乙醛酸对柠檬酸循环的调控。对氧代戊二酸脱氢酶、异柠檬酸脱氢酶和顺乌头酸水合酶的抑制机制。

Control of the citric acid cycle by glyoxylate. The mechanism of inhibition of oxoglutarate dehydrogenase, isocitrate dehydrogenase and aconitate hydratase.

Adinolfi A, Moratti R, Olezza S, Ruffo A

Biochem J. 1969 Sep;114(3):513-8. doi: 10.1042/bj1140513.

Abstract

The effects of glyoxylate on partially purified preparations of aconitate hydratase, isocitrate dehydrogenase and oxoglutarate dehydrogenase were compared with those of oxalomalate and hydroxyoxoglutarate (obtained by condensation of glyoxylate with oxaloacetate and pyruvate respectively). 2. Glyoxylate (1mm) did not affect aconitate hydratase and isocitrate dehydrogenase, whereas oxalomalate (1mm) inhibited the enzyme activities completely. 3. Glyoxylate (0.025mm) inhibited oxoglutarate dehydrogenase irreversibly, whereas the same concentrations of oxalomalate and hydroxyoxoglutarate were ineffective. This inhibitory effect was prevented if oxoglutarate, pyruvate or oxaloacetate was mixed with the enzyme before the glyoxylate. 4. Incubation of oxoglutarate dehydrogenase with radioactive glyoxylate produced radioactive carbon dioxide; radioactivity was also recovered in the portion of the enzyme identified with thiamin pyrophosphate. 5. The behaviour of glyoxylate in producing multiple inhibitions of the citric acid cycle, either by direct interaction with oxoglutarate dehydrogenase, or by means of its condensation compounds which inhibit aconitate hydratase and isocitrate dehydrogenase, is discussed.

摘要

将乙醛酸对乌头酸水合酶、异柠檬酸脱氢酶和氧代戊二酸脱氢酶部分纯化制剂的作用，与草酰苹果酸和羟基氧代戊二酸（分别通过乙醛酸与草酰乙酸和丙酮酸缩合得到）的作用进行了比较。2. 乙醛酸（1 mM）不影响乌头酸水合酶和异柠檬酸脱氢酶，而草酰苹果酸（1 mM）则完全抑制酶活性。3. 乙醛酸（0.025 mM）不可逆地抑制氧代戊二酸脱氢酶，而相同浓度的草酰苹果酸和羟基氧代戊二酸则无作用。如果在加入乙醛酸之前将氧代戊二酸、丙酮酸或草酰乙酸与酶混合，则可防止这种抑制作用。4. 用放射性乙醛酸孵育氧代戊二酸脱氢酶产生放射性二氧化碳；在与硫胺素焦磷酸鉴定的酶部分中也回收了放射性。5. 讨论了乙醛酸通过与氧代戊二酸脱氢酶直接相互作用或通过其抑制乌头酸水合酶和异柠檬酸脱氢酶的缩合化合物对柠檬酸循环产生多重抑制的行为。