Kotal P, Klepácek I, Jirsa M, Kordac V
Sb Lek. 1989 Jun;91(6):161-8.
Increased activity of haem synthesis key enzyme is a common phenomenon in hepatic porphyrias. Synthase activity of delta-aminolevulinic acid is extensively increased in acute hepatic porphyrias or it can be by means of feedback moderately secondarily increased in their chronic forms. Isonicotinic acid hydrazide (INH) is a competitive inhibitor of delta-aminolevulinic acid synthase as it combines with enzyme co-factor, pyridoxalphosphate (PDX) to form hydrazone. The INH porphyrinstatic effects were verified by testing two experimental models. The yeast model exhibited 5-fold inhibition at 10 mM INH concentration in medium. The chicken germ model after a 10 microM INH dose exhibited 82% inhibition. This inhibition can be eliminated by PDX administration to reach the original porphyrin synthesis at equimolar INH and PDX concentrations. Histological study of transversal chicken liver sections proved that 1 microM INH administration does not result in disturbance of chicken hepatocyte integration. The suggested preparation has the advantage of being commonly manufactured and approved to be used in human medicine.
血红素合成关键酶活性增加是肝性卟啉病的常见现象。在急性肝性卟啉病中，δ-氨基-γ-酮戊酸合酶活性广泛增加，或者在其慢性形式中可通过反馈作用适度继发增加。异烟肼（INH）是δ-氨基-γ-酮戊酸合酶的竞争性抑制剂，因为它与酶辅因子磷酸吡哆醛（PDX）结合形成腙。通过测试两种实验模型验证了INH的卟啉抑制作用。酵母模型在培养基中10 mM INH浓度下表现出5倍的抑制作用。10 μM INH剂量后的鸡胚模型表现出82%的抑制作用。通过给予PDX可以消除这种抑制作用，在等摩尔的INH和PDX浓度下达到原始的卟啉合成。横向鸡肝切片的组织学研究证明，给予1 μM INH不会导致鸡肝细胞整合紊乱。所建议的制剂具有通常生产且已批准用于人类医学的优点。
