Quant P A, Robin D, Robin P, Girard J, Brand M D
Centre de Recherche sur l'Endocrinologie Moléculaire et le Développement, Centre National de la Recherche Scientifique, Meudon-Bellevue, France.
Biochim Biophys Acta. 1993 Feb 13;1156(2):135-43. doi: 10.1016/0304-4165(93)90128-u.
We incubated isolated liver mitochondria with palmitoyl-CoA, 2,4-dinitrophenol and malonate. Under these conditions all the flux of carbon from palmitoyl-CoA was directed towards acetoacetate synthesis. We measured the rate of acetyl-CoA formation from palmitoyl-CoA (by measuring the rate of oxygen consumption) and the rate of acetoacetate production from acetyl-CoA at three different acetyl-CoA/CoA ratios. Using the top-down approach of metabolic control analysis we calculated the control over ketogenesis exerted by (a) the conversion of extramitochondrial palmitoyl-CoA to intramitochondrial acetyl-CoA and by (b) the conversion of acetyl-CoA to acetoacetate (the 'HMG-CoA pathway'). The overall flux control coefficients of the groups of enzymes involved in (a) and (b) over ketogenesis were 0.28 and 0.72, respectively. Our results show that it is possible for significant control to be exerted over ketogenesis by the enzymes of the HMG-CoA pathway.
我们将分离出的肝脏线粒体与棕榈酰辅酶A、2,4-二硝基苯酚和丙二酸一起孵育。在这些条件下，来自棕榈酰辅酶A的所有碳通量都导向乙酰乙酸的合成。我们在三种不同的乙酰辅酶A/辅酶A比率下，测量了从棕榈酰辅酶A生成乙酰辅酶A的速率（通过测量耗氧速率）以及从乙酰辅酶A生成乙酰乙酸的速率。使用代谢控制分析的自上而下方法，我们计算了（a）线粒体外棕榈酰辅酶A转化为线粒体内乙酰辅酶A以及（b）乙酰辅酶A转化为乙酰乙酸（“HMG-CoA途径”）对酮体生成的控制作用。参与（a）和（b）的酶组对酮体生成的总体通量控制系数分别为0.28和0.72。我们的结果表明，HMG-CoA途径的酶有可能对酮体生成施加显著的控制作用。
