Coenzyme Activity
The active form of pyridoxine is the coenzyme pyridoxal phosphate. The phosphates' of pyridoxine and of pyridoxamine are also found naturally.
The synthesis of the coenzyme from pyridoxal. and ATP was demonstrated by Hurwitz: pyridoxal + ATPpyridoxal ~ phosphate + ADP
Human brain is a very rich source of pyridoxal kinase, the phosphorylating enzyme. The enzyme mediated phosphorylation of all three forms of the vitamin and was activated strongly by Zn++.
The ever increasing number of molecular interconversions mediated by pyridoxal phosphatedependent enzymes attests to the significant metabolic role of this vitamin.
The coenzyme is required in the decarboxylation of amino acids. In this function it is referred to as codecar boxylase to distinguish it from cocarboxylase, which is thiamine pyrophosphate, involved in a-keto acid decarboxylations. Some of the amino acid decarboxylases have been studied in detail. Histidine decarboxylase, for example, produces histamine and CO2 from histidinc. The general reaction is
RCHNH2COOH ---> RCH2NH2 + CO2
A number of amino acid derivatives not found in proteins are also decarboxylated by enzymes requiring pyridoxal phosphate. An example of this is the demonstration by Weissbach and co-workers of the functional role of the coenzyme in the decarboxylation of 5-hydroxytryptophan with the production of 5-hydroxytryptamine (serotonin) plus CO2, Another step in tryptophan metabolism involves the pyridoxal phosphate-dependent enzyme kinureninase, which catalyzes the conversion of kynurenine to anthranilic acid.
Cysteinesulfinic acid decarboxylase is another, example of a decarboxylase using a nonprotein amino acid as substrate. In general the amino acid decarboxylases are highly specific and can be used in the determination of various amino acids by following CO2 production in purified systems. The wide scope of amino acid transamination reactions was established by Cammarata and Cohen, who studied 22 transaminase reactions in animal tissues and suggested
. that each involved a distinct enzyme with pyridoxal phosphate as, coenzyme. Typical of these enzymes is glutamic-oxalacetic transaminase (glutamicaspartic transaminase) which mediates the reaction
glutamate + oxalacetate ---> a-ketoglufarate + aspartate
Diamine oxidase brings about oxidative deamination of certain diamines, such as cadaverine. Pig kidney histaminase and diamine oxidase appear to be identical, with pyridoxal phosphate as coenzyme in both cases. Cysteine desulfuydrase is another pyridoxal phosphate enzyme. It converts cysteine to pyruvate and H2S + NH3'
A number of dehydrases found in animal tissues require pyridoxal phosphate and remove water from hydroxy amino acids. Examples are serine dehydrase (yields pyruvate and NH3 + H20) and threonine dehydrase (yields a-ketobutyric acid and NH3 + H20). The coenzyme is required, among other factors, in the synthesis of o-amino levulinic acid, a requisite intermediate in porphyrin synthesis. An interesting role of the coenzyme is found in bacterial enzymes responsible for racemization of certain amino acids. For instance, S. faecalis requires D-alanine for cell wall construction.
The organism can convert L-alanine to the D form, providing pyridoxal phosphate is supplied, since this is the coenzyme of alanine racemase. The presence of 4 mols of pyridoxal phosphate per mol of phosphorylase-a and 2 mols per mol of phosphorylase-b was reported by Cori and Illingsworth . The significance of the presence of the coenzyme in this system is not clear. Human muscle phosphorylase-b contains 2 mols of pyridoxal phosphate and phosphorylase-a 4 mols on the basis of a molecular weight of 250,000 for the b and 500,000 for the a. From the foregoing it is clear that the pyridoxine-active compounds are associated with most of the nonoxidative metabolic changes of amino acids, and with some pathways not involving amino acids.
Further details and proposed mechanisms of action of pyridoxal phosphate enzymes can be found in. Pyridoxine and pyridoxamine can be converted in the body to pyridoxal. An enzyme system in rat liver catalyzes the oxidation of pyridoxamine or its phosphate to pyridoxal or the phosphate. An example of a biochemical deficiency related to a functional role of a vitamin or coenzyme is the decreased production of taurocholic acid in B6 deficient rats, Doisy and co-workers showed that dietary correction resulted in increased production of this bile salt. Pyridoxal phosphate is required in the enzyme system catalyzing the decarbcxylation of cysteine sulfonic acid which is a source of taurine. The latter compound reacts with cholic acid to form taurocholic acid. A decreased activity of specific transaminase enzymes in a B6 deficiency would be expected. This has been demonstrated in various species. Glutamicaspartic transaminase was decreased in deficient rats. In a deficiency state the decreased transaminase activity of tissues shunts greater amounts of amino acids into other metabolic pathways, such as deamination, accounting for the increased urea production under these conditions.
The active form of pyridoxine is the coenzyme pyridoxal phosphate. The phosphates' of pyridoxine and of pyridoxamine are also found naturally.
The synthesis of the coenzyme from pyridoxal. and ATP was demonstrated by Hurwitz: pyridoxal + ATPpyridoxal ~ phosphate + ADP
Human brain is a very rich source of pyridoxal kinase, the phosphorylating enzyme. The enzyme mediated phosphorylation of all three forms of the vitamin and was activated strongly by Zn++.
The ever increasing number of molecular interconversions mediated by pyridoxal phosphatedependent enzymes attests to the significant metabolic role of this vitamin.
The coenzyme is required in the decarboxylation of amino acids. In this function it is referred to as codecar boxylase to distinguish it from cocarboxylase, which is thiamine pyrophosphate, involved in a-keto acid decarboxylations. Some of the amino acid decarboxylases have been studied in detail. Histidine decarboxylase, for example, produces histamine and CO2 from histidinc. The general reaction is
RCHNH2COOH ---> RCH2NH2 + CO2
A number of amino acid derivatives not found in proteins are also decarboxylated by enzymes requiring pyridoxal phosphate. An example of this is the demonstration by Weissbach and co-workers of the functional role of the coenzyme in the decarboxylation of 5-hydroxytryptophan with the production of 5-hydroxytryptamine (serotonin) plus CO2, Another step in tryptophan metabolism involves the pyridoxal phosphate-dependent enzyme kinureninase, which catalyzes the conversion of kynurenine to anthranilic acid.
Cysteinesulfinic acid decarboxylase is another, example of a decarboxylase using a nonprotein amino acid as substrate. In general the amino acid decarboxylases are highly specific and can be used in the determination of various amino acids by following CO2 production in purified systems. The wide scope of amino acid transamination reactions was established by Cammarata and Cohen, who studied 22 transaminase reactions in animal tissues and suggested
. that each involved a distinct enzyme with pyridoxal phosphate as, coenzyme. Typical of these enzymes is glutamic-oxalacetic transaminase (glutamicaspartic transaminase) which mediates the reaction
glutamate + oxalacetate ---> a-ketoglufarate + aspartate
Diamine oxidase brings about oxidative deamination of certain diamines, such as cadaverine. Pig kidney histaminase and diamine oxidase appear to be identical, with pyridoxal phosphate as coenzyme in both cases. Cysteine desulfuydrase is another pyridoxal phosphate enzyme. It converts cysteine to pyruvate and H2S + NH3'
A number of dehydrases found in animal tissues require pyridoxal phosphate and remove water from hydroxy amino acids. Examples are serine dehydrase (yields pyruvate and NH3 + H20) and threonine dehydrase (yields a-ketobutyric acid and NH3 + H20). The coenzyme is required, among other factors, in the synthesis of o-amino levulinic acid, a requisite intermediate in porphyrin synthesis. An interesting role of the coenzyme is found in bacterial enzymes responsible for racemization of certain amino acids. For instance, S. faecalis requires D-alanine for cell wall construction.
The organism can convert L-alanine to the D form, providing pyridoxal phosphate is supplied, since this is the coenzyme of alanine racemase. The presence of 4 mols of pyridoxal phosphate per mol of phosphorylase-a and 2 mols per mol of phosphorylase-b was reported by Cori and Illingsworth . The significance of the presence of the coenzyme in this system is not clear. Human muscle phosphorylase-b contains 2 mols of pyridoxal phosphate and phosphorylase-a 4 mols on the basis of a molecular weight of 250,000 for the b and 500,000 for the a. From the foregoing it is clear that the pyridoxine-active compounds are associated with most of the nonoxidative metabolic changes of amino acids, and with some pathways not involving amino acids.
Further details and proposed mechanisms of action of pyridoxal phosphate enzymes can be found in. Pyridoxine and pyridoxamine can be converted in the body to pyridoxal. An enzyme system in rat liver catalyzes the oxidation of pyridoxamine or its phosphate to pyridoxal or the phosphate. An example of a biochemical deficiency related to a functional role of a vitamin or coenzyme is the decreased production of taurocholic acid in B6 deficient rats, Doisy and co-workers showed that dietary correction resulted in increased production of this bile salt. Pyridoxal phosphate is required in the enzyme system catalyzing the decarbcxylation of cysteine sulfonic acid which is a source of taurine. The latter compound reacts with cholic acid to form taurocholic acid. A decreased activity of specific transaminase enzymes in a B6 deficiency would be expected. This has been demonstrated in various species. Glutamicaspartic transaminase was decreased in deficient rats. In a deficiency state the decreased transaminase activity of tissues shunts greater amounts of amino acids into other metabolic pathways, such as deamination, accounting for the increased urea production under these conditions.
