Boquist L, Ericsson I
FEBS Lett. 1984 Dec 10;178(2):245-8. doi: 10.1016/0014-5793(84)80609-2.
Considerable variations were found in the in vitro effect of alloxan on mouse liver enzymes associated with the citric acid cycle. The following approximative alloxan concentrations induced 50% inhibition of enzyme activity: 10(-6)M for aconitase, 10(-4)M for NAD-linked isocitrate dehydrogenase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinyl-CoA synthetase and fumarase, and 10(-3)M for citrate synthase and NADP-linked isocitrate dehydrogenase. Pyruvate dehydrogenase, succinate dehydrogenase and malate dehydrogenase were not inhibited by 10(-3)M alloxan. The inhibition of aconitase was competitive both when using mouse liver and purified porcine heart enzyme. The Ki values for the purified enzyme in the presence of 5 microM alloxan were 0.22 microM with citrate, 4.0 microM with cis-aconitate and 0.62 microM with isocitrate as substrate. The high sensitivity of aconitase for inhibition by alloxan probably plays a prominent role for the toxic effects of alloxan.
发现四氧嘧啶对与柠檬酸循环相关的小鼠肝脏酶的体外作用存在相当大的差异。以下近似的四氧嘧啶浓度可诱导50%的酶活性抑制：乌头酸酶为10(-6)M，NAD连接的异柠檬酸脱氢酶、谷氨酸脱氢酶、α-酮戊二酸脱氢酶、琥珀酰辅酶A合成酶和延胡索酸酶为10(-4)M，柠檬酸合酶和NADP连接的异柠檬酸脱氢酶为10(-3)M。丙酮酸脱氢酶、琥珀酸脱氢酶和苹果酸脱氢酶不受10(-3)M四氧嘧啶的抑制。无论是使用小鼠肝脏还是纯化的猪心脏酶，乌头酸酶的抑制作用都是竞争性的。在5 microM四氧嘧啶存在下，以柠檬酸为底物时纯化酶的Ki值为0.22 microM，以顺乌头酸为底物时为4.0 microM，以异柠檬酸为底物时为0.62 microM。乌头酸酶对四氧嘧啶抑制的高敏感性可能在四氧嘧啶的毒性作用中起重要作用。
