COLLAGEN (grech, kolla glue + gennao to make) — one of the main fibrous proteins of connecting fabric relating to group of scleroproteids. The most part To. it is found as a part of collagenic fibers. To. is the main structural component of collagenic fiber, the main function to-rogo is connected with formation and maintenance of specific structure of bodies and fabrics in the course of growth and development of an organism. The stabilizing, basic function of collagenic fiber is provided at the expense of its unusual biol, and physical. - chemical properties (metabolic inertness, resistance to effect of various substances etc.) which it gains as a result of the arranged aggregation of molecules K. Patol, changes of exchange and structure To. at the person arise, as a rule, at general diseases of connecting fabric (rheumatism, a scleroderma, etc.). Eventually all changes of biosynthesis or disintegration of collagenic proteins found at this or that pathology lead to disturbance of mechanical characteristics of collagenic fiber and, therefore, basic properties of connecting fabric.
To. and a product of its denaturation — gelatin (see) are of considerable interest in connection with use of this protein to production of vascular prostheses and films for treatment of wounds, and also in connection with use in some industries (food, easy, film and photoproduction).
To. it is extremely eurysynusic in various bodies and tissues of vertebrate and backboneless animals; protozoa and bacteria do not support only him.
On amino-acid structure To. differs from the majority markedly proteins (see). The main features of amino-acid structure To., received from any source, the high content of glycine, low content of sulfur-containing amino acids, lack of tryptophane, availability of oxylysine and oxyproline are. To. is a glycoprotein, the content of carbohydrates in Krom can vary depending on a source of receiving protein. Molecule K. more carbohydrates, than a molecule K, as a rule, support backboneless animals. vertebrata. The most part of carbohydrates in To. vertebrata it is identified as a D-galactose and D-glucose.
To. is the only thing from all known proteins, polypeptide chains (alpha chains) to-rogo almost throughout are constructed of the repeating triplets gli - in which any can hold position X and Y, except glycine, the remains of amino acids. Rod-shaped molecule K., the name of tropocollagen (an elementary base unit of collagenic fiber) which received in early researches, has a pier. the weight (weight) apprx. 300 000, length apprx. 300 nanometers and thickness apprx. 1,5 nanometers. It consists of three polypeptide chains representing the twisted spirals «screwed» as if on one general cylinder. Each a-chain (pier. weight apprx. 100 000) has the helical structure similar to structure poly-L - proline. Spirals contain 3 amino-acid rests on one round with one or two hydrogen bindings on a triplet. On N-and C-trailer sites of alpha chains of a molecule K. there are not spiral areas (bodied peptides), free of regularly repeating amino-acid triplets.
Depending on a chemical structure of the alpha chains which are a part of a collagenic molecule distinguish 4 types K.: The I type supports in the molecule two alfa1 (I) - chains and one alfa2-chain, the II type — three alfa1 (II) - chains, the III type — three alfa1 (III) - chains and the IV type — three alfa1 (IV) chains. Each type of connecting fabric is characterized, in turn, and existence To. certain type: in skin and a bone tissue collagen like I, in cartilaginous tissue — type II, in basal membranes — type IV etc. is found generally. Molecular heterogeneity of collagenic proteins can come to light as well within one type of connecting fabric.
Stabilization of structure of a molecule K. and collagenic fiber it is carried out at the expense of noncovalent and covalent cross bonds. Are among the noncovalent stabilizing bonds electrostatic, hydrophobic and hydrogen. Hydrogen bindings of type — CO... HN — are formed between ketonic oxygen and NH group of a peptide bond between chains, and hydrogen bindings of type — OH.... OC — arise at interaction of ketonic oxygen with OH group of the remains of oxyproline. Stabilization of structure To. cross covalent bonds carry out hl. obr. with the assistance of the aldehydic groups which are formed as a result of enzymatic oxidizing deamination ε-NH 2 - groups of certain remains of a lysine and oxylysine. Aldehydic groups of two next a-chains, interacting among themselves, form cross covalent bonds of aldol type. At interaction of aldehydic group of one alpha chain with ε-NH 2 - cross aldiminny bonds arise group of the remains of a lysine or oxylysine of other alpha chain — Schiff of the basis (see).
At a denaturation To., leading to education gelatin in soft conditions (moderate warming up, effect of urea etc.), only noncovalent bonds are terminated. In this case molecule K. breaks up to separate alpha chains, their dimeasures (beta components) or trimmers (gamma components). Hydrolysis of peptide and other covalent bonds happens only at rigid processing To., applied during the receiving food and industrial drugs gelatin and leading to formation of the products not capable to a renaturation (see. Denaturation ).
Synthesis To. is function of cells of a mesenchymal origin which depending on type of connecting fabric received names of fibroblasts, chondroblasts, osteoblasts etc. In certain conditions of a cell of an ectodermal origin can also synthesize To. As well as the majority of other proteins cosecreted in extracellular space To. it is synthesized in a cell on the polysom connected with membranes of an endoplasmic reticulum, in the form of the predecessor - — procollagen (earlier the term «procollagen» was widely used for designation of the soluble fractions K. extracted from fabric by salt solutions at various pH values).
Alpha Chains of procollagen (about - alpha chains) have a little bigger pier. weight, than alpha chains of collagen (120 000 — 140 000), also contain, in addition to telopeptid, on N-and the S-end the additional polypeptides differing on amino-acid structure from spiral sites of a collagenic molecule markedly. In the course of removal from a cell or in extracellular space again synthesized molecules of procollagen turn in To., at the same time from procollagen the additional N-and S-trailer polypeptides containing disulfide (— S — S —) bonds are enzymatically chipped off. Funkts, value of the polypeptides which are chipped off from procollagen is that they facilitate formation of a spiral by the three in the collagenic molecules Pi at the same time prevent their aggregation in a cell.
Synthesis of functionally full-fledged molecules K., i.e. the molecules capable to aggregation, occurs only in the presence in a cell of the special systems which are carrying out post-translational modification of alpha chains To.: hydroxylation of the prolinovy and lizinovy remains and glycosylation of the oksilizinovy remains. Reaction of a hydroxylation of the prolinovy and lizinovy remains about - alpha chains is catalyzed by various enzymes (spilled - and lysylhydroxylases) connected with membranes of an endoplasmic reticulum, but the same mechanism is the cornerstone of this reaction. Broadcast of a-chains of procollagen happens also during the blocking of reaction of a hydroxylation, but in this case the formed not hydroxylated procollagen (protocollagen, protoprocollagen) does not cosecrete from a cell. After the end of broadcast of a-chains being a part To. the galactose and glucose contact OH group of one of the remains of oxylysine in the form of disaccharide (glucosyl galactose). This process also happens with the participation of the enzymes connected with membranes — collagenic galaktozil-and glyukoziltransferaz.
In disintegration of collagenic proteins in an organism the major role is played by special enzyme — the collagenase splitting a molecule K. on two fragments, components 3/4 and 1/4 from its length. As a result stability of structure goes down To. also its splitting is facilitated by other proteolytic enzymes (acid and neutral proteases of a lysosomic origin) which do not work on native To.
In a light microscope collagenic fibers are found in the form of structures from in parallel the located fibrillar elements possessing double refraction. Average diameter of collagenic fiber can vary depending on type of connecting fabric and it funkts, states. Cross striation is one of characteristic signs of collagenic fiber; this striation is found in electronic and microscopic pictures in the form of the alternating dark and ghost lines (fig). The combination of a dark and light strip makes in fiber one main period, the size to-rogo, equal on average 64 — 70 nanometers, can vary depending on a way of processing and tightness of fiber. Within one main period in collagenic fibers additional dark strips which number depending on a way of preparation of fiber for a submicroscopy fluctuates from 4 to 16 come to light in certain conditions. Cross striation of collagenic fiber is explained by various «packaging» of certain sites of molecules K., what is caused, in turn, by uneven distribution of the amino-acid remains. In those sites where the polar amino-acid remains (arginine, a lysine, asparaginic and glutaminic prevail to - you etc.), «packaging» is less arranged; it corresponds to dark strips. Strictly arranged packaging inherent in ghost lines is caused by concoction in these sites of the non-polar amino-acid remains (proline, hydroxy-amino acids etc.). Specific distribution of the non-polar and polar amino-acid remains during the formation of collagenic fiber is carried out due to side interaction of molecules K. and their shifts concerning each other in the course of aggregation at 0,4 lengths of the main period.
Speed of formation of collagenic in vivo or in vitro fiber to a large extent depends on the size pH, temperature and presence in the environment of these or those, the substances which are accelerating or slowing down this process (ATP, glikozaminoglikana, urea, ascorbic to - that, catecholamines etc.). At the same time depending on conditions not only fibers of usual type with the period of 64 nanometers, but also other fibrillar structures, napr, units with the period of cross striation of 200 — 300 nanometers can be formed (fibrillar or segmented structures with the big periods).
Processes of biosynthesis, disintegration To. and a fibrillogenesis can proceed with various speed depending on type of connecting fabric, and also change at a row fiziol, and patol, conditions of an organism (age, regeneration, an inflammation, collagenic diseases, avitaminosis, hormonal disturbances etc.). As a rule, biosynthesis To. and formation of collagenic fibers considerably amplify at various processes which are followed by growth of connecting fabric (sclerous changes of vessels and bodies, hron, inflammatory changes, healing of wounds and fractures of bones, etc.)*. These processes can sometimes be reversible and to be followed by sharp strengthening of disintegration by K. Primer of it bystry decrease in contents can be To. in a uterus after the end of pregnancy, removal of collagenic structures in process a metamorphosis of some organisms, a resorption of a bone tissue at changes, etc.
See also Skleroproteida .
Patomorfologiya of collagen
At patol, processes in connecting fabric (see) its basic elements — collagenic fibers change. Most often these changes are result of inflammatory reactions at which there are various transformations as unstructured main substance, and To.
At any inflammatory process collagenic fibers bulk up, then there is their fragmentary disintegration and dissolution under the influence of proteolytic enzymes of polymorphonuclear leukocytes and phagocytes. In the course of disintegration collagenic fibers lose tinktorialny properties inherent in them and cease to be painted in gistol. cuts dyes, specific to them, napr, magenta acid.
At collagenic diseases (see) at first there comes hypostasis and swelling of collagenic fibers, and then their fibrinoid treatment (see. Fibrinoid transformation ) and necrosis (see). These changes To. and the subsequent granulematozny reactions make a basis of all patol, the processes proceeding with preferential defeat of connecting fabric: dermatomyositis (see), rheumatism (see), pseudorheumatism (see), acute lupus erythematosus (see), etc.
Patol, manifestations are observed also at insufficient or excess formation of collagenic fibers. E.g., formation of keloid cicatrixes (see. Keloid ) occurs due to excess synthesis To. fibroblasts.
Insufficient kollagenogenez it is characteristic of a row patol, the processes and syndromes described under names desmogenez imperfect (see), bone formation imperfect (see) and chondrogenesis imperfect (see). Here also Marfan's syndrome belongs (see. Marfana syndrome ). Inborn inferiority of a collagenic framework of skin, bones, vessels is characteristic of all these diseases owing to what their mechanical strength sharply decreases.
The reasons hypo - and a giperkollagenogeneza remain not clear. At inborn diseases the speech, obviously, goes about genetic defects. Processes of a kollagenoobrazovaniye at a wound process are more stoutly studied. In particular, it is established that AKTG and glucocorticoids cause early differentiation and maturing of fibroblasts that is followed by disturbance of a kollagenogenez, insufficient formation of granulations and their early maturation with formation of a weak hem. Mineralokortikoidny hormones, somatotropic hormone, thyroxine, thyrocalcitonin, on the contrary, stimulate kollagenogenez so that the rough hem is formed.
Insufficiency of redoxon oppresses proliferation of fibroblasts and suppresses synthesis To. Some researchers believe that at the same time «assembly» of molecules K is broken. owing to oppression of an enzymatic hydroxylation. Gipokollagenogenez is observed also at a radial illness when owing to insufficient differentiation of fibroblasts are formed thin, fragile or, on the contrary, coarse, reinforced collagenic fibers.
Bibliography: Mazurov V. I. Biochemistry of collagenic proteins, M., 1974, bibliogr.; With l at c to both y L. I. Biokhimiya normal and патологически^ the changed connecting fabric, L., 1969, bibliogr.; Biochemistry of collagen, ed. by G. N. Rama-chandran a. A. H. Reddi, N. Y., 1976; B o r n s t e i n P. The biosynthesis of collagen, Ann. Rev. Biochem., v. 43, p. 567,» 1974; G a 1 1 o p P. M. a. P a z M. And. Posttranslational protein modifications, with special attention to collagen and elas-tin, Physiol. Rev., v. 55, p. 418, 1975; Martin G.R., ByersP. H. a. Piez K. A. Procollagen, Advanc. Enzymol., v. 42, p. 167, 1975, bibliogr.
V. I. Mazurov; Residents of Perm (stalemate. An.).