PRO-INSULIN

From Big Medical Encyclopedia

PRO-INSULIN — biosynthetic predecessor (pro-hormone) insulin, synthesized in beta cells of pancreatic islands — insulae pancreaticae (islets of Langerhans).

Diagrammatic representation of a molecule of pro-insulin: and — the molecule of insulin consisting of two chains; — S-peptide; 1 — dipeptide arginylarginine, 2 — dipeptide an arginyllysine.

In 1969 D. F. Steiner emitted pro-hormone insulin (see) also called it pro-insulin. Studying of the chemical nature of P. showed that it is the polypeptide consisting of 80 — 82 amino-acid remains about a pier. it is powerful (weight) apprx. 10 000. The molecule P. represents a molecule of insulin, the COOH end of the V-chain the cut is connected to NH 2 - the end of the A-chain through dipeptides the arginylarginine and an arginyllysine belonging so-called. To S-peptide (fig).

The number of the amino-acid remains in S-peptides of pro-insulin of animal different types and the person varies from 27 to 32. S-peptides of pro-insulin of a bull, rat, pig and person differ much more, than molecules of the corresponding insulin. So, if insulin of a bull and pig differs from each other only on 3 amino-acid remains, then S-peptides of pro-insulin of the same types — on 11 amino-acid remains. However trailer amino acids of all S-peptides irrespective of a look are identical and are a site of action of proteolytic enzymes therefore the mechanism of transformation of P. into insulin under the influence of proteases is always identical and does not depend on specific differences in molecules P. S-peptide plays an important role in formation of conformation of a molecule P. necessary for formation of a molecule of insulin. Emergence of free S-peptide in blood allows to judge to some extent intensity of transformation of P. into insulin and respectively — a functional condition of the insular device pancreas (see).

The place of synthesis of P. are microsomes of beta cells of pancreatic islands. Assembly of a molecule P. happens in a cytoplasmic reticulum. From ribosomes the molecule of a preproinsulin containing on 14 — 20 amino-acid remains is broadcast it is more, than a molecule P. It is so-called alarm peptide which provides P.'s transfer through a mikrosomny membrane of a ribosomal and membrane complex in intracellular space. There alarm peptide is chipped off, and passes a moleka of la of P. into Golgi's device (a lamellar complex), from to-rogo the secretory granules containing P. and enzymes participating in P.'s transformation into insulin separate (see. Golgi complex ).

P.'s transformation into insulin happens in several stages with participation endo-and ekzopeptidaz (see. Peptide-hydrolase ). As a result of limited proteolysis the intermediate form P. where S-peptide is separated only with NH is formed 2 - the end of the A-chain of insulin, it — intermediat-I, then S-peptide separates from the COOH end of the V-chain of insulin. Under certain conditions S-peptide can separate only in this point, and then in blood appears so-called intermediat-II which represents the molecule of insulin connected to S-peptide through NH 2 - end of the A-chain of insulin. Intermediata I and II possess different biol. activity. The full-fledged molecule of insulin is formed after proteolytic eliminating of S-peptide and connecting dipeptides which can be hydrolyzed to free amino acids — arginine and a lysine. Disturbance of processes of transformation of P. into insulin can lead to change of a ratio between P., its intermediate forms and insulin, to P.'s exit and its intermediate forms in blood and, respectively, to disturbances in a metabolism.

Biol. P.'s activity is studied insufficiently. It is known that P. and its intermediate forms concerning utilization of glucose are less active, than insulin. Low affinity of P. to the receptors which are specifically connecting insulin is noted. It is revealed that P. reacts with antibodies to insulin. S-peptide also has well-marked immune properties that is used at preparation of radio immunological sets for determination of amount of C-peptide in blood serum.

Apply to P.'s definition chromatography (see) on DE-cellulose and more informative — an enzymatic method with use of insulinspetsifichesky protease. This enzyme splits a molecule of insulin in a definite time, but does not work during the same time for a molecule P. then P. can be determined by radio immunological methods.

At a row patol. states secretion of II. and quantity it in blood can change in comparison with norm (5 — 10% of content in blood of insulin). The wedge, a picture in these cases depends on what intermediate form P. came to blood. Secretion of intermediate forms P. can bring to hypoglycemia (see) since intermediata of I and II possess certain insulinopodobny biol, activity. At secretion in blood of not turned P. the content of glucose in blood can increase considerably (see. Hyperglycemia ).

P.'s maintenance in blood is increased at some types insulomas (see), at patients with a diabetes mellitus (see. diabetes mellitus ) at certain stages of a disease, at pancreatitis (see. Pancreatitis ) when inflammatory process takes also endocrine tissue of a pancreas.

As medicine P. do not apply.


Bibliography: Biochemistry of hormones and hormonal regulation, under the editorship of N. A. Yudaye-va, page 93, M., 1976; Cuatrecasas P. Membrane receptors and hormone action, Advanc. Protein Chem., v. 30, p. 251, 1976; Staroseltzeva L. K. 'Enzymic transformation of proinsulin, Ergebn. exp. Med., v. 28, p. 63, 1978; Steiner D. F. Proinsulin and the biosynthesis of insulin, New Engl. J. Med., v. 280, p. 1106, 1969.

L. K. Staroseltseva.

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