Vitamins pyridoxal

Chemical Name Pyridoxine Chemical Abstracts Services Registry Numbers CAS 58-56-0 CAS 65-23-6 Synonyms Vitamin Pyridoxal Pyridoxamine Adermine hydrochloride 3,4-Pyridinedimethanol 5-Hydroxy-6-methyl hydrochloride Chemical/Pharmaceutical/Other Class Water-soluble vitamin... 

The B0 vitamins (pyridoxal, pyridoxamine, and pyridoxine and their phos-phorylated forms, which are the coenzymes) are involved in the transfer of amino groups from one molecule to another, an important step in the biosynthesis of amino acids (Figure 7.20). In the reaction, the amino group is transferred from the donor to the coenzyme and then from the coenzyme to the ultimate acceptor (Figure 7.21). 

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. 

T.J. Hartman, K. Woodson, R. Stolzenberg-Solomon, J. Virtamo, J. Selhub, M.J. Barrett, and D. Albanes. Association of the B vitamins, pyridoxal 5 -phosphate, B[2, and folate with lung cancer risk in older men. Am. J. Epidemiol. 153 688-693 (2001). 

The sequence begins with formation of an imine from the amino acid and the oxidized form of the vitamin, pyridoxal. This imine converts to an isomer via tautomerism simultaneous proton and double-bond shift (See Sections 13-7 and 13-8). Hydrolysis of the new imine gives pyridoxamine and the ketoacid. Depending on the body s metabolic needs, the pyridoxaniine thus formed may proceed to react with other ketoacids to produce required amino acids (the scheme shown above run in reverse), or it may serve to facilitate the ultimate disposal of the nitrogen by excretion. 

The related compounds pyridoxamine and pyridoxal, in which the CH2OH group in the 4-position is replaced by CH2NH2 and CHO respectively, also possess vitamin activity and for certain bacteria are much more active than pyridoxine. 

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... 

Over 250 analogues of the B vitamers have been reported (11,100). Nearly all have low vitamin B activity and some show antagonism. Among these are the 4-deshydroxy analogue, pyridoxine 4-ethers, and 4-amino-5-hydroxymeth5i-2-methyipyrimidine, a biosynthetic precursor to thiamine. StmcturaHy unrelated antagonists include dmgs such as isoniazid, cycloserine, and penicillamine, which are known to bind to pyridoxal enzyme active sites (4). 

Pyridoxal hydrochloride, pyridoxamine hydrochloride and pyridoxine hydrochloride (vitamin Bg) see entries in Chapter 6. 

The biologically active form of vitamin Bg is pyridoxal-5-phosphate (PEP), a coenzyme that exists under physiological conditions in two tautomeric forms (Figure 18.25). PLP participates in the catalysis of a wide variety of reactions involving amino acids, including transaminations, a- and /3-decarboxylations, /3- and ") eliminations, racemizations, and aldol reactions (Figure 18.26). Note that these reactions include cleavage of any of the bonds to the amino acid alpha carbon, as well as several bonds in the side chain. The remarkably versatile chemistry of PLP is due to its ability to... 

Goldberger and Lillie in 1926 found that rats fed certain nutritionally deficient diets developed dermatitis acrodynia, a skin disorder characterized by edema and lesions of the ears, paws, nose, and tail. Szent-Gyorgyi later found that a factor he had isolated prevented these skin lesions in the rat. He proposed the name vitamin Bg for his factor. Pyridoxine, a form of this vitamin found in plants (and the form of Bg sold commercially), was isolated in 1938 by three research groups working independendy. Pyridoxal and pyridoxamine, the forms that predominate in animals, were... 

The ultraviolet spectrum of vitamin Be, or pyridoxine, measured in aqueous ethanol varies with the composition of the solvent indicating that this compound is in equilibrium with the zwitterion form 38. The equilibrium constant in pure water was obtained by extrapolation. Prior to this, equilibria which involved tautomers of type 39 had been suggested for vitamin Be, but see Section VI,A. In the case of pyridoxal, an additional equilibrium, 40 41, occurs (cf. Section VIII) other pyridoxal analogs have also been studied (Table II). 

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. 

Vitamin B6. Figure 1 Structure of pyridoxin, pyridoxal, pyridoxamine, and the coenzymes pyridoxal-5 -phosphate and pyridoxamine-5Y-phosphate. 

When taking levodopa, avoid vitamin B6 (pyridox-ine) because diis vitamin may interfere with the action of levodopa (see Home Care Checklist Avoiding Certain Foods While Taking Levodopa). 

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. 

Lequea et al. used the activity of tyrosine apodecarboxylase to determine the concentration of the enzyme cofactor pyridoxal 5 -phosphate (vitamin B6). The inactive apoenzyme is converted to the active enzyme by pyridoxal 5 -phosphate. By keeping the cofactor the limiting reagent in the reaction by adding excess apoenzyme and substrate, the enzyme activity is a direct measure of cofactor concentration. The enzymatic reaction was followed by detecting tyramine formation by LCEC. The authors used this method to determine vitamin B6 concentrations in plasma samples. 

Vitamin Bg and related compoimds (Figure 10.2) were quantitatively separated by preparative TLC on silica gel H. After elution, the pyridoxic acid lactone method was employed for fluorimetric determination of the concentration of the vitamin forms involved [8]. Table 10.2 shows Revalues obtained for various forms of vitamin Bg, using several solvent systems. The solvent selected, ethyl acetate/pyridine/water (2 1 2, v/v), gave excellent separation of pyridoxamine, pyridoxic acid, and pyri-doxine together with pyridoxal. 

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