"In vivo" inhibition of murine liver aspartate aminotransferase by isoniazid.
Intraperitoneal administration of isoniazid (IN), an antituberculous agent, to mice or rats at a dose of 100 mg/kg body weight resulted in remarkable and rapid inhibition of liver cytosolic aspartate aminotransferase (AAT); inhibition was less marked with other antivitamin B6 compounds; AATs in other tissues and other aminotransferases in liver were less effectively inhibited by IN. The inhibition of liver cytosolic AAT was apparently irreversible in vivo; it was reversed only a little by gel filtration and dialysis to remove excess IN in vitro, although treatment with pyridoxal phosphate or 5'-deoxypyridoxal slowly restored the full activity. Attempts to inhibit the enzyme by in vitro treatments showed that IN itself was not an effective inhibitor, while the liver extracts from IN treated mice contained some strongly inhibitory substance. In addition, the extracts were shown to contain only trace amounts of IN. These results suggest that IN is metabolized to some other form which is markedly inhibitory to murine liver cytosolic AAT, and the metabolite binds to the coenzyme moiety of enzyme in a manner not readily dissociable.
D000818:Animals; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors*; D007538:Isoniazid / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D009206:Myocardium / Q000201:enzymology; D011732:Pyridoxal Phosphate / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011732:Pyridoxal Phosphate; D001219:Aspartate Aminotransferases; D007538:Isoniazid