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The effect of drugs on vitamin B6function in the rat

Authors
Journal
Biochemical Pharmacology
0006-2952
Publisher
Elsevier
Publication Date
Volume
29
Issue
22
Identifiers
DOI: 10.1016/0006-2952(80)90452-9
Disciplines
  • Biology
  • Chemistry

Abstract

Abstract Some commonly used drugs were tested for an effect on vitamin B 6 function in Lister Hooded rats. An increase in urinary xanthurenic acid excretion after a tryptophan load was used as an indicator of impaired vitamin B 6 function. dl-Penicillamine, hydrallazine and phenelzine produced increases in xanthurenic acid excretion, and these were reversed by concomitant treatment of the animals with pyridoxine hydrochloride. dl-Penicillamine was the only drug which lowered the liver pyridoxal-5'-phosphate (PLP) content of these rats. dl-Penicillamine did not inhibit kynurenine aminotransferase (KAT) in vitro, whilst hydrallazine and phenelzine both inhibited the enzyme non-competitively with respect to the substrate. Hydrallazine produced mixed inhibition of KAT with respect to PLP; inhibition by phenelzine increased as the PLP concentration increased, indicating that the hydrazone formed between phenelzine and PLP was a more potent inhibitor of KAT than phenelzine itself. Isonicotinic acid hydrazide and its metabolites did not increase the xanthurenic acid excretion of tryptophan-loaded rats, and they were weak inhibitors of tryptophan pyrrolase in vitro. It is suggested that drugs may impair the normal function of vitamin B 6 by reducing tissue PLP levels, either through chemical reaction between drug and PLP or by inhibition of PLP synthesis. Drugs may also inhibit PLP-dependent enzymes without affecting systemic PLP levels.

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