BIOCHEMICAL-STUDIES ON THE ENZYMATIC DEFICIENCIES IN HEREDITARY TYROSINEMIA
BIOCHEMICAL-STUDIES ON THE ENZYMATIC DEFICIENCIES IN HEREDITARY TYROSINEMIA
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DOI：
10.1016/0009-8981(83)90191-2
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发表时间：
1983-01-01
影响因子：
5
通讯作者：
SMITH, GPA
中科院分区：
文献类型：
--
作者：
BERGER, R;VANFAASSEN, H;SMITH, GPA
本文报道了丁二基丙酮和富马酸乙酰乙酸酯对β-氨基酮戊酸脱水酶、蛋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β-氨基乙酰丙酸脱水酶可被琥珀酸丙酮(Ki 0.03µm ol/L)和富马酸乙酰乙酸酯(Ki 0.06µm ol/L)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，但在二硫苏糖醇存在的情况下，延胡索乙酸延胡索乙酯的抑制作用不被观察到。从兔肝中分离纯化的甲硫氨酸腺苷转移酶不受琥珀酸丙酮的抑制，但可被富马酸乙酰乙酸酯抑制，当浓度为1 mmol/L时，抑制率为69%，人肝对羟基苯丙酮酸双加氧酶不受琥珀酸丙酮和富马酸乙酰乙酸酯的抑制。遗传性酪氨酸血症(β-氨基酮戊酸脱水酶、蛋氨酸腺苷转移酶)中观察到的继发性酶缺陷是琥珀酸丙酮和富马酸乙酰乙酸酯抑制的结果，由于富马酸乙酰乙酸酶的原发缺陷而积累。
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 .mu.mol/l) and by fumarylacetoacetate (Ki 0.06 .mu.mol/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. Secondary enzyme deficiences observed in hereditary tyrosinemia (.delta.-aminolevulinic acid dehydratase, methionine adenosyltransferase) are the result of inhibition by succinylacetone and fumarylacetoacetate, accumulating as a result of a primary deficiency of fumarylacetoacetase.