• Domestic science and medicine in the 19th - early 20th centuries Chemistry of the 19th century in medicine
• What are peptides? Types and types of peptides. All about peptides and anti-aging cosmetics with peptides Additional peptides are not formed
• Toxic effect on humans of hazardous chemicals
• Radioautography Method of autoradiography in cytology
• Identification of bacteria by antigenic structure
• Organic matter in wastewater What are organic compounds in water
• Hydrogen index (pH factor)
• What is the pH of water and why is it important to know it?
• Redox potential Redox systems
• Reversible redox system Reversible redox systems

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 fatty acids 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 involved

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. Synthesis of them under pressure, oxidizers, heavy metals. At the same time and during normal life, they are also synthesized.

Hydrophobic regions of proteins come out during heat treatment (are exposed to the outside), these regions 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

five) ? 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 area of ​​primary chromosome constrictions.

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 there are various inclusions (for example, 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.

It's time for nucleoparin proteins. 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.

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 a complex with carnitine, similar to how higher fatty acids are transported inside the mitochondria, but here the transport goes in a different direction, usually as part of citric acid, which is 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 enters the mitochondria (malate-aspartate shuttle) or is decarboxylated to pyruvate by the malic 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. Its chemical structure, biosynthesis and biological role. The reasons

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.

LIPIDS.BIOL.ROLE.CLASSIFICATION.

Lipids are a large group of substances of biological origin, highly soluble in organic solvents such as methanol, acetone, chloroform and benzene. Lipids are the most important source of energy of all nutrients. A number of lipids take part in the formation of cell membranes. Some lipids perform special functions in the body. Steroids, eicosanoids, and some phospholipid metabolites perform signaling functions. They serve as hormones, mediators, and secondary carriers. Lipids are divided into saponifiable and unsaponifiable. Saponifiable lipids.

Saponifiable lipids include three groups of substances: esters, phospholipids and glycolipids. The ester group includes neutral fats, waxes and sterol esters. The phospholipid group includes phosphatidic acids, phosphatides and sphingolipids. The glycolipid group includes cerebrosides and gangliosides).

The group of unsaponifiable lipids includes saturated hydrocarbons and carotenoids, as well as alcohols. First of all, these are alcohols with a long aliphatic chain, cyclic sterols (cholesterol) and steroids (estradiol, testosterone, etc.). Fatty acids form the most important group of lipids. This group also includes eicosanoids, which can be considered as derivatives of fatty acids.

Lipid digestion and absorption of lipid digestion products.

In the oral cavity, fats do not undergo any changes, because. saliva does not contain enzymes that break down fats. Although there is no noticeable digestion of food fats in the stomach of an adult, partial destruction of lipoprotein complexes of food cell membranes is still noted in the stomach, which makes fats more accessible for subsequent exposure to pancreatic juice lipase. The breakdown of fats that make up food occurs in humans and mammals mainly in the upper sections of the small intestine, where there are very favorable conditions for emulsifying fats. After the chyme enters the duodenum, here, first of all, the hydrochloric acid of the gastric juice is neutralized. Fatty acids with a short carbon chain and glycerol, being highly soluble in water, are freely absorbed in the intestine and enter the blood of the portal vein, from there to the liver, bypassing any transformations in the intestinal wall. Fatty acids with long carb. the chain is more difficult to absorb. With the help of bile, bile salts, phospholipids and cholesterol image. Micelles that are freely absorbed in the intestine.

3. Hydrolysis of triacylglycerides. Resynthesis of fats. Triacylglycerides are the most abundant lipids in nature. They are usually divided into fats and oils. Hydrolysis of triacylglycerols produces glycerol and fatty acids. Complete hydrolysis of triglycerides occurs in stages: first, bonds 1 and 3 are rapidly hydrolyzed, and then the hydrolysis of 2-monoglyceride slowly proceeds .. (hydrolysis). Resynthesis of fats in the intestinal wall. In the intestinal wall, fats are synthesized that are largely specific to this type of animal and differ in nature from dietary fat. The mechanism of resynthesis of triglycerides in the cells of the intestinal wall in general terms is as follows: initially, their active form, acyl-CoA, is formed from fatty acids, after which monoglycerides are acylated to form first diglycerides, and then triglycerides:

4. Bile acids. structure, biol. role. Bile acids are formed from cholesterol in the liver. These 24-carbon steroid compounds are cholanic acid derivatives having one to three α-hydroxyl groups and a 5-carbon side chain with a carboxyl group at the end of the chain. Cholic acid is the most important in the human body. Bile acids ensure the solubility of cholesterol in bile and aid in the digestion of lipids.

Biosynthesis of lipids and their components.

The lipids themselves and some of their structural components enter the human body mainly with food. With insufficient intake of lipids from the outside, the body is able to partially eliminate the deficiency of lipid components through their biosynthesis. So, some saturated acids can be synthesized in the body by enzymatic means. The diagram below reflects the summary of the process of formation of palmitic acid from acetic acid:

CH3COOH + 7HOOC - CH2 - COOH + 28[H]

C15H31COOH + 7CO2 + 14H2O

This process is carried out with the help of coenzyme A, which converts acids into thioethers and activates their participation in nucleophilic substitution reactions:

Some unsaturated acids (for example, oleic and palmitoleic) can be synthesized in the human body by dehydrogenation of saturated acids. Linoleic and linolenic acids are not synthesized in the human body and come only from the outside. The main source of these acids is plant foods. Linoleic acid serves as a source for the biosynthesis of arachidonic acid. It is one of the most important acids that make up phospholipids. Triacylglycerols and phosphatidic acids are synthesized on the basis of glycero-3-phosphate, which is formed from glycerol by its transesterification with ATP. Of the total amount of cholesterol contained in the body, only 20% of it comes from food. The main amount of cholesterol is synthesized in the body with the participation of the coenzyme acetyl-CoA.

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 810 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. AT 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.

After the splitting of polymeric lipid molecules, the resulting monomers are absorbed in the upper part of the small intestine in the initial 100 cm. Normally, 98% of dietary lipids are absorbed.

1. short fatty acids(no more than 10 carbon atoms) are absorbed and pass into the blood without any special mechanisms. This process is important for infants, because. milk contains mainly short- and medium-chain fatty acids. Glycerol is also absorbed directly.

2. Other digestion products (long-chain fatty acids, cholesterol, monoacylglycerols) form with bile acids micelles with a hydrophilic surface and a hydrophobic core. Their size is 100 times smaller than the smallest emulsified fat droplets. Through the aqueous phase, the micelles migrate to the brush border of the mucosa. Here micelles break down and lipid components diffuse inside the cell, after which they are transported to the endoplasmic reticulum.

Bile acids here they can also enter enterocytes and then go into the blood of the portal vein, however, most of them remain in the chyme and reach iliac intestines, where it is absorbed by active transport.

Resynthesis of lipids in enterocytes

Lipid resynthesis is the synthesis of lipids in the intestinal wall from exogenous fats entering here; endogenous fatty acids, so resynthesized fats differ from food fats and are closer in composition to "their" fats. The main objective of this process is to tie dietary medium and long chain fatty acid with alcohol - glycerol or cholesterol. This, firstly, eliminates their detergent effect on membranes and, secondly, creates their transport forms for transfer through the blood into tissues.

The fatty acid entering the enterocyte (as well as any other cell) is necessarily activated through the addition of coenzyme A. The resulting acyl-SCoA is involved in the synthesis of cholesterol esters, triacylglycerols and phospholipids.

fatty acid activation reaction

Resynthesis of cholesterol esters

Cholesterol is esterified using acyl-SCoA and the enzyme acyl-SCoA:cholesterol acyltransferase(AHAT).

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.

Cholesterol ester resynthesis reaction

Resynthesis of triacylglycerols

There are two ways for TAG resynthesis:

The first way, the main - 2-monoacylglyceride- occurs with the participation of exogenous 2-MAG and FA in the smooth endoplasmic reticulum of enterocytes: the multienzyme complex of triacylglycerol synthase forms TAG.

Monoacylglyceride pathway of TAG formation

Since 1/4 of the TAG in the intestine is completely hydrolyzed, and glycerol does not linger in enterocytes and quickly passes into the blood, a relative excess of fatty acids arises for which there is not enough glycerol. Therefore, there is a second glycerol phosphate, a pathway in the rough endoplasmic reticulum. The source of glycerol-3-phosphate is the oxidation of glucose. Here are the following reactions:

1. Formation of glycerol-3-phosphate from glucose.
2. Conversion of glycerol-3-phosphate to phosphatidic acid.
3. The conversion of phosphatidic acid to 1,2-DAG.
4. Synthesis of TAG.

Glycerol phosphate pathway for TAG formation

Resynthesis of phospholipids

Phospholipids are synthesized in the same way as in other cells of the body (see "Synthesis of phospholipids"). There are two ways to do this:

The first route is using 1,2-DAG and active forms of choline and ethanolamine for the synthesis of phosphatidylcholine or phosphatidylethanolamine.

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