From Big Medical Encyclopedia

PIRIMIDINOVY EXCHANGE — set of synthetic reactions and disintegration of pirimidinovy nucleotides, to-rye along with their purine analogs are used in live organisms for synthesis of nucleic acids. The item of the lake is especially intensively made in the growing fabrics. The inhibition of any stages of P. of the lake can lead to delay and even to dead stop of division and growth of cells. Genetically caused P.'s disturbance by the lake can be the cause of hereditary diseases, napr, orotatsiduriya (see).

Intensive studying of biosynthesis pirimidinovy bases (see) — uracil, thymine and a tsitozin — 20 century when thanks to L. Lagerkvist and P. Reinhard's works, an also of other researchers was established that an intermediate product of biosynthesis of pirimidinovy nucleotides is began in the 50th orotovy acid (see). It was at the same time revealed that a predecessor of one of nitrogen atoms in a pirimidinovy ring is ammonia, and one of carbon atoms joins in a pirimidinovy ring from carbon dioxide. Other carbon atoms of a pirimidinovy ring belong asparaginic to - those.

Fig. 1. Scheme of synthesis of pirimidinovy nucleotides: 1 — reaction is catalyzed aspartate-carba-moiltransferazoy; 2 — reaction of reversible cyclodehydration, is catalyzed by digidroorota-zy; 3 — the reaction of dehydrogenation of dihexahydro-2,6-dioxo-4-pyrimidine carboxylic acid catalyzed by NAD(F) - dependent orotatereductase; 4 — the addition reaction of the 5th '-fos-foribozil-1-pyrophosphate catalyzed orotate-fosforibo-ziltransferazoy; 5 — reaction of decarboxylation orotidin-5 '-monophosphate, catalyzed orotidin-5' - phosphate — a decarboxylase; FFN — a pyrophosphate; UMF — uridine-5 '-monophosphate (uridilovy acid); UDF — uridinediphosphate; UTF — Uri-dintrifosfat; TsTF — tsiti-dintrifosfat.

Biosynthetic reactions of P. of the lake can be divided into the following stages: formation of a pirimidinovy ring in the form of orotovy to - you; transformation orotovy to - you in uridilovy to - that (uridine-5-monophosphate); transformation uridilovy to - you, catalyzed by the corresponding kinases, in the pirimidinovy nucleotides used for synthesis of RNA (ribonucleotides), DNA (deoxyribonucleotides) and some other connections. Mother substances for synthesis of pirimidinovy nucleotides are asparaginic to - that and karbamoilfosfat which is in turn synthesized in an organism from carbon dioxide and ammonia with the participation of ATP (fig. 1).

End products of a chain of biosynthetic reactions of P. of the lake — uridine-triphosphate (UTF) and tsitidintrifos-veils (TsTF) — are used for synthesis of RNA. Synthesis of DNA requires formation of deoxyribonucleotides: dezoksitsitidintrifos-veil (dTsTF) and dezoksitimidintri-phosphate (DTTF). The cytidinediphosphate (TsDF) which is formed under the influence of phosphatase of TsTF turns into dTsDF by direct recovery of a ribozny ring, DTMF turns out by methylation of the pirimidinovy ring entering DUMF.

Fig. 2. Scheme of a catabolism of pirimidinovy nucleotides.

Disintegration of pirimidinovy nucleotides begins with eliminating from them about - phosphorus to - you under the influence of the corresponding nucleotidases. The formed nucleosides are exposed to a phosphorolysis with release of the free pirimidinovy bases and ribozo-or dezoksiribozofosfat. Free tsitozin and 5 methylcytosine at first are deaminized. Catabolic transformations of uracil and thymine consist in recovery of pyrimidines in dihydroderivatives, the ring opening leading to formation of ureido-acids. At the following stages there is a removal of ammonia and carbon dioxide therefore beta alanine or its metilirovanny derivative — beta and aminoisobutyric to - that is formed; beta alanine can be exposed to further disintegration (fig. 2).

It should be noted that synthesis nucleic acids (see) it is regulated not so much at a stage of polymerization of nucleotides how many at a stage of their synthesis. Formation of pirimidinovy nucleotides is regulated on a feedback mechanism. One of end products of a chain of biosynthetic reactions of pirimidinovy exchange — TsTF by direct allosteric impact on the first specific enzyme of synthesis of pirimidinovy nucleotides aspartate-karbamoiltransferazu inhibits synthetic reaction of a karbamoilaspartat. Pirimidinovy nucleotides also inhibit synthesis of three enzymes P. of the lake: aspartate-karbamoiltransferazy, di-gidroorotazy and orotatereductases. One more regulatory enzyme is the kinase catalyzing phosphorylation of timidinovy nucleotides (transformation of DTMF into DTDF and DTTF). Activity of this enzyme is very low in the fabrics consisting of not sharing cells, napr in tissue of a liver, however it sharply increases at once after a partial gepatektomiya. After a partial gepatektomiya also activity aspartate-karbamoiltransferazy increases. In process of recovery of the normal size of body activity of these enzymes is returned to norm. Increase in activity aspartate-karbamoiltransferazy is observed also at Novikov's gepatoma. It should be noted that in all fast-growing fabrics where there is an intensive synthesis nucleinic to - t, are practically absent the enzymes participating in process of disintegration of pirimidinovy nucleotides.

It is necessary to carry malignant anemia to number of diseases at which synthesis of pirimidinovy nucleotides is broken (see. Pernicious anemia ). To lay down. effect of B12 vitamin (see. Cyanocobalamine ) and folic acid (see) at this disease it is connected, apparently with participation of these polyneuramins synthesis of thymine, and also other pyrimidines and purines.

Bibliography: Davidson J. N. Biochemistry of nucleic acids, the lane with English, M., 1976; Crosby Dzh. Biosynthesis, pyrimidinnucleotides, in book; Nucleic acids, under the editorship of E. Chargaff and J. Davidson, lane with English, page 270, M. „1962; Lenindzher A. Biochemistry, the lane with English, M., 1976.

O. D. Lopina.