Pyridoxine Amino acid decarboxylation

A water-soluble vitamin of the B group. As pyridoxal phosphate, it is a cofactor for amino acid decarboxylation and transamination reactions. A deficiency produces symptoms of skin roughening. The pyridoxine status of the body can be determined by the tryptophan loading test (qv). 

Be Pyridoxine, pyridoxal, pyridoxamine Coenzyme in transamination and decarboxylation of amino acids and glycogen phosphorylase role in steroid hormone action Disorders of amino acid metabolism, convulsions... 

Vitamin Ba (pyridoxine, pyridoxal, pyridoxamine) like nicotinic acid is a pyridine derivative. Its phosphorylated form is the coenzyme in enzymes that decarboxylate amino acids, e.g., tyrosine, arginine, glycine, glutamic acid, and dihydroxyphenylalanine. Vitamin B participates as coenzyme in various transaminations. It also functions in the conversion of tryptophan to nicotinic acid and amide. It is generally concerned with protein metabolism, e.g., the vitamin B8 requirement is increased in rats during increased protein intake. Vitamin B6 is also involved in the formation of unsaturated fatty acids. 

Thiamine, biotin and pyridoxine (vitamin B) coenzymes are grouped together because they catalyze similar phenomena, i.e., the removal of a carboxyl group, COOH, from a metabolite. However, each requires different specific circumstances. Thiamine coenzyme decarboxylates only alpha-keto acids, is frequently accompanied by dehydrogenation, and is mainly associated with carbohydrate metabolism. Biotin enzymes do not require the alpha-keto configuration, are readily reversible, and are concerned primarily with lipid metabolism. Pyridoxine coenzymes perform nonoxidative decarboxylation and are closely allied with amino acid metabolism. 

Transamination reactions require the coenzyme pyridoxal-5 -phosphate (PLP), which is derived from pyridoxine (vitamin B6). PLP is also required in numerous other reactions of amino acids. Examples include racemizations, decarboxylations, and several side chain modifications. (Racemizations are reactions in which mixtures of l- and D-amino acids are formed.) The structures of the vitamin and its coenzyme form are illustrated in Figure 14.2. 

Pyridoxal phosphate is derived from pyridoxine (vitamin Bg). Pyridoxal phosphate is the cofactor not only for transamination reactions but also for decarboxylations and a number of other reactions involving amino acids. 

The vitamin Be group of coenzymes consists of pyridoxine, pyridoxal, and pyridoxamine and their metabolically active phosphorylated forms. They are striking for the variety of enzymic reactions in which they are important, and many amino acid transformations, including various transaminations and decarboxylations, are vitamin B dependent. Compounds with vitamin B activity are apparently not stored in the body in large amounts, and biochemical evidence of B deficiency can develop quickly if intake is inadequate (S4). 

Vitamin is pyridoxal (ll.lOSf), pyridoxine (ll.lOSg) or pyridoxamine (ll.lOSh), all of which exist as their phosphate esters. This vitamin was first isolated in 1936. Pyridoxyl phosphate (ll.lOSi) is a versatile coenzyme used by all living organisms which participates in transamination (11.111) and (11.112), decarboxylation (11.113) and racemisation (11.114) reactions. It is the essential cofactor in amino acid metabolism. Virtually all enzymes which catalyse reactions of 2-amino acids utilise pyridoxyl phosphate as the coenzyme (11.111) through (11.114). 

Most of the vitamin Be in natural materials is present as phosphorylated derivatives of compounds I-III. Pyridoxal-5-phosphate (IV, Fig. i) was discovered in 1944 by Gale and Epps as an unidentified compound required for enzymatic decarboxylation of amino acids Gunsalus and co-workers subsequently showed it to be a phosphorylated pyridoxal -. Pyridoxamine-5-phosphate (V, Fig. i) was discovered by Rabinowitz and Snell by virtue of its differential activity in promoting growth of certain lactic acid bacteria. It is probable that pyridoxine-5-phosphate also occurs naturally, since it is both formed and oxidized to pyridoxal-5-phosphate by tissue enzymesi -. An unidentified conjugate of pyridoxine also occurs in cereal grains - . 

Pyridoxal Phosphate, Codecarboxylase. An independent approach to the nature of the amino acid decarboxylases was made by Gunsalus, Umbreit, and collaborators. They found that the production of tyrosine decarboxylase by Streptococcus faecalis depended on the vitamin, pyri-doxine. In the absence of pyridoxine the cells grew but had little decarboxylase. However, addition of the vitamin permitted deficient cells to decarboxylate tyrosine, and dried cells exhibited active enzyme in the presence of pyridoxal (a derivative of pyridoxine) and ATP, implying the formation of an active cofactor from these substances. Pyridoxal is a more active growth factor for a strain of Streptococcus faecalis than pyridoxine both synthetic pyridoxal and pyridoxamine exhibit 5000 to 9000 times the activity of the hydroxy compound. ... 

In the tissues, vitamin Be occurs predominantly as the phosphate of pyridoxal or pyridoxamine, especially the former, except in the liver. Pyri-doxal phosphate functions as a coenzyme in four types of reactions decarboxylation of amino acids, transamination, and the synthesis and cleavage of tryptophan (Chapter 19). This coenzyme is necessary for the deamination of amino acids and for the formation of urea nitrogen. It appears to be essential for the conversion of tryptophan to the pyridine coenzymes. Pyridoxine may be related to fatty acid metabolism and seems to be necessary for normal adrenal cortical function. ... 

Fears have been expressed [510, 511] that long-term administration of L-dopa may induce a state of pyridoxine deficiency, since excess dietary pyridoxine, which is rapidly converted in vivo to the decarboxylase coenzyme pyridoxine-5 -phosphate [512], can nullify the beneficial effects of the amino acid [513-515]. Pyridoxine apparently both complexes with L-dopa and produces an accelerated decarboxylation of the amino acid in extracerebral tissues, both processes effectively reducing the amount of available dopamine in the striatum [512, 516]. The decarboxylase inhibitor MK-485 (37) prevents this reversal of the therapeutic effect by pyridoxine [517] and, more significantly, pyridoxine actually enhances the effects of L-dopa when given in conjunction with such an inhibitor [518]. The mechanism involved in this potentiation reflects enhancement by pyridoxine of dopa decarboxylase activity within the striatum in the presence of complete inhibition of extracerebral decarboxylase. The use of combinations of L-dopa, pyridoxine, and inhibitors of aromatic L-amino-acid decarboxylase, may lead to a more... 

Thus a thiamine derivative plays a metabolic role as cocarboxylase, which has been found to be inactivated by a specific phosphatase of yeast (122,123). The inactivation was inhibited by thiamine itself and to a lesser degree by thiamine monophosphate and the pyrimidine constituent of the thiamine molecule. Synthesis and breakdown of thiamine by Phycomyces species have also been studied (9,45,98). Pyridoxine derivatives are now known to catalyze two t3T)cs of bacterial reactions, involving transamination and decarboxylation of amino acids (4,32,35,59). Interconversion between members of the group of substances of natural occurrence which are related to pyridoxine has been observed in microorganisms and appears likely to afford a series of changes comparable to those observed in nicotinic acid dreivatives. Production of folic acid from chemically defined precursors by bacterial suspensions has also been observed (110,111). 

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