In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase.
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Moriwaki Y, Yamamoto T, Nasako Y, Takahashi S, Suda M, Hiroishi K, Hada T, Higashino K
In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase.
Biochem Pharmacol. 1993 Sep 14;46(6):975-81.
- PubMed ID
- 8216357 [ View in PubMed]
- Abstract
Aldehyde oxidase was purified about 120-fold from rat liver cytosol by sequential column chromatography using diethylaminoethyl (DEAE) cellulose, Benzamidine-Sepharose 6B and gel filtration. The purified enzyme was shown as a single band with M(r) of 2.7 x 10(5) on polyacrylamide gel electrophoresis (PAGE) and M(r) of 1.35 x 10(5) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Using this purified enzyme, in vitro conversion of allopurinol, pyrazinamide and pyrazinoic acid was investigated. Allopurinol and pyrazinamide were oxidized to oxypurinol and 5-hydroxy-pyrazinamide, respectively, while pyrazinoic acid, the microsomal deamidation product of pyrazinamide, was not oxidized to 5-hydroxypyrazinoic acid. The apparent Km value of the enzyme for pyrazinamide was 160 microM and that for allopurinol was 1.1 mM. On PAGE, allopurinol- or pyrazinamide-stained band was coincident with Coomassie Brilliant Blue R 250-stained band, respectively. These results suggest that aldehyde oxidase may play a role in the oxidation of allopurinol to oxypurinol and that of pyrazinamide to 5-hydroxypyrazinamide with xanthine dehydrogenase which can oxidize both allopurinol and pyrazinamide in vivo. The aldehyde oxidase may also play a major role in the oxidation of allopurinol and pyrazinamide in the subgroup of xanthinuria patients (xanthine oxidase deficiency) who can oxidize both allopurinol and pyrazinamide.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Allopurinol Aldehyde oxidase Protein Humans UnknownSubstrateDetails Pyrazinamide Aldehyde oxidase Protein Humans UnknownSubstrateDetails Pyrazinamide Xanthine dehydrogenase/oxidase Protein Humans UnknownSubstrateDetails