Vitamin pyridoxal phosphate

Equation (1) indicates that a low heme content may be due to a lack of the two vitamins, pyridoxal phosphate and CoA, which are required for the limiting step in porphyrin biosynthesis. The smallness of the red cells in pyridoxal phosphate deficiency is probably due not only to the necessity of this coenzyme for amino acid and heme synthesis, but also to the fact that, without heme, globin is not synthesized. 

An example of a biologically important aide hyde is pyridoxal phosphate which is the active form of vitamin Bg and a coenzyme for many of the reac tions of a ammo acids In these reactions the ammo acid binds to the coenzyme by reacting with it to form an imine of the kind shown in the equation Re actions then take place at the ammo acid portion of the imine modifying the ammo acid In the last step enzyme catalyzed hydrolysis cleaves the imme to pyridoxal and the modified ammo acid... 

Pyridoxal phosphate, a close relative of vitamin B6, is involved in a large number of metabolic reactions. TeJl the hybridization, and predict the bond angles for each nonterminal atom. 

Most amino acids lose their nitrogen atom by a transamination reaction in which the -NH2 group of the amino acid changes places with the keto group of ct-ketoglutarate. The products are a new a-keto acid plus glutamate. The overall process occurs in two parts, is catalyzed by aminotransferase enzymes, and involves participation of the coenzyme pyridoxal phosphate (PLP), a derivative of pyridoxine (vitamin UJ. Different aminotransferases differ in their specificity for amino acids, but the mechanism remains the same. 

In general, pyridoxamine and pyridoxin are more stable than pyridoxal. All vitamers are relatively heat-stable in acid media, but heat labile in alkaline media. All forms of vitamin B6 are destroyed by UV light in both neutral and alkaline solution. The majority of vitamin B6 in the human body is stored in the form of pyridoxal phosphate in the muscle, bound to glycogen phos-phorylase. 

Muscle phosphorylase is distinct from that of Hver. It is a dimer, each monomer containing 1 mol of pyridoxal phosphate (vitamin Bg). It is present in two forms phos-phoiylase a, which is phosphorylated and active in either the presence or absence of 5 -AMP (its allosteric modifier) and phosphorylase h, which is dephosphorylated and active only in the presence of 5 -AMP. This occurs during exercise when the level of 5 -AMP rises, providing, by this mechanism, fuel for the muscle. Phosphorylase a is the normal physiologically active form of the enzyme. 

Six compounds have vitamin Bg activity (Figure 45-12) pyridoxine, pyridoxal, pyridoxamine, and their b -phosphates. The active coenzyme is pyridoxal 5 -phos-phate. Approximately 80% of the body s total vitamin Bg is present as pyridoxal phosphate in muscle, mostly associated with glycogen phosphorylase. This is not available in Bg deficiency but is released in starvation, when glycogen reserves become depleted, and is then available, especially in liver and kidney, to meet increased requirement for gluconeogenesis from amino acids. 

Pyridoxal phosphate is a coenzyme for many enzymes involved in amino acid metabolism, especially in transamination and decarboxylation. It is also the cofactor of glycogen phosphorylase, where the phosphate group is catalytically important. In addition, vitamin Bg is important in steroid hormone action where it removes the hormone-receptor complex from DNA binding, terminating the action of the hormones. In vitamin Bg deficiency, this results in increased sensitivity to the actions of low concentrations of estrogens, androgens, cortisol, and vitamin D. 

The most widely used method of assessing vitamin Bg status is by the activation of erythrocyte aminotransferases by pyridoxal phosphate added in vitro, expressed as the activation coefficient. 

By contrast, the cytoplasmic decarboxylation of dopa to dopamine by the enzyme dopa decarboxylase is about 100 times more rapid (Am 4x 10 " M) than its synthesis and indeed it is difficult to detect endogenous dopa in the CNS. This enzyme, which requires pyridoxal phosphate (vitamin B6) as co-factor, can decarboxylate other amino acids (e.g. tryptophan and tyrosine) and in view of its low substrate specificity is known as a general L-aromatic amino-acid decarboxylase. 

If a vitamin or cofactor is involved in amino acid metabolism, it s most likely pyridoxal phosphate (B6), unless it involves serine, and then it s B6 and folic acid. 

These enzymes invariably involve a cofactor, pyridoxal phosphate (vitamin B6). In addition, pyridoxal phosphate is also required for most decarboxylations, racemizations, or elimination reactions in which an amino acid is a substrate. Pyridoxal phosphate is not involved in decarboxylations in which the substrate is not an amino acid. So if a question... 

Homocystinuria can be treated in some cases by the administration of pyridoxine (vitamin Bs), which is a cofactor for the cystathionine synthase reaction. Some patients respond to the administration of pharmacological doses of pyridoxine (25-100 mg daily) with a reduction of plasma homocysteine and methionine. Pyridoxine responsiveness appears to be hereditary, with sibs tending to show a concordant pattern and a milder clinical syndrome. Pyridoxine sensitivity can be documented by enzyme assay in skin fibroblasts. The precise biochemical mechanism of the pyridoxine effect is not well understood but it may not reflect a mutation resulting in diminished affinity of the enzyme for cofactor, because even high concentrations of pyridoxal phosphate do not restore mutant enzyme activity to a control level. 

The leucocyte method estimates pyridoxal phosphate in isolated leucocytes it is based on a coenzyme-catalyzed tyrosine decarboxylase system from S. faecalis (B32). Enough data are not yet on hand to evaluate this method. The determination of circulating or available vitamin Ba should offer a more direct approach. 

Group-transfer reactions often involve vitamins3, which humans need to have in then-diet, since we are incapable of realizing their synthesis. These include nicotinamide (derived from the vitamin nicotinic acid) and riboflavin (vitamin B2) derivatives, required for electron transfer reactions, biotin for the transfer of C02, pantothenate for acyl group transfer, thiamine (vitamin as thiamine pyrophosphate) for transfer of aldehyde groups and folic acid (as tetrahydrofolate) for exchange of one-carbon fragments. Lipoic acid (not a vitamin) is both an acyl and an electron carrier. In addition, vitamins such as pyridoxine (vitamin B6, as pyridoxal phosphate), vitamin B12 and vitamin C (ascorbic acid) participate as cofactors in an important number of metabolic reactions. 

The role of pyridoxal phosphate (vitamin Bg), which is enzyme bound, is to hold the amino group once it leaves the donor and before being incorporated into the acceptor (Figure 6.3). 

As indicated in Section 6.3.3 and Table 6.2 the key control step is mediated by glycogen phosphorylase, a homodimeric enzyme which requires vitamin B6 (pyridoxal phosphate) for maximum activity, and like glycogen synthase (Section 6.2) is subject to both allosteric modulation and covalent modification. 

Muscle glycogen phosphorylase is one of the most well studied enzymes and was also one of the first enzymes discovered to be controlled by reversible phosphorylation (by E.G. Krebs and E. Fischer in 1956). Phosphorylase is also controlled allosterically by ATP, AMP, glucose and glucose-6-phosphate. Structurally, muscle glycogen phosphorylase is similar to its hepatic isoenzyme counterpart composed of identical subunits each with a molecular mass of approximately 110 kDa. To achieve full activity, the enzyme requires the binding of one molecule of pyridoxal phosphate, the active form of vitamin B6, to each subunit. 

Require pyridoxal phosphate (PLP) derived from vitamin... 

Both muscle and liver have aminotransferases, which, unlike deaminases, do not release the amino groups as free ammonium ion. This class of enzymes transfers the amino group from one carbon skeleton (an amino acid) to another (usually a-ketoglutarate, a citric acid cycle intermediate). Pyridoxal phosphate (PLP) derived from vitamin is required to mediate the transfer. 

Vitamin B6 pyridoxal phosphate chemical, biomedical, and medical aspects, Part A. 

The cases of myoglobin and hemoglobin are not rare. Many enzymes are dependent for their function on the presence of a nonprotein group. For example, cytochrome c also contains a prosthetic group similar, but not identical, to heme, as do a number of other proteins. These are known generically as heme proteins. There is a family of enzymes that contain a flavin group, the flavoproteins. Another family contains pyridoxal phosphate, a derivative of vitamin Be. There are a number of other examples. 

The vitamin Be family of molecules are metabolic precursors to pyridoxal phosphate, an essential coenzyme for multiple enzymes involved in amino acid metabolism. 

Vitamin Bg a family of molecules having vitamin Be activity these include pyridoxal, pyridoxine, and pyridoxamine precursors to the coenzyme pyridoxal phosphate. 

We have just noted the role that pyridoxal phosphate plays as a coenzyme (cofactor) in transamination reactions (see section 15.6). Pyridoxal 5 -phosphate (PLP) is crucial to a number of biochemical reactions. PLP, together with a number of closely related materials that are readily converted into PLP, e.g. pyridoxal, pyridoxine and pyridoxamine, are collectively known as vitamin Bg, which is essential for good health. 

The active form of vitamin Be, pyridoxai phosphate, is the most important coenzyme in the amino acid metabolism (see p. 106). Almost all conversion reactions involving amino acids require pyridoxal phosphate, including transaminations, decarboxylations, dehydrogenations, etc. Glycogen phosphory-lase, the enzyme for glycogen degradation, also contains pyridoxal phosphate as a cofactor. Vitamin Be deficiency is rare. 

Pyridoxine (vitamin 65) deficiency sometimes is observed in adults taking high doses of INH and is probably caused by the drug s competition with pyridoxal phosphate for the enzyme apotryptophanase. 

Pyridoxine (vitamin Bg, 18) (Fig. 13) assists in the balancing of sodium and potassium as well as promoting red blood cell production. A lack of pyridoxine can cause anemia, nerve damage, seizures, skin problems, and sores in the mouth. It is required for the production of the monoamine neurotransmitters serotonin, dopamine, norepinephrine, and epinephrine, as it is the precursor to pyridoxal phosphate, which is the cofactor for the aromatic amino acid decarboxylase enzyme. 

Vitamin Bg is a mixture of six interrelated forms pyridoxine (or pyridoxol) (Figure 19.23), pyri-doxal, pyridoxamine, and their 5 -phosphates derivatives. Interconversion is possible between all forms. The active form of the vitamin is pyridoxal phosphate, which is a coenzyme correlated with the function of more than 60 enzymes involved in transamination, deamination, decarboxylation, or desulfuration reactions. 

Vitamin B deficiency is a rare condition, but it is prevalent in persons with chronic alcoholism due to low dietary Intake and impaired conversion ofpyridoxine to the active coenzyme pyridoxal phosphate. 

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