In vivo inhibition of kynurenine aminotransferase activity by isonicotinic acid hydrazide in rats.
It is known that the anti-tuberculosis drug, isonicotinic acid hydrazide (INH), causes pellagra, a niacin deficiency syndrome, and peripheral neuritis in humans. We investigated the effects of INH on the metabolism of tryptophan to niacin in rats fed on a niacin-free diet. The activity of kynurenine aminotransferase was significantly inhibited by feeding a diet containing INH and by an injection of INH, and the urinary excretion of xanthurenic acid, the side-reaction product of the conversion pathway of tryptophan to niacin, was below the limit of detection. The inhibition of kynurenine aminotransferase and the resulting decreased formation of xanthurenic acid generally mean a higher conversion ratio of tryptophan to niacin. However, the conversion ratio was no different between the control and INH groups.
Shibata
K
K
Department of Human Health Science, Faculty of Human Sciences, Osaka International University for Women, Japan.
Marugami
M
M
Kondo
T
T
D000818:Animals; D000995:Antitubercular Agents / Q000633:toxicity*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000633:toxicity; D007538:Isoniazid / Q000633:toxicity*; D008190:Lyases; D008297:Male; D009525:Niacin / Q000172:deficiency / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000637:Transaminases / Q000037:antagonists & inhibitors* / Q000652:urine; D014364:Tryptophan / Q000378:metabolism
D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D011773:Pyruvates; D009525:Niacin; D014364:Tryptophan; D000637:Transaminases; C427605:glutamine - phenylpyruvate transaminase; C021481:kynurenine-oxoglutarate transaminase; D008190:Lyases; D007538:Isoniazid