Importance of experimental conditions in evaluating the malonyl-CoA sensitivity of liver carnitine acyltransferase. Studies with fed and starved rats.
Importance of experimental conditions in evaluating the malonyl-CoA sensitivity of liver carnitine acyltransferase. Studies with fed and starved rats.
复制标题
实验条件在评估肝脏肉毒碱酰基转移酶丙二酰辅酶A敏感性中的重要性。
DOI：
10.1042/bj2000217
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Foster,DW
中科院分区：
文献类型：
--
作者：
McGarry,JD;Foster,DW
实验再次证实了丙二酰辅酶A对大鼠肝线粒体肉碱酰基转移酶I和脂肪酸氧化的强大抑制作用（Ki 1.5 microM）。敏感性随饥饿而降低（饥饿 18 小时后 Ki 为 3.0 µM，42 小时后为 5.0 µM）。库克、奥托和康奈尔的观察[生物化学。 J. (1980) 192, 955--958] 和 Ontko & Johns [Biochem。 J.(1980) 192, 959--962]对丙二酰辅酶A在肝脂肪酸氧化和生酮调节中的生理作用提出了质疑。引用的研究中获得的高 Ki 值被证明是由于孵化条件导致底物耗尽、丙二酰辅酶 A 破坏或产生过高浓度的未结合酰基辅酶 A（这抵消了丙二酰辅酶 A 对肉碱酰基转移酶 I 的竞争性抑制）。目前的结果与丙二酰辅酶A作为大鼠肝脏脂肪酸合成和氧化的主要调节剂的假设作用完全一致。
The experiments reconfirm the powerful inhibitory effect of malonyl-CoA on carnitine acyltransferase I and fatty acid oxidation in rat liver mitochondria (Ki 1.5 microM). Sensitivity decreased with starvation (Ki after 18 h starvation 3.0 microM, and after 42 h 5.0 microM). Observations by Cook, Otto & Cornell [Biochem. J. (1980) 192, 955--958] and Ontko & Johns [Biochem. J. (1980) 192, 959--962] have cast doubt on the physiological role of malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. The high Ki values obtained in the cited studies are shown to be due to incubation conditions that cause substrate depletion, destruction of malonyl-CoA or generation of excessively high concentrations of unbound acyl-CoA (which offsets the competitive inhibition of malonyl-CoA towards carnitine acyltransferase I). The present results are entirely consistent with the postulated role of malonyl-CoA as the primary regulatory of fatty acid synthesis and oxidation in rat liver.