遗传性酪氨酸血症酶缺乏的生化研究。

Biochemical studies on the enzymatic deficiencies in hereditary tyrosinemia.

作者信息

Berger R, van Faassen H, Smith G P

出版信息

Clin Chim Acta. 1983 Oct 31;134(1-2):129-41. doi: 10.1016/0009-8981(83)90191-2.

Abstract

Experiments are described on the effects of succinylacetone and fumarylacetoacetate on delta-aminolevulinic acid dehydratase, methionine adenosyltransferase and p-OH-phenylpyruvate dioxygenase. delta-Aminolevulinic acid dehydratase from human erythrocytes is inhibited non-competitively by succinylacetone (Ki 0.03 mumol/l) and by fumarylacetoacetate (Ki 0.06 mumol/l). The inhibition by succinylacetone is not prevented by dithiothreitol, but the inhibition by fumarylacetoacetate is not observed if dithiothreitol is present. Methionine adenosyltransferase, partially purified from rabbit liver, is not inhibited by succinylacetone but is inhibited by fumarylacetoacetate: 69% inhibition is observed at 1 mmol/l. Human liver p-OH-phenylpyruvate dioxygenase is not inhibited by succinylacetone or fumarylacetoacetate. It is concluded that secondary enzyme deficiencies observed in hereditary tyrosinemia (delta-aminolevulinic acid dehydratase, methionine adenosyl transferase) are the result of inhibition by succinylacetone and fumarylacetoacetate, accumulating as a result of a primary deficiency of fumarylacetoacetase.

摘要

本文描述了琥珀酰丙酮和富马酰乙酰乙酸对δ-氨基乙酰丙酸脱水酶、甲硫氨酸腺苷转移酶和对羟基苯丙酮酸双加氧酶的影响。人红细胞中的δ-氨基乙酰丙酸脱水酶受到琥珀酰丙酮（Ki 0.03 μmol/L）和富马酰乙酰乙酸（Ki 0.06 μmol/L）的非竞争性抑制。二硫苏糖醇不能阻止琥珀酰丙酮的抑制作用，但如果存在二硫苏糖醇，则不会观察到富马酰乙酰乙酸的抑制作用。从兔肝中部分纯化的甲硫氨酸腺苷转移酶不受琥珀酰丙酮抑制，但受富马酰乙酰乙酸抑制：在1 mmol/L时观察到69%的抑制率。人肝对羟基苯丙酮酸双加氧酶不受琥珀酰丙酮或富马酰乙酰乙酸抑制。得出的结论是，遗传性酪氨酸血症中观察到的继发性酶缺陷（δ-氨基乙酰丙酸脱水酶、甲硫氨酸腺苷转移酶）是由于富马酰乙酰乙酸酶原发性缺乏而积累的琥珀酰丙酮和富马酰乙酰乙酸抑制的结果。