Growth-promoting activity of pyrazinoic acid, a putative active compound of antituberculosis drug pyrazinamide, in niacin-deficient rats through the inhibition of ACMSD activity.
We have recently reported that the antituberculosis drug, pyrazinamide (PZA), caused a significant increase in the conversion ratio of tryptophan to niacin in rats. In the present work, we investigated whether or not pyrazinoic acid (POA), a putative metabolite of PZA, increased the conversion ratio of tryptophan to niacin. Weaning rats were fed with a niacin-free and tryptophan-limited diet (negative control diet), or with the negative control diet supplemented with 0.003% nicotinic acid (positive control diet) or 1% POA (test diet) for 27 days. The growth rate was almost same between the groups fed on the positive control diet and the test diet. Dietary POA significantly increased the conversion ratio of tryptophan to niacin. Although POA did not directly inhibit the activity of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD), the rate-limiting enzyme in the tryptophan-niacin pathway, liver ACMSD activity was only not detected in the test diet group. These results suggest that a derivative of POA metabolized by rats inhibited the ACMSD activity.
Fukuwatari
Tsutomu
T
Department of Life Style Studies, School of Human Cultures, The University of Shiga Prefecture, Hikone, Japan. fukkie@shc.usp.ac.jp
Sugimoto
Etsuro
E
Shibata
Katsumi
K
D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D004032:Diet; D004435:Eating / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007736:Kynurenic Acid / Q000652:urine; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009243:NAD / Q000378:metabolism; D009525:Niacin / Q000172:deficiency*; D011718:Pyrazinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014364:Tryptophan / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects; D014977:Xanthurenates / Q000652:urine
D000995:Antitubercular Agents; D014977:Xanthurenates; D009243:NAD; D009525:Niacin; D011718:Pyrazinamide; C005296:pyrazinoic acid; C028330:xanthurenic acid; D014364:Tryptophan; D002262:Carboxy-Lyases; C024396:aminocarboxymuconate-semialdehyde decarboxylase; D007736:Kynurenic Acid