Melde K, Buettner H, Boschert W, Wolf H P, Ghisla S
University of Konstanz, Federal Republic of Germany.
Biochem J. 1989 May 1;259(3):921-4. doi: 10.1042/bj2590921.
The effects of methylenecyclopropylglycine (MCPG), the lower homologue of hypoglycin A, on starved rats are described. Upon oral ingestion of MCPG (43 mg/kg), a 50% decrease in blood glucose compared with controls was observed after 4 h. The plasma concentrations of lactate and non-esterified fatty acids were substantially increased during this period. The activity of general acyl-CoA dehydrogenase from isolated rat liver mitochondria was not significantly changed. By contrast, the activity of 2-methyl-(branched-chain)-acyl-CoA dehydrogenase decreased by over 80%. The enzyme activity of enoyl-CoA hydratase (crotonase) from pig kidneys decreased by 80% on incubation with the hypothetically toxic metabolite of MCPG, methylenecyclopropylformyl-CoA. These results suggest that the inhibition spectrum of MCPG is quite different from that of hypoglycin A and that similar physiological effects might result from inhibition of different enzymes of beta-oxidation, e.g. hypoglycaemia and lacticacidemia. Accumulation of medium-chain acyl-CoA thioesters is probably at the origin of disturbances in pyruvate metabolism.
本文描述了低血糖素A的低级同系物亚甲基环丙基甘氨酸（MCPG）对饥饿大鼠的影响。口服MCPG（43毫克/千克）后，4小时时观察到血糖水平相较于对照组降低了50%。在此期间，血浆中乳酸和非酯化脂肪酸的浓度大幅升高。分离出的大鼠肝脏线粒体中一般酰基辅酶A脱氢酶的活性没有显著变化。相比之下，2-甲基-（支链）-酰基辅酶A脱氢酶的活性下降了80%以上。猪肾中烯酰辅酶A水合酶（巴豆酸酶）与MCPG的假定毒性代谢产物亚甲基环丙基甲酰辅酶A一起孵育时，酶活性下降了80%。这些结果表明，MCPG的抑制谱与低血糖素A有很大不同，并且β-氧化的不同酶受到抑制可能会导致类似的生理效应，如低血糖症和乳酸血症。中链酰基辅酶A硫酯的积累可能是丙酮酸代谢紊乱的根源。
