Pyridoxine vitamin structure

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. 

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

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... 

A study of the formulas of coenzyme and prosthetic groups shows that many contain structures derived from the vitamins (see Chapter 30). Thus, the nicotinamide portion of NAD and NADP derives from the vitamin niacin, whereas the P-5 -P prosthetic group of the aminotransferases is a derivative of pyridoxine, vitamin Bg. Other derivatives of the B-group vitamins participate in enzymatic reactions. 

Transamination reactions require the coenzyme pyridoxal-5 -phosphate (PLP), which is derived from pyridoxine (vitamin B6). PLP is also required in numerous other reactions of amino acids. Examples include racemizations, decarboxylations, and several side chain modifications. (Racemizations are reactions in which mixtures of l- and D-amino acids are formed.) The structures of the vitamin and its coenzyme form are illustrated in Figure 14.2. 

The structure of pyridoxal phosphate, the coenzyme required for all transamination reactions, and pyridoxine, vitamin Bg, the vitamin from which it is derived. 

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. 

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. 

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). 

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 ]. 

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)... 

Although the water-soluble vitamins are structurally diverse, they are put in a general class to distinguish them from the lipid-soluble vitamins. This cla.ss includes the B-complex vitamins and ascorbic acid (vitamin C). The term B-complex vitamins usually refers to thiamine, riboflavin, pyridoxine. nicotinic acid, pantothenic acid, hiotin. cyanocobalamin. and folic acid. Dietary deficiencies of any of the B vitamins commonly are complicated by deftciencies of another mem-ber(s) of the group,. so treatment with B-complex preparations is usually indicated. 

Most vitamins function either as a hormone/ chemical messenger (cholecalciferol), structural component in some metabolic process (pantothenic acid), or a coenzyme (phytonadi-one, thiamine, riboflavin, niacin, pyridoxine, biotin, folic acid, cyanocobalamin). At least one vitamin has more than one biochemical role. Vitamin A as an aldehyde (retinal) is a structural component of the visual pigment rhodopsin and, in its acid form (retinoic acid), is a regulator of cell differentiation. The precise biochemical functions of ascorbic acid and a-tocopherol still are not well defined. 

The first component of vitamin B6, pyridoxine, was first synthesized, also in 1938, by the Austrian-German chemist Richard Kuhn (1900-1967). Its chemical structure was determined a year later by American chemists Karl August Folkers (1906-1997) and S. A. Harris (dates not available) at the... 

The fact is, there have been no systematic studies of the effects of nutrients like vitamins on the structure or rate of wool or hair growth. However, there are some indications that in dietary insufficiencies, supplements of folic acid (a B complex vitamin) or pyridoxine (a B complex vitamin. Be) could be helpful to hair growth. The logic behind these indications is that these vitamins play a role in cysteine metabolism [106]. On the other hand, panthenol, the precursor to pantothenic acid (another B complex vitamin) has never been demonstrated in any published scientific study to affect the nutrition or growth of hair. In a review on nutrition and hair, Flesch [107] reported, There is no objective evidence available to support the assumption that pantothenic acid has a biochemical role in the production of hair. ... 

The pyridine system is found in natural products, for example, in nicotine (1) from tobacco, ricinine (2) fi-om castor bean, vitamins such as pyridoxine or vitamin Be (3) and vitamin P (4), and alkaloids such as coniine and piperine. Free pyridine is present in tobacco smoke. Diploclidine (5) and njdcinadine A (6) are two examples of recently isolated and structurally diverse natural products containing the pyridine core. ... 

---