Pyridoxal kinase

ALCOHOL DEHYDROGENASE Pyridine nucleotide transhydrogenase, NAD(Pr TRANSHYDROGENASE PYRIDOXAL 4-DEHYDROGENASE PYRIDOXAL KINASE... 

THREONINE DEHYDRATASE TRYPTOPHANASE TYROSINE AMINOTRANSFERASE Pyridoxal S -phosphate, synthesis of, PYRIDOXAL KINASE... 

Isonicotinyl hydrazide (INH), one of the most effective drugs against tuberculosis, is inhibitory to pyridoxal kinase, the enzyme that converts pyridoxal to PLP.C Apparently, the drug reacts with pyridoxal to form a hydrazone which blocks the enzyme. Pyridoxal kinase is not the primary target of INH in mycobacteria. However, patients on long-term isonicotinyl hydrazide therapy sometimes suffer symptoms of vitamin B6 deficiency. ... 

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. 

TIQ 135 was reinvestigated by Kametani et al. (253). Pyridoamine, but not pyridoxal, prevented the accumulation of ketonic metabolites of aromatic amino acids by eliminating them as Schiff bases (254). Isoquinolines obtained from pyridoxal and dopamine, such as TIQ 135, did not inhibit the enzyme pyridoxal kinase (255). 

Figure 9.1. Interconversion of the vitamin Be vitamers. Pyridoxal kinase, EC 2.7.1.38 pyridoxine oxidase, EC 1.1.1.65 pyridoxamine phosphate oxidase, EC 1.4.3.5 and pyridoxal oxidase, EC 1.1.3.12. Relative molecular masses (Mr) pyridoxine, 168.3 (hydrochloride, 205.6) pyridoxal, 167.2 pyridoxamine, 168.3 (dihydrochloride, 241.1) pyridoxal phosphate, 247.1 pyridoxamine phosphate, 248.2 and 4-pyridoxlc acid, 183.2.

Gregory JF 3rd (1980a) Effects of epsilon-pyridoxyllysine and related compounds onliver and brain pyridoxal kinase and liver pyridoxamine (pyridoxine) 5 -phosphate oxidase. Journal of Biological Chemistry 255, 2355-9. 

Pyridoxal, pyridoxamine and pyfidoxine are collectively known as vitamin-B6. All three compounds are efficiently converted to the biologically active form of vitamin-B6, pyridoxal phosphate. The ATP requiring enzyme, pyridoxal kinase, catalyzes this conversion. 

In healthy volunteers, theophylline reduced circulating pyridoxal phosphate (vitamin B6) concentrations, presumably by noncompetitive inhibition of pyridoxal kinase. Theophylline concentrations of approximately 10 gg/ml produced only partial inhibition, plasma pyridoxal kinase and pyridoxal concentrations being unaffected. The authors speculated that with theophylline overdose and greater inhibition, vitamin B6 deficiency might contribute to seizures (SEDA-14, 2). 

Vitamin deficiency can result from treatment with certain drags. Thus, destruction of intestinal microorganisms by antibiotic therapy can produce symptoms of vitamin K deficiency. Isoniazid, used to treat tuberculosis, is a competitive inhibitor of pyridoxal kinase, which is needed to produce pyridoxal phosphate. Isoniazid can produce symptoms of pyridoxine deficiency. To prevent this, pyridoxine is often incorporated into isoniazid tablets. Methotrexate and related folate antagonists act by competitively inhibiting dihydrofolate reductase (Chapter 27). 

Metabolism of pyridoxine-related compounds in mammals. Enzymes 1, pyridoxal kinase (present in all mammalian tissues) 2, nonspecific (probably alkaline) phosphatases 3, pyridoxine oxidase (cofactor is FMN O2 is required subject to product inhibition) 4, aldehyde oxidase or aldehyde dehydrogenase 5, aminotransferase,... 

Fig. 1. The metabolic interconversion of various forms of vitamin Bg. Reactions 1, 2 and 3 are catalysed by pyridoxal kinase, reactions 4, S and 6 by various phosphatases, reactions 7, 8 and 10 by pyridoxal-P oxidases, reactions 9 and 11 by certain aminotransferases, and reactions 12 and 13 by various pyridoxal dehydrogenases (taken from ref. 2).

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