Pyridoxine 5-phosphate, oxidation

Although pyridoxine is taken up and phosphorylated by muscle (and other tissues), the resultant pyridoxine phosphate is not oxidized to pyridoxal phosphate. It has been suggested that the neurotoxicity of high intakes of pyridoxine (Section 9.9.6.4) may be caused by the uptake and trapping of pyridoxine, and hence competition with pyridoxal, resulting in depletion of tissue pyridoxal phosphate and a deficiency of the metabolically active form of the vitamin. 

The predominant circulating form of vitamin Bg is pyridoxal phosphate. Absorbed pyridoxine is oxidized and phosphorylated in intestinal mucosal cells, liver, and erythrocytes. Pyridoxine enters hepatocytes and erythrocytes by passive diffusion and is mostly retained by phosphorylation. Pyridoxal phosphate is transported in the blood bound to albumin. The blood-brain barrier has limited permeability to pyridoxal. 

Studies based on the use of an antivitamin, deoxypyri-doxine, have established that the daily requirement of the vitamin ranges between 1 and 2 mg in the human adult. A normal diet has been reported to provide 1-1.5 mg daily of the vitamin. Food appears to be the only source of the vitamin because most of the vitamin produced by the bacterial flora of the intestine is excreted in the feces, possibly after oxidation to 4-pyridoxic acid. The ingested vitamin is rapidly and completely absorbed, but the exact site of the absorption is not known. Although both pyridoxine and pyridoxamine can be excreted as such and are therefore normal constituents of human urine, part of the vitamin is oxidized to the 4-pyridoxic acid before excretion in the urine. Mammalian tissues contain at least two enzymes capable of oxidizing pyridoxine. Both enzymes seem to be flavoproteins. One attacks pyridoxine, the other attacks pyridoxine phosphate. The pyridoxine phosphate oxidase of liver has been purified 65 times. Although the enzyme was shown to act on pyridoxamine phosphate, pyridoxamine phosphate was oxidized only when the pH of the incubation mixture was raised to 10. Pyridoxine phosphate oxidase has no effect on pyridoxamine phosphate at physiological pH. 

Pyridoxine phosphate may either be used unchanged in enzymic reactions, or it may be split by nonspecific phosphatases to yield pyridoxine and inorganic phosphate. Pyridoxine is then further oxidized to yield 4-pyridoxic acid in the presence of a purified preparation of liver pyridoxic oxidase and aldehyde oxidase. 

Infusion solutions of pyridoxine (274) hydrochloride were unaffected by ward lighting, but when riboflavine phosphate sodium was added the pyridoxine was completely decomposed in about 3 h. The photosensitized oxidation gave... 

Two vitamins, nicotinamide and pyridoxine (vitamin B6), are pyridine derivatives. Nicotinamide participates in two coenzymes, coenzyme I (65 R = H) which is known variously as nicotinamide adenine dinucleotide (NAD) or diphosphopyridine nucleotide (DPN), and coenzyme II (65 R = P03H2) also called triphosphopyridine nucleotide (TPN) or nicotinamide adenine dinucleotide phosphate (NADP). These are involved in many oxidation-reduction processes, the quaternized pyridine system acting as a hydrogen acceptor and hydrogen donor. Deficiency of nicotinamide causes pellagra, a disease associated with an inadequately supplemented maize diet. Nicotinic acid (niacin) and its amide are... 

Some enzymes require additional chemical species, called cofactors or coenzymes, to be fully active. Cofactors include metal ions such as Fe+2, Zn+2, and Cu+2. Coenzymes are organic molecules that allow transfer of functional groups or reduction/oxidation reactions. Examples include thiamine pyrophosphate (4.6) and pyridoxine 5 -phosphate (4.7) (Figure 4.8). 

Wada and Snell (150) have developed a method for the assay of pyridoxine and pyridoxamine phosphate, based on enzymatic oxidation to pyridoxal which is allowed to react with phenylhydrazine. 

Three enzymes play an active role in the metabolism of vitamin B6 in human erythrocytes. Pyridoxal kinase uses ATP to phosphorylate pyridoxine, pyri-doxamine, and pyridoxal. Pyridoxamine oxidase oxidizes pyridoxamine-5 -phosphate and pyridoxine-5 -phosphate to pyridoxal-5 -phosphate. The phosphatase activity produces pyridoxal from pyridoxal-5 -phosphate. The assay of the three enzymes required separation of the semicarbazone derivatives of pyridoxal-5 -phosphate and pyridoxal. The mobile phase used by Ubbink and Schnell (1988) contained 2.5% acetonitrile. Detection was by fluorescence. 

Be and for the biosynthesis of isoprenoids via the nonmeval-onate pathway. Condensation of 43 with 3-amino-l-hydroxy-acetone phosphate (47) (biosynthesized from D-erythrose 4-phosphate) affords pyridoxine 5 -phosphate (48, Fig. 5A). A sequence of elimination, tautomerization, and water addition precedes cyclization via an aldol condensation (26, 27). Then, pyridoxine 5 -phosphate can be converted into pyridoxal 5 -phosphate (39) by oxidation with molecular oxygen. 

An early procedure which alfords a quick if inefficient route to toluquinone consists in steam distillation of a mixture of o-toluidine, manganese dioxide, and sulfuric acid. The reagent has been used to oxidize pyridoxine (1) to pyridoxal 2f and to oxidize pyridoxamine phosphate (3) to pyridoxal phosphate (4). ... 

Potassium Bitartrate Potassium Carbonate Potassium Hydroxide Potassium Nitrate Potassium Sulfate Pyridoxine Retinol Riboflavin Saccharin Silicon Dioxide Silver Nitrate Silver(I) Oxide Sodium Acetate Sodium Bicarbonate Sodium Carbonate Sodium Cyclamate Sodium Hydroxide Sodium Hypochlorite Sodium Perborate Sodium Phosphate Sodium Polyacrylate Sodium Silicate Sodium Sulfite Sodium Tetraborate Sodium Thiosulfate Sucrose... 

Hydrolysis of pyridoxal phosphate to pyridoxal followed by oxidation to 4-pyridoxic acid is the major catabolic pathway for vitamin B6 in most mammalian species. In cats, however, the major urinary metabolites are pyridoxine 3-sulfate and N-methylpyridoxine (Cobum and Mahuren, 1987). Also, in humans receiving very large vitamin B6 intakes excretion of 5-pyridoxic acid may become significant (Mahuren et aL, 1991). 

The major sales form of vitamin B6 is the hydrochlorid salt of the primary alcohol pyridoxine. Another vitamin B6 form introduced in the market is the dihydrochlo-rid salt of pyridoxamine. Both vitamin B6 forms are commercially produced via various straightforward chemical synthesis routes. The biologically active cofactor is the aldehyde pyridoxal-5 -phosphate, which is derived in human or animals from the vitamin B6 forms by oxidation or transamination before or after 5 phosphorylation by pyridoxal kinases. 

Ingredients Calcium Carbonate, Microcrystalline Cellulose, Magnesium Oxide, Ferrous Fumarate, Ascorbic Acid, Maltodextrin, Gelatin, dl-Alpha-Tocopheryl Acetate, Dicalcium Phosphate Less than 2% of Beta-Carotene, Biotin, Cholecalciferol, Croscarmellose Sodium, Cupric Oxide, Cyanocobalamin, D-Calcium Pantothenate, FD C Red 40 Dye, FD C Red 40 Lake, FD C Yellow 6 Lake, Folic Acid, Hydroxypropyl Methylcellulose, Niacinamide, Polyethylene Glycol, Polysorbate 80, Potassium Iodide, Pyridoxine Flydrochloride, Riboflavin, Silicon Dioxide, Soybean Oil, Starch, Stearic Acid, Thiamine Mononitrate, Titanium Dioxide (color), Vitamin A Acetate, Zinc Oxide... 

In the first path, the PLP precursor pyridoxine 5-phosphate (PNP) is biosynthesized from 3-hydroxy-1-aminoacetone phosphate 1 and DXP 2 (Figure 6.1). DXP 2 is formed from pyruvate 3 and glyceraldehyde 3-phosphate 4, catalyzed by deoxy-D-xylulose 5-phosphate synthase (DXS). The 3-hydroxy-1-aminoacetone phosphate 1 is obtained from the erythrose 4-phosphate 5 in four steps. The first step involves the oxidation of erythrose 4-phosphate 5, mediated by erythrose 4-phosphate dehydrogenase (GapB), to erythronate 4-phosphate 6. The latter is further oxidized by D-erythronate 4-phosphate dehydrogenase (PdxB) to 3-hydroxy-4-phosphohydroxy-a-ketobutyrate 7. Transamination reaction between... 

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, pyridoxamine and pyridoxine are interconvertible in animal tissues, and all are converted to the functional forms, pyridoxal phosphate and pyridoxamine phosphate. Excessive amounts of the vitamin over and above tissue requirements are excreted, in part unchanged and in part after oxidation to 4-pyridoxic acid. Several soil micro-organisms, chiefly pseudomonads, have been isolated that grow on various forms of vitamin Be as a sole source of carbon, nitrogen and energy. Compounds listed in pathways A and B, Fig. 5, have been isolated as intermediates formed during oxidation of the vitamin to COa and water by two different species of these organ-isms - . 

STEP 7 OF FIGURE 25.1 OXIDATION The final step in PLP biosynthesis is oxidation of the primary alcohol group in pyridoxine 5 -phosphate to the corresponding aldehyde. Typically, as we ve seen on numerous occasions, alcohol oxidations are carried out hy either NAD" " or NADP+. In this instance, however, flavin mononucleotide (FMN) is involved as the oxidizing coenzyme and reduced flavin mononucleotide (FMNH2) is the hy-product. The details of the reaction are not clear, but evidence suggests that a hydride transfer is involved, just as in NAD" " oxidations. 

PMP) and pyridoxine-5 -phosphate (PNP) are also widely distributed in animal and plant tissues. Glycosylated forms of pyridoxine are commonly found in plants (8). The major glycosylated form of vitamin in plants is 5 -0-p-D glucopyra-nosyl pyridoxine (PN-glucoside) (8). The oxidized metabolites of pyridoxal, 3-hydroxy-5-hydroxymethyl-2-methylpyridine-4-carboxylic acid, and the corresponding lactone are designated 4-pyridoxic acid (4-PA) and 4-pyridoxolactone (4-PA lactone), respectively. 

H Wada, EE Snell. The enzymatic oxidation of pyridoxine and pyridoxamine phosphates. J Biol Chem 236 2089-2095, 1961. 

Both pyridoxal and the phosphate circulate in the bloodstream the phosphate is dephosphorylated by extracellular alkaline phosphatase, and tissues take up pyridoxal by carrier-mediated diffusion, followed by metabolic trapping as phosphate esters. Pyridoxine and pyridoxamine phosphates are oxidized to pyridoxal phosphate (Figure 1). 

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