthesis of fats are the fruits of oil plants, at the beginning of the development of oil seeds, the main components of the seeds are water, proteins, non-protein nitrogenous compounds and insoluble sugars. During maturation, on the one hand, the synthesis of proteins from non-protein nitrogenous compounds occurs, and on the other, the transformation of carbohydrates into fats.
We will focus on the conversion of carbohydrates into fats. Let's start simple. From the composition of fats. Fats are made up of glycerol and fatty acids. Obviously, during the biosynthesis of fats, these components should be formed - glycerol and fatty acids, which are part of the fat. In the biosynthesis of fat, it was found that fatty acids do not combine with bound glycerol, but with its phosphorylated * - glycerol-3phosphate. The starting material for the formation of glycerol-3phosphate is 3-phosphoglyceraldehyde and phosphodioxyacetone, which are intermediate products of photosynthesis and anaerobic decomposition of carbohydrates.
The reduction of phosphodioxyacetone to glycerol-3phosphate is catalyzed by the enzyme glycerol phosphate dehydrogenase, the active group of which is nicotinamide adenine dinucleotide. The synthesis of fatty acids proceeds in more complex ways. We have seen that most vegetable fatty acids have even number carbon atoms C 16 or C 18. This fact has attracted the attention of many researchers for a long time. It has been repeatedly suggested that fatty acids can be formed as a result of the free condensation of acetic acid or acetaldehyde, i.e. from compounds having two carbon atoms C 2 . The works of our time have established that it is not free acetic acid that takes part in the biosynthesis of fatty acids, but acetyl coenzyme A associated with coenzyme A. At present, it is fashionable to depict the scheme for the synthesis of fatty acids as follows. The starting compound for the synthesis of fatty acids is acetyl coenzyme A, which is the main product of the anaerobic breakdown of carbohydrates. Coenzyme A can take part in the synthesis of a wide variety of fatty acids. The first * of these processes is the activation of acids under the action of ATP. At the first stage, acetyl coenzyme A is formed from acetic acid under the action of the enzyme acetyl coenzyme A * and the expenditure of ATP energy, and then * i.e. carboxylation of acetyl coA occurs and the formation of 3-carbon compounds. At the subsequent stages, the molecule of acetyl coenzyme A. ************** condenses
The synthesis of fatty acids occurs by binding a molecule of acetyl coenzyme A. This is the first stage in the actual synthesis of fatty acids.
The general pathway for the formation of fats from carbohydrates can be represented as a diagram:
glycerol-3phosphate
Carbohydrates
Acetyl coenzyme A → fatty acid → fats
As we already know, fats in it can move from one plant tissue to another, and they are synthesized directly in the places of accumulation. The question arises, in what parts of the cell, in what cellular structures are they synthesized? In plant tissues, fat biosynthesis is almost completely localized in mitochondria and spherosomes. The rate of fat synthesis in cells is closely related to the intensity of oxidative processes, which are the main sources of energy. In other words, the biosynthesis of fats is closely related to respiration.
The breakdown of fats most intensively occurs during the germination of seeds of oil plants. Oilseeds contain few carbohydrates and the main reserve substances in them are fats. Fats differ from carbohydrates and proteins not only in that much more energy is released when they are oxidized, but also in that when fats are oxidized, increased amount water. If during the oxidation of 1 g of proteins 0.41 g of water is formed, with the oxidation of 1 g of carbohydrates 0.55 g, then with the oxidation of 1 g of fat 1.07 g of water. It has great importance for the developing embryo, especially when seeds germinate in dry conditions.
In works related to the study of the breakdown of fats, it has been proved that in germinating seeds, along with a decrease in fats, carbohydrates accumulate. How can carbohydrates be synthesized from fats? In general form, this process can be represented as follows. Fats are broken down into glycerol and fatty acids by the action of lipase with the participation of water. Glycerol is phosphorylated, then oxidized and converted to 3-phosphoglyceraldehyde. 3-phosphoglyceraldehyde isomerizes to give phosphodioxyacetone. Further, under the action of * and 3-phosphoglyceraldehyde and phosphodioxyacetone, fructose-1.6 diphosphate is synthesized. fructose-1.6 diphosphate formed, as we already know, turns into a wide variety of carbohydrates that serve to build plant cells and tissues.
What is the path of transformation of fatty acids that are split off under the action of lipase on fats? At the first stage, the fatty acid, as a result of the reaction with coenzyme A and ATP, is activated and acetyl coenzyme A is formed.
R CH 2 CH 2 COOH + HS-CoA + ATP → RCH 2 CH 2 C-S - CoA
The activated fatty acid, acetyl coenzyme A, is more reactive than the free fatty acid. In subsequent reactions, the entire carbon chain of the fatty acid is split into two-carbon fragments of acetyl coenzyme A. The general scheme for the breakdown of fats in a simplified form can be represented as follows.
Conclusion on the synthesis of the breakdown of fats. Both in the breakdown and in the synthesis of fatty acids, the main role belongs to acetyl coenzyme A. Acetyl coenzyme A, formed as a result of the breakdown of fatty acids, can further undergo various transformations. The main way of its transformations is complete oxidation through the cycle of tricarboxylic acids to CO 2 and H 2 O with the release of a large amount of energy. Part of acetyl coenzyme A can be used for the synthesis of carbohydrates. Such transformations of acetylcoenzyme A can occur during the germination of oilseeds, when a significant amount of acetic acid is formed as a result of the amino acid breakdown of fatty acids. During the biosynthesis of carbohydrates from acetyl coenzyme A OH, i.e. acetyl coenzyme A is included in the so-called glyoxylate cycle or the glyoxynic acid cycle. In the glyoxylate cycle, isocitric acid is cleaved into succinic and glyoxic acids. Succinic acid can take part in the reaction of the tricarboxylic acid cycle and, through *, form malic acid and then oxaloacetic acid. Glyoxic acid enters CO compounds with the second molecule of acetyl coenzyme A and as a result of this, malic acid is also formed. In subsequent reactions, malic acid is converted into oxaloacetic acid - phosphoenolpyruvic acid - phosphoglyceric acid and even carbohydrates. Thus, the energy of the acids of the acetate molecule formed during the decay is converted into carbohydrates. What is the biological role of the glyoxylate cycle? In the reactions of this cycle, glyoxylic acid is synthesized, which serves as the starting compound for the formation of the amino acid glycine. The main role due to the existence of the glyoxylate cycle, the acetate molecules formed during the breakdown of fatty acids are converted into carbohydrates. Thus, carbohydrates can be formed not only from glycerol, but also from fatty acids. Synthesis of final photosynthetic products of assimilation, carbohydrates, sucrose and starch in a photosynthetic cell is carried out in uncoupled manner: sucrose is synthesized in the cytoplasm, starch is formed in chloroplasts.
Conclusion. Sugars can enzymatically pass one into another, usually with the participation of ATP. Carbohydrates are converted into fats through a complex chain of biochemical reactions. Carbohydrates can be synthesized from the breakdown products of fats. Carbohydrates can be synthesized from both glycerol and fatty acids.
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