Pyridoxine vitamin pyridoxal

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. 

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

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 usable range for T. pyriformis is from 0.3-300 mug/ml. The organism utilizes pyridoxal, pyridoxamine pyridoxine, and pyridoxal-5-phosphate. Pyridoxamine + pyridoxal yielded the best growth approximately 120 times more pyridoxine is required to yield the same growth as pyridoxamine (Fig. 4). As with nicotinic acid and its amide, when these compounds are added together in the same concentration, the increment of growth is less than the sum of the individual increments. Upon an intramuscular load dose of 100 mg of pyridoxine, peak vitamin Bs levels are reached 2 hours after injection. The curves for 4 normal individuals are illustrated in Fig. 5. 

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. 

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. 

Pyridoxal phosphate Amino groups Pyridoxine (vitamin B6)... 

The six principal B6 vitamers are widely distributed in foods (102,103). They include pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM), and their 5 -phosphate esters, pyridoxine phosphate (PNP), pyridoxal phosphate (PLP), and pyridoxamine phosphate (PMP) (Fig. 5). The predominate B6 vitamer in animal-based foods is PLP, whereas plant products generally contain PN and PM or their phosphorylated forms. Conjugated vitamers in the form of PN-glycosides have also been isolated from plant-based foods. Pyridoxal is readily converted to PM during cooking and food processing. Total vitamin B6 is the sum of the six principal vitamers inclusion of the conjugated forms depends on the extraction procedure. 

Wozenski et al. (60) have reported the metabolism of small doses of vitamin Bg in men. It has been found that responses to pyridoxamine are generally slower than for pyridoxine or pyridoxal, suggesting that pyridoxamine is absorbed more slowly or metabolized differently, or both, than pyridoxal or pyridoxine. A dose of at least 1 mg of Bg is necessary to obtain measurable changes in vitamin Bg metabolism. 

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

Pyridoxine (vitamin Bb, in the form of pyridoxal phosphate) is a cofactor in the formation of dopamine from L-DOPA. It used to be thought that pyridoxine supplements would be helpful to treat Parkinson s disease. The opposite was found vitamin B6 apparently also enhances L-DOPA conversion to dopamine in other areas of the body. This means that less of the administered L-DOPA is available for entry into tlie brain. Therefore, Be treatment presently is contraindicated in Parkinson s disease. 

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... 

Pyridoxal phosphate, the coenzyme of pyridoxine (vitamin B6) plays an important role in these reactions. Amino transferase reactions occur in two stages. 

TLC of vitamin Be compounds, on various layers in different solvents, was studied. The Rf values of pyri-doxine, pyridoxal, pyridoxamine, pyridoxal ethyl acetate, 4-pyridoxic acid, 4-pyridoxic acid lactone, pyridoxine phosphate, pyridoxal phosphate, and pyridoxamine phosphate were 0.62, 0.68, 0.12, 0.54, 0.91, 0.91, 0.95, 0.95, and 0.86, respectively, by TLC on silica gel HF254 with... 

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... 

Uptake and Metabolism. The vitamin Bg family consists of pyridoxine, pyridoxal, pyridoxamine, pyridoxine phosphate, pyridoxal phosphate (PLP), and pyridoxamine phosphate (Fig. 8.33). The commercial form is pyridoxine. Pyridoxal phosphate is the coenzyme form. It and pyridoxamine phosphate are from animal tissues. Pyridoxine is from plant tissues. All phosphorylated forms are hydrolyzed in the intestinal tract by phosphatases before being absorbed passively. Conversion to the phosphorylated forms occurs in the liver. Notice that niacin (NAD) and riboflavin (FMN, FAD) are required for interconversion among the vitamin Bq family. The phosphorylated forms are transported to the cells where needed. The major excretory product is 4-pyr-idoxic acid. 

Vitamin Bg status can be evaluated by direct measurement of plasma pyridoxine or pyridoxal phosphate by microbiological, enzymatic, radioimmunological, or chemical methods. Measurement of urinary xanthurenic acid or other intermediates of the kynurenine pathway (Chapter 17) are used to assess indirectly the adequacy of vitamin Bg for metabolic needs. 

Bi) is converted to thiamine pyrophosphate simply by the addition of pyrophosphate. It is involved in aldehyde group transfer. Niacin (nicotinic acid) is esterified to adenine dinucleotide and its two phosphates to form nicotinamide adenine dinucleotide. Pyridoxine (vitamin B ) is converted to either pyridoxal phosphate or pyridoxamine phosphate before complexing with enzymes. Riboflavin becomes flavin mononucleotide by obtaining one phosphate (riboflavin 5 -phosphate). If it complexes with adenine dinucleotide via a pyrophosphate ester linkage, it becomes flavin adenine dinucleotide. 

Pyridoxal phosphate The coenzyme that is required for transaminase (aminotransferase) reactions, as weU as other enzymes. It is the active form of pyridoxine (vitamin B ). 

VITAMIN B6 (Pyridoxine) As pyridoxal-5-phosphate. Vitamin B6 functions as a coenzyme in amino acid decarboxylases and transaminases. It occurs in meat (liver), fish (salmon), carrot, avocado and other fruits, egg yolk and yeast. Synthetic material is also used. 

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. 

Vitamin B6 includes (a) pyridoxine, (b) pyridoxal, and (c) pyridoxam-ine. (Pyridoxine is found in leafy green vegetables. Pyridoxal and pyri-doxamine are found in animal foods such as fish, poultry, and red meat.) The biologically active form of vitamin B6 is (d) pyridoxal-5 -phosphate. 

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