Sphingomyelin biological role. Sfingomyelina

Ceramids - a simple type of sphingolipid consisting of sefingosin (or some of its derivatives) and fatty acid (are an important lipid component of the cell membrane)

Formula Sphinomyelin:
Sfigomyelin - This type of sphingolipid, which is located in the cell membrane of animals. Especially this phospholipid is rich in myelin shell of axons of nerve cells.
Sfigomylin is a single human phospholipid, the basis of which does not include the glycerin residue. Sphinomylin consists of Sphingosin, connected by the ester association with the polar group. The polar group may be phosphocholine or phosphoethanolamine. For the second carbon of Sfingosin due to the amide binding, fatty acid is annexed.

2.Acetone formation reaction.
Acetone - organichaving the formula CH 3 -C (O) -CH 3, the simplest representative of saturated ketones.
Acetone, which is formed with non-enzyme decarboxylation of acetoacetate, is not used in the body. It is excreted with the exhaled air, the secret of sweat glands and urine. Normally, the concentration of acetone in the blood is small and ordinary reactions is not determined.

Ketone bodies are synthesized in the liver, easily pass through mitochondrial and cell membranes And enter blood. Blood they are transported to all other fabrics. Only acetoacetate and beta hydroxybutyrate are used.

3. Give overall characteristic The buildings of the acylsintytase and its active centers.
The reactions of the synthesis of fatty acids with the participation of this enzyme.

In the biosynthesis of saturated fatty acids, two enzyme complexes are involved: Acetyl-CoA carboxylase and acylsintytase.
LCD synthetase contains 7 active centers.

The acylsintytase multimestrian complex contains acilperine protein (APB) as a kind of kernel, the active center is presented phosphopransnetic. Other enzymes of the complex are β-ketoacylsintyase (COP) - the largest domain of acylsitetease (N-terminal), its enzyme activity provides the only irreversible reaction of the entire process, acyltransferase (at) - tolerates the acid residue with acyl-koa on the HS group group of the APB domain, β-ketoacylorideuctase (cr), IN- hydroxycyl dehydratesis (GD), eNOILEDUCTAZ (EP) and acyltransacetylase (at).

After that, the acyl-APB enters a new synthesis cycle. A new molecule of Malonil-Koah is joined to the free SH group of acilperine protein. Then the excite residue is cleaned, and it is transferred to a small residue with simultaneous decarboxylation, and the reaction cycle is repeated.

Thus, the hydrocarbon chain of future fatty acid is gradually growing (for each cycle - by two carbon atoms). This occurs until it extends to 16 carbon atoms (in the case of palmitic acid synthesis) or more (synthesis of other fatty acids). After this, Tioliz occurs, and the active form of fatty acid is formed in the finished form - Acyl-CoA.

Sphingolipid. These are mainly in the membranes of animals and vegetable cells. Nervous fabric is especially rich. Sphingomyelina also found in kidney fabrics, liver and other organs. In the hydrolysis of the spongomyelin, they form one fatty acid molecule, one molecule of ductomic unsaturated spingosin alcohol, one molecule of a nitrogen base (more often it is choline) and one phosphoric acid molecule. The general formula of sphingomyelin can be represented as:

The general plan for constructing a sphingomyeline molecule in a certain respect resembles the structure of glyceluphospolipids. The Sphin-Homelin molecule contains a polar "head", which is also a positive (the residue of choline), and the negative (the residue of phosphoric acid) charges, and two non-polar "tail" (long aliphatic sfingosin chain and an acyl radical of fatty acid). In some sphingomyelines, such as selected from the brain and spleen, instead of Sfingosin found alcohol dihydrosfingosine (restored Sphingosin):

7.6 steroids

All considered lipids are customary to be mischievable, since soaps are formed when they are alkaline hydrolysis. However, there are lipids that are not hydrolyzed with the liberation of fatty acids. These lipids include steroids. Steroids are widespread connections in nature. They are often found in the association with fats. They can be separated from fat by waters (they fall into a unlimited fraction). All steroids in their structure have a kernel formed by hydrogenated phenanthrene (rings A, B and C) and cyclopentane (ring D) (Fig. 24):

Figure 24 - generalized steroid kernel
Steroids include, for example, hormones of adrenal cortical substances, bile acids, vitamins of groups D, heart glycosides and other connections. In the human body, sterols occupy an important place among steroids (sterols), i.e. Steroid alcohols. The main representative of Sterin is cholesterol (cholesterol).

Due to the complex structure and asymmetry of the steroid molecules have many potential stereoisomers. Each of the hexagon rings (rings A, B and C) of the steroid nucleus can take two different spatial conformations - the conformation of the "chair" or "boats".

Cholesterol is a source of formation in the organism of mammalian bile acids, as well as steroid hormones (sex and corticoid). Cholesterol, or rather, the product of its oxidation is 7-dehydroholesterol, under the action of UV rays in the skin turns into vitamin D 3. Thus, the physiological function of cholesterol is diverse.

Cholesterol is in animals, but not in plant fats. In plants and yeast, the compounds are close in structure to cholesterol, including ergosterner.

Ergosterian is the predecessor of vitamin D. After exposure to Ergosterian UV rays, it acquires a property to have an anticipated effect (when the ring in the rings).

Double bond reduction in cholesterol molecule leads to the formation of a coprotine (copostant bar). The coprogen is in the composition of the feces and is formed as a result of the reduction of the intestinal microflora in cholesterol between atoms from 5 and c 6.

These sterols, unlike cholesterol, are very poorly absorbed in the intestines and therefore are found in human tissues in trace quantities.

8 Chemistry of carbohydrates

For the first time, the term "carbohydrates" was proposed by Professor Derptsky (now Tartu) University K.G. Schmidt in 1844 at that time assumed that all carbohydrates have a general formula C m (H 2 O) N, i.e. Carbohydrate + water. Hence the name "Carbohydrates". For example, glucose and fructose have a formula C (H 2 O) 6, cane sugar (sucrose) C 12 (H 2 O) 11, starch [C 6 (H 2 O) 5] N, etc. In the future, it turned out that a number of compounds in their properties relating to the class of carbohydrates contain hydrogen and oxygen in a slightly different proportion than indicated in the general formula (for example, deoxyribosis with 5 H 10 o 4). In 1927, the International Commission on Reform chemical nomenclature He proposed the term "carbohydrates" to replace the term "glycides", but the old name "carbohydrates" was rooted and is generally accepted.

Chemistry of carbohydrates occupies one of the leading places in the history of development. organic chemistry. Cane sugar can be considered first organic compoundallocated in a chemically pure form. Produced in 1861 A.M. Butleric synthesis (outside the body) of carbohydrates from formaldehyde was the first synthesis of representatives of one of the three basic classes of substances (proteins, lipids, carbohydrates), which are part of living organisms. The chemical structure of the simplest carbohydrates was found out in late XIX. in. As a result of fundamental research by E. Fisher. A significant contribution to the study of carbohydrates was made by domestic scientists A.A. Collie, p.p. Shoreigin, N.K. Kochetkov et al. In the 20s of the present century, the works of the English researcher, W. Heuorz, the foundations of the structural chemistry of polysaccharides were laid. From the second half of the XX century. There is a rapid development of chemistry and biochemistry of carbohydrates, due to their important biological meaning.

Sfingomyelina - Sophisticated lipids, which include aminoospyrt sefingosin or its polyunsaturated analogs, choline, the residue of phosphoric acid and the residue of fatty acid. The genetically determined violation of S. exchange is based on severe enzymopathy (see).

S. were opened in 1884 by Tudi-Hum (L. J. W. Thudichum) and allocated in 1901, they are widespread in nature, part of the membranes of animals and vegetable cells. Especially rich in S. Nervous fabric. OK. 20% of all phospholipids of the brain (see phosphatides) are accounted for by S. in myeline, white and gray matter of the human brain C. are 7-8% of the total lipid (see). In phospholipids, the erythrocyte membranes discovered 15-16% C., and 80-85% of these C. are in the outer layer of membranes. In the blood plasma, the concentration of C. is equal to 10-50 mg / 100 ml (according to other data, 10-30 mg / 100 ml), which is an average of 18-20% of the total amount of blood plasma phospholipids. C. Particularly included in lipoproteins (see) blood plasma.

N. V. Glyaeva.

Sfingomyelin

The first part of the word "Sfingo" suggests that the molecule includes instead of glycerin ductomic unsaturated alcohol - Sfingosin. The most widespread representatives of this group of compounds are the spingomylin of Sphingomylin detected in the membranes of plant and animal cells; Nervous fabric is especially rich in spingofospholipids, and in particular, the brain.

The characteristic feature of phospholipids is their dilution, that is, the ability to dissolve both in the aqueous medium and in neutral lipids. This is due to the presence of pronounced polar properties in phospholipids. At pH 7.0, their phosphate group always carries a negative charge. Nitrogen-containing groupings in phosphatidylcholine (choline) and phosphatidyl ethanolmine (ethanolamine) at pH 7.0 carry a positive charge. Thus, at pH 7.0, these glyceorophospolipids are bipolar zwitterions and their total charge is zero. The residue of the serine in the phosphatidylserine molecule contains an  amino group and a carboxyl group. Consequently, at pH 7.0, phosphatidylserine molecule has two negative and one positively charged groups and carries a total negative charge.

At the same time, fatty acid radicals in phospholipids do not have an electric charge in an aqueous medium and thus determine the hydrophobicity of the part of the phospholipid molecule. The presence of polarity due to the charge of polar groups determine hydrophilicity. Therefore, on the surface of the section, oil-water phospholipids are arranged in such a way that the polar groups are in the aqueous phase, and non-polar groups in oil. Due to this, in the aqueous medium, they form a bimolecular layer, and when a certain critical concentration is reached, micelles.]

This is based on phospholipid participation in building biological membranes.

The processing of the aqueous medium of a difid lipid ultrasound leads to the formation of liposomes. The liposome is a closed lipid bilayer, inside which is part of the aquatic environment. Liposomes are used in the clinic, cosmetology as peculiar containers and carriers of drugs, nutrients to certain organs and for combined action on the skin.

The functional role of phospholipids is not limited to their participation in the construction of biomembranes. So, they are regulators of enzyme activity. For example, phosphatidylcholine, phosphatidylserin, sphingomylin activate or inhibit the activity of enzymes catalyzing blood coagulation processes. The lipid regulatory function lies in the fact that a number of hormones (sex, adrenal cortex hormones) are lipid derivatives. In addition, phospholipids

Perform detergent function in the intestines and a gallbladder. They are an important structural component of bile, along with free cholesterol and with bile acids. Changing the relationship of any of these components leads to precipitation and formation of bile stones. Phospholipids are also an important component of mixed micelles that are formed during the digestion of lipids.

It is a source of arachidonic acid - eikosanoid precursor

Are sources of secondary messengers - diacylglycerol and inositatrimphate, which has already been mentioned above

Provide protein attachment to the membrane. Some extracellular proteins are attached to the outer side of the plasma membrane due to the formation of covalent bonds with phosphatidylositol. An example of such proteins can be enzymes: alkaline phosphatase, lipoprotein of lipase, cholinesterase.

Take part in the formation of transport forms of other lipids

Can perform energy function

Are encountered component of the lung surfactant (see below)

Federal Health and Social Development Agency

State Educational Decision of Higher Professional Education Russian State Medical University of the Federal Agency for Health and Social Development

sphingolipid.

Their biosynthesis and biological role

Nikitin Paul 112 Group

Sphingolipids are called a group of complex lipids, the basis of the molecule of which are aliphatic amino alcohols, of which the most common sefingosin and cerebrine.

CH3 (CH2) 12 CH CH CH CH2OH CH3; (CH2) 12 CH2 CH CH CH2OH

OH NH2 OH OH NH2

sphinosin Cerebrin (phytosfingosine)

Sphingolipids divide on 2 main groups:

Sphinophospholipids containing phosphoric acid and choline residues (sphingomyelins) or phosphoric acid and inosylglyglipida (phytosphingolipids);

sphingoglipids containing monosaccharides (usually galactose), or oligosaccharides (cerebroids) ; and residues of sialic acids (gangliosides) .

Sphingomyelins are the most common sphingolipids. They are mainly in the membranes of animals and vegetable cells. Nervous fabric is especially rich; Sphingomyelina also found in kidney tissues, liver and other organs. In the hydrolysis of spongomyelins, one molecule of fatty acid is formed, one molecule of stroke acid, one molecule of ductomic unsaturated aminopirt of Sfingosin, one molecule of a nitrogen base (more often it is choline) and one phosphoric acid molecule, which is why sphingomyelin belongs to the phospholipid class. The overall structure of Sphingomyelinov looks like this:

The conformation of the Sphingomyelin molecule in a certain attitude is similar to the conformation of glyceluphospholipids. Sphinomyelin molecule contains a polar "head", which is also positive (the residue of choline), and the negative (the residue of phosphoric acid) charge, and two non-polar "tail" (long aliphatic sfingosin chain and esterified fatty acid). It should be noted that in some sphingomines, such as selected from the brain and spleen, instead of Sfingosin found alcohol dihydrosfingosine (restored Sphingosin).

Glycolipids are complex lipids containing carbohydrate group molecules (more often than D-galactose residue). Glycolipids play a significant role in the functioning of biological membranes. They are mainly in brain tissue, but also also in blood cells and other tissues. There are three main groups of glycolipids: cerebroids, sulfatis and gangliosides.

Cerebroids do not contain nor phosphoric acid, nor Holin. Their composition includes hexosis (usually D-galactose), which is associated with an essential bond with a hydroxyl group of aminopirt of Sphingosin. In addition, bold acid is included in the cerebralosis. Among these fatty acids, lignocerin, nervous and cerebral acid are most often found, i.e. fatty acids having 24 carbon atoms. The structure of cerebrumoids can be represented by the following scheme;

The most studied representatives of cerebrzyoids are nervous, containing nervous acid, cerebron, which includes cerebral acid, and kerazine containing glygnocyrin acid. Especially great the content of cerebrumonds in the membranes of nerve cells (in myelin shell).

Gangliosides with hydrolysis of ganglioside can be detected by the highest fatty acid, alcohol Sphinosin, D-glucose and D-galactose, as well as derivatives of amino-mahors: N-acetylglucosamine and N-acetyl-neuramic acid. The latter is synthesized in glucosamine organism and has the following formula:

In structurally, gangliosides are largely similar to cerebroids, with the only difference, which instead of one galactose residue they contain complex oligosaccharide. One of the simplest gangliosides is hemathoside isolated from the stroma of red blood cells:

Unlike cerebronides and sulfatides, gangliosides are mainly in the gray matter of the brain and are concentrated in plasma membranes of nerve and glial cells.

All lipids considered above are called washer, since with their hydrolysis, soaps are formed.

Biosynthesis sphingolipid

Sphingolipids can be synthesized from other connections. For their synthesis, the sefingosin is needed primarily, which is formed during several consecutive reactions from Palmitytel-CoA and serine; Activated fatty acids are needed in the form of acyl-co-derivatives; We also need
or Activated choline in the form of a CDF-choline for the synthesis of sphingomyelinov, or activated monomers of carbohydrate nature in the form of their UDF derivatives for the synthesis of cerebrumoids or gangliosides.

Biological role

I. Participation in the work of the immune system

a) the metabolism of sphingolipids in the cells of the immune system and the formation of secondary lipid messengers - ceramide, sefingosin, sefingosine-1-phosphate and ceramide-1-phosphate - are part of a single signaling system controlling maturation, differentiation, activation and proliferation of lymphocytes in response to antigens and Mitogens and programmed cell death after effector function.

b) sphingomylinic cycle products, as well as inhibitor of ceramidxintase - Fumeonizin B1 - affect the expression of surface antigens T lymphocytes - CD3, CD4, CD8, CD25, CD45, change the balance between lymphocyte subpopulations, inhibit DNA synthesis in normal thymus and spleen cells and proliferative response Mitogens and suppress the development of an immune response to T-dependent antigens in vivo.

The early phases of the primary immune response are characterized by proliferation of specific precursors in a special microenvironment of lymphoid tissue, differentiation into effector lymphocytes and migration from lymphoid organs into blood and tissue. The migration of lymphocytes, in particular, depends on the distribution of the antigen in non-lifoid organs and local activation of lymphocytes by molecules of mono nuclear systems.

c) affects the expression of adhesion molecules and MNS, as well as the factors of migration of cells, sphingolipids regulate the directional movement of activated lymphocytes in the tissue. The interaction of all types of effector cells leads to the removal of alien antigen from the body. The action of sphingolipids is implemented at the level of targets common to TCR / CD3-complex and sphingomyelin cycle signaling pathways. Sphingolipids are the most important and indispensable part of the immune system, and as a result, an important part of the whole organism.

II- Participation in the structure and functioning of cell membranes.

Sphingolipids are available in the membranes of animals and vegetable cells; They are the main component of the myelin shell of the meal nerve and lipids of the brain. In fatty sediments almost not contained.

Application in medicine

Sphingolipids are used to treat oncological diseases. Many types of tumor cells and neoplasms can be destroyed by impacts leading to an increase in ceramic sphingolipid concentration. There are many ways to increase the amount of ceramide sfingolipid in the tumor, but their use is complicated by the fact that the ceramide's sfingolipid performs a central role in cell homeostasis: it is easily metabolized to form other sphingolipids that contribute to the growth of the tumor, metastasis and combat the patient's immune system. The need to prevent such metabolic conversion against the background of the simultaneous activation of the enzymes involved in the synthesis of ceramic sfingolipid, enzymes are described, which should be activated or inhibit, as well as drugs, metabolites and components of the ration modifying each enzyme. The importance of the allyl alcohol group in the ceramic sofingolipid molecule and a number of antitumor agents is indicated that the hydroxyl group is involved in the transfer of phosphate from protein to protein by forming phosphate ether. Allyl hydroxyl group may also reduce the number of ketones in mitochondrial ubiquins to form oxygen reactive forms. The level of ceramide sfingolipid in tumors can be increased due to the direct introduction of ceramide's sfingolipid or its analogues; Stimulation of the formation of ceramide sfingolipid from its predecessors; by hydrolysis of sphingomyelin or glycosphingolipid hydrolysis; Sphingosin acylation. In addition, a higher concentration of ceramide sfingolipid may be due to the slowdown in its conversion in Sfigomylin.