Pyridoxine, structure

Observations on the activity of pyridoxin mid closely related compounds with a variety of different types of organism are collected in Table XI. The results show the high biological specificity of the pyridoxin structure... 

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

FIGURE 10.2 Structural formula of vitamin and related compounds. 1 — pyridoxine, 2 — pyridoxal, 3 — pyridoxamine, 4 — 4-pyridoxic acid 5 — pyridoxal-5 -phosphate. 

Lactobacillus delbrueckii. In 1953, Rodwell suggested that the histidine decarboxylase of Lactobacillus 30a was not dependent upon pyridoxal phosphate (11). Rodwell based his suggestion upon the fact that the organism lost its ability to decarboxylate ornithine but retained high histidine decarboxylase activity when grown in media deficient in pyridoxine. It was not until 1965 that E. E. Snell and coworkers (12) isolated the enzyme and showed that it was, indeed, free of pyridoxal phosphate. Further advances in characterization of the enzyme were made by Riley and Snell (13) and Recsei and Snell (14) who demonstrated the existence of a pyruvoyl residue and the participation of the pyruvoyl residue in histidine catalysis by forming a Schiff base intermediate in a manner similar to pyridoxal phosphate dependent enzymes. Recent studies by Hackert et al. (15) established the subunit structure of the enzyme which is similar to the subunit structure of a pyruvoyl decarboxylase of a Micrococcus species (16). 

CNS toxicity occurs because isoniazid has structural similarities to pyridoxine (vitamin Be) and can inhibit its actions. This toxicity is dose-related and more common in slow acetylators. Manifestations include peripheral neuropathy, optic neuritis, ataxia, psychosis and seizures. The administration of pyridoxine to patients receiving INH does not interfere with the tuberculostatic action of INH but it prevents and can even reverse neuritis. Hematological effects include anaemia which is also responsive to pyridoxine. In some 20% of patients antinuclear antibodies can be detected but only in a minority of these patients drug-induced lupus erythematosus becomes manifest. 

Isoniazid (isonicotinic acid hydrazide, or INH) is the most active drug for the treatment of tuberculosis caused by susceptible strains. It is a synthetic agent with a structural similarity to that of pyridoxine. 

As aromatic compounds have been exhausted as building blocks for life science products, A-heterocyclic structures prevail nowadays. They are found in many natural products, such as chlorophyll hemoglobin and the vitamins biotin (H), folic acid, niacin (PP), pyridoxine HCl (Be), riboflavine (B2), and thiamine (Bi). In life sciences 9 of the top 10 proprietary drugs and 5 of the top 10 agrochemicals contain A-heterocycIic moieties (see Tables 11.4 and 11.7). Even modern pigments, such as diphenylpyrazolopyrazoles, quinacri-dones, and engineering plastics, such as polybenzimidazoles, polyimides, and triazine resins, exhibit an A-heterocydic structure. 

Vitamin B6 occurs naturally in three related forms pyridoxine (6.26 the alcohol form), pyridoxal (6.27 aldehyde) and pyridoxamine (6.28 amine). All are structurally related to pyridine. The active co-enzyme form of this vitamin is pyridoxal phosphate (PLP 6.29), which is a co-factor for transaminases which catalyse the transfer of amino groups (6.29). PLP is also important for amino acid decarboxylases and functions in the metabolism of glycogen and the synthesis of sphingolipids in the nervous system. In addition, PLP is involved in the formation of niacin from tryptophan (section 6.3.3) and in the initial synthesis of haem. 

VITAMIN B (Pyridoxine). Infrequently called adermine or pyridoxol, this vitamin participates in protein, carbohydrate, and lipid metabolism. The metabolically active form of B6 is pyridoxal phosphate, the structures of which are ... 

In 1934, Gyorgy cured a dermatitis in rats (not due to vitamins Bj or B2) with a yeast extract factor, In 1938, Lepkovsky isolated a similar factor from nee bran extract. In that same year. Keresztesy and Stevens isolated and crystallized pure (, from rice polishings. Also, in the same year, Kohn, Wendt, and Westphal synthesized pyridoxine and gave pyridoxine its present name. In the following year (1939). Stiller, Keresztesy, and Stevens established the structure of the vitamin, In 194 5, Snell observed pyridoxal and pyridoxamine. The recognition of and establishment of B5 requirements in humans was not achieved until 1953, by Snyderman et al. 

Pyridoxal-5 -phosphate is the coenzyme form of vitamin B6, and has the structure shown in figure 10.3. The name vitamin B6 is applied to any of a group of related compounds lacking the phosphoryl group, including pyridoxal, pyridoxamine, and pyridoxine. 

Isoniazid is bactericidal for growing tubercle bacilli, is absorbed orally, and is metabolized by acetylation. It is a structural analogue of pyridoxine and may cause pyridoxine deficiency, peripheral neuritis and, in toxic doses, pyridoxine-responsive convulsions. Its mechanism of action is not known. 

The FMR spectrum of pyridoxine, HC1 in deuterated water was recorded on a Varian T-60A, 60-MHz NMR spectrometer. The spectrum is shown in Fig. 4. The following structural assignments have been elicited from Fig. 4. 

Pyridoxine, pyridoxal, and pyridoxamine, which occur in foodstuffs, are collectively known as vitamin Bg. In the body, all three are converted to pyridoxal phosphate which is the coenzyme for amino-acid decarboxylase and for transaminase. The structures of the three active forms of vitamin Bg and the pyridoxal phosphate, are shown below (55). 

Fig. 4. Structures of (a) pyridoxine (vitamin Bg), (b) pyridoxal phosphate and (c) pyridoxamine phosphate.

Arrows in vitamin or coenzyme structures indicate active sites. bR in the structure of pyridoxine indicates -CH2OH. 

Vitamins of group B were analysed in different forms [530]. Isopropylidene derivatives showed selectivity of the chromatographic separation which was caused by even minor structural differences. Several compounds from the pyridoxine group can be analysed after their conversion into acetates acetylation followed by GC also appeared suitable for three vitamins and 4-pyridoxic lactone. TMS derivatives were recommended for GC separation of the phosphate form of vitamins. When treated with BSTFA—pyridine (1 1) at 60°C for 15 min, biotin provides a completely silylated derivative, which was analysed on a column packed with 3% of OV-17 [531 ]. 

Hayon and co-workers have studied, by pulse radiolysis, 1-hydropyridinyl radicals ranging from those formed from simple C-acylpyridines to those from pyridoxine and pyridoxal phosphate.210-212 Structural, spectroscopic, kinetic, and thermodynamic data have been presented. Various mechanisms have been adduced which involve 35 and analogous species from quinolines,... 

A second clue to the catalytic mechanism of phosphorylase is its requirement for pyridoxal phosphate (PLP), a derivative of pyridoxine (vitamin B5, Section 8.6.1). The aldehyde group of this coenzyme forms a Schiff base with a specific lysine side chain of the enzyme (Figure 21.7). The results of structural studies indicate that the reacting... 

Isoniazid is a structural analogue of pyridoxine and accelerates its excretion, the principal result of which is peripheral neuropathy with numbness and tingling of the feet, motor involvement being less common. Neuropathy is more frequent in slow acetylators, malnourished people, the elderly and those with HIV infection, liver disease and alcoholism. Such patients should receive pyridoxine lOmg/d by mouth, which prevents neuropathy and does not interfere with the therapeutic effect some prefer simply to give pyridoxine to all patients. Other adverse effects include mental disturbances, incoordination, optic neuritis and convulsions. 

Vitamin B Three substances are classed under the term pyridoxine or adermine pyridoxol, pyridoxal and pyridoxamine. Pyridoxine was isolated by various study groups in 1938. Its structure was described by Folkers and Kuhn in 1939. Pyridoxal and pyridoxamine were discovered by Snell in 1942. Pyridoxal phosphate and pyridoxamine phosphate are biologically active substances. Intestinal absorption of Bg is dose-dependent and not limited. In alcoholism, a deficiency of vitamin Bg is encountered in 20—30% of cases, whereas the respective percentage is 50—70% in alcoholic cirrhosis. Vitamin Bg is an important coenzyme for transaminases, which transfer amino groups from amino adds to keto acids. In this way, biochemical pathways between the dtiic acid cycle and carbohydrate and amino acid metabolisms are created. (104)... 

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