PYRIDOXAL PHOSPHATE

From Big Medical Encyclopedia

PYRIDOXAL PHOSPHATE - piridoksal-5' - phosphate (2-metil-Z-oksi-4-formil-5-piridilmetil-5 '-phosphate), the main biokatalitichesk an active form of vitamin B 6  ; along with other forms of vitamin B 6 , it is used as medicine (see. Piridoksin ).

In live organisms of P. it is formed of a pyridoxine in - result of its oxidation 4' - oxymethyl group in aldehydic under the influence of enzyme of a piridoksinoksidaza (a pyridoxine dehydrogenase; KF 1. 1. 1. 65) and the subsequent phosphorylation 5 '-oxymethyl group with participation of ATP under the influence of a pyridoxal kinase (KF 2. 7. 1. 35).

The item is a part of active centers a glycogen - phosphorylases (KF 2. 4. 1. 1), and also the enzymes catalyzing various transformations of amino acids in live organisms. Aminotransferases are among these enzymes (transaminases; KF 2. 6. 1. 1 — 52), racemase of amino acids (KF 5. 1. 1. 10), decarboxylases of amino acids (KF 4. 1. 1. 12 — 30), kinureninaza (KF 3. 7. 1. 3), tsistationaza (KF 4. 4. 1. 1), serine - and treonindegidra-Tazy (KF 4. 2. 1. 16), tyrosine — a fenolliaza (KF 4. 1. 99. 2), tryptophanase (KF 4. 1. 99. 1), alliinaza (KF 4. 4. 1. 4), tsistationin-, tryptophane - and threoninesynthases (KF 4. 2. 1. 22; 4. 2. 99. 9; 4. 2. 1. 20; 4. 2. 99. 2), serine — gidroksilmetil-transferase (KF 2. 1. 2. 1), etc. P. is also a part of the enzymes participating in synthesis of a carbon skeleton of sphingosine (KF 2. 3. 1. 50) and δ-aminolevulinic to - you to - you to - you (((KF 2. 3.1. 37). The item joins specific proteins apoenzymes at means of aldehydic and phosphatic groups, phenolic hydroxyl and a nitrogen atom of a pyridinic ring. The aldehydic group P. forms al - a dimine or azomethine double bond (Schiff base) with ε-NH 2 - group of the rest of a lysine in a molecule of protein. Other bonds between P. and protein are either ionic, or hydrogen. In phosphorylase catalytic function is carried out with the participation of 5' - phosphatic group P., and in other enzymes — with the participation of 4 '-aldehydic group.

Free P.'s solutions possess characteristic absorption spectrums with a maximum at 293 nanometers in acid medium and at 388 nanometers in neutral and alkaline condition. Molar absorption of solution P. at 388 nanometers in 0,1 N NaOH solution is equal to 6600. Solutions P. and its dry spots on paper intensively fluoresce during the lighting by UV rays. The item easily interacts with carbonyl reagents (e.g., with hydroxylamine, a hydrazine, hydrazides organic to - t, cyanide, bisulphite), and also with NH 2 - groups of primary amines and amino acids. At P.'s interaction with cysteine and others 1, 2 aminothiols form derivative a tlazolidina. The most specific and sensitive method of identification and quantitative definition of P. is the enzymatic method based on activation of akoferment of a tirozindekar-boksilaza (KF 4. 1. 1. 25) from Streptococcus faecalis or a tryptophanase from Escherichia coli.

The general theory of effect of the pyridoxaleft enzymes which substrates are amino acids was developed in 1952 A. E. Braunshteynam and M. M. Shemyakin and in 1954 by D. E. Metzler and Snell (E. E. Snell). According to this theory, catalytic effect of the pyridoxaleft enzymes is caused by ability of aldehydic group of pyridoxal phosphate to form aldimina at interaction with amines, including with amino acids:

In the system of conjugated double bonds arising in the aldimena there is a shift of electrons in the direction from alpha and carbon atom of amino acid to an electron - acceptorly to a nitrogen atom of a piridiniyevy ring. Decrease in electron density at alpha carbon leads to polarization of bonds of this atom. According to H. Dunathan's hypothesis, the greatest labilization and a gap that from bonds at alpha and carbon atom of amino acid which is located in the plane is exposed, perpendicular to the plane of a piridiniyevy ring

of P. V. a case of aminotransferases, racemases and some other piridok-salzavisimy enzymes such communication is communication of alpha and carbon atom with hydrogen atom, in case of decarboxylases — communication of alpha and carbon atom with a carboxyl group. Thus, the nature of reaction is defined by features of geometry of an active center of an apoenzyme. At transamination aldimin P. turns into tautomeric ketimine which is easily hydrolyzed with education pyridoxamine-phosphate and alpha-ketonic acids (see. Aminotransferases ). Aminotransferases differ from all other pyridoxaleft enzymes in the fact that coenzymatical functions in them can be performed as P., and piridoksaminfosfat, exposed to interconversion during enzymatic reaction.

Racemization of alpha amino acids under the influence of racemases is also carried out by formation of an aldimin of P. and its reversible turning into ketimine. This transformation connected with dissociation of hydrogen atom at and - carbon atom and movement of double personalized bond, leads to temporary disappearance of the asymmetric center and to racemization of a molecule. The mechanism of reactions of racemization of amino acids differs from the mechanism of transamination in the fact that the ketimine arising in the course of racemization is not exposed to hydrolysis, and passes into DL альдимин which is hydrolyzed with formation of D,L - amino acids. At decarboxylation and - amino acids unlike transamination and racemization do not occur dissociation of hydrogen at and - carbon atom and formation of ketimine; eliminating of a carboxyl group follows directly education a coenzyme - a substrate aldimin.

Researches of the purified pyridoxaleft enzymes confirmed in the main the representations stated above. These researches, however, showed that at the first stage of effect of the specified enzymes there is not a condensation of free aldehydic group P. to substrate amino acid, and substitution reaction, during which NH 2 - the group of substrate forces out ε-NH 2 - group of a lysine in protein from aldiminny communication with pyridoxal phosphate with education a coenzyme - a substrate aldimin.

It is established also what in many pyridoxaleft enzymes P. performs not only catalytic coenzymatical function, but also participates in maintenance of quarternary oligomerous structure of the fermental protein constructed of several subunits.

At insufficiency of vitamin of Wb there is a falloff of activity of the pyridoxaleft enzymes in fabrics (uneven in different bodies) owing to their transition to a form of apoenzymes, and also reduction of speed of synthesis of some of them, napr, tyrosine-aminotransferase (KF 2. 6. 1. 5) in a liver.

There are data that genetically caused disturbance of biosynthesis ornithine-aminotransferase (KF 2. 6. 1. 13) at the person and the accumulation of ornithine in fabrics connected with it plays a key role in a pathogeny of the hereditary disease leading to a blindness — a circular atrophy of vascular and mesh covers of an eye. Definition of activity aspartate - and alaninaminotranspherases in blood of the person is widely used in diagnosis of some heart diseases and a liver.



Bibliography: Braunstein A. Ts. and Shemyakin M. M. The theory of the processes of amino-acid exchange catalyzed by the pyridoxaleft enzymes, Biochemistry, t. 18, No. 4, page 393, 1953, bibliogr.; Bukin Yu. V. Activity of a pyridoxal kinase and contents piridoksal-R in tissues of mammals is normal also at some experimental influences, in the same place, of t. 41, century 1, page 81, 1976; Bukin Yu. V. and Ivanov And. JI. Distribution and activity of a pyridoxal kinase in a brain of the person in the course of ontogenesis, in the same place, century 2, page 237; Metsler D. Biochemistry, the lane with English, t. 2, page 209, M., 1980; Dunathan - N. S. of Conformation and reaction specificity in pyridoxal phosphate enzymes, Proc. nat. Acad. Sci. (Wash.), v. 55, p. 712, 1966; The enzymes, ed. by P. D. Boyer a. o., v. 2, p. 113, N.Y., 1960, v. 9, p. 379, N. Y. — L., 1973; S h i h V. E. a. o. Ornithine ke-toacid transaminase deficiency in gyrate atrophy of the choroid and retina, Amer. J. hum. Genet., v. 30, p. 174, 1978.


Yu. M. Torchinsky.

Яндекс.Метрика