Yamada R, Wakabayashi Y, Iwashima A
Acta Vitaminol Enzymol. 1984;6(1):29-39.
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.
以100毫克/千克体重的剂量给小鼠或大鼠腹腔注射抗结核药物异烟肼（IN），可导致肝脏胞质天冬氨酸氨基转移酶（AAT）受到显著且快速的抑制；其他抗维生素B6化合物的抑制作用则不太明显；IN对其他组织中的AAT以及肝脏中的其他氨基转移酶的抑制效果较差。肝脏胞质AAT的抑制在体内显然是不可逆的；尽管用磷酸吡哆醛或5'-脱氧吡哆醛处理可缓慢恢复其全部活性，但在体外通过凝胶过滤和透析去除过量的IN后，其活性仅略有恢复。体外处理抑制该酶的尝试表明，IN本身并非有效抑制剂，而用IN处理过的小鼠的肝脏提取物中含有某种强抑制性物质。此外，提取物中仅含有痕量的IN。这些结果表明，IN被代谢为某种对小鼠肝脏胞质AAT具有显著抑制作用的其他形式，且该代谢产物以不易解离的方式与酶的辅酶部分结合。
