Lysiak W, Lilly K, DiLisa F, Toth P P, Bieber L L
Department of Biochemistry, Michigan State University, East Lansing 48824.
J Biol Chem. 1988 Jan 25;263(3):1151-6.
The steady state levels of mitochondrial acyl-CoAs produced during the oxidation of pyruvate, alpha-ketoisovalerate, alpha-ketoisocaproate, and octanoate during state 3 and state 4 respiration by rat heart and liver mitochondria were determined. Addition of carnitine lowered the amounts of individual short-chain acyl-CoAs and increased CoASH in a manner that was both tissue- and substrate-dependent. The largest effects were on acetyl-CoA derived from pyruvate in heart mitochondria using either state 3 or state 4 oxidative conditions. Carnitine greatly reduced the amounts of propionyl-CoA derived from alpha-ketoisovalerate, while smaller effects were obtained on the branched-chain acyl-CoA levels, consistent with the latter acyl moieties being poorer substrates for carnitine acetyltransferase and also poorer substrates for the carnitine/acylcarnitine translocase. The levels of acetyl-CoA in heart and liver mitochondria oxidizing octanoate during state 3 respiration were lower than those obtained with pyruvate. The rate of acetylcarnitine efflux from heart mitochondria during state 3 (with pyruvate or octanoate as substrate, in the presence or absence of malate with 0.2 mM carnitine) shows a linear response to the acetyl-CoA/CoASH ratio generated in the absence of carnitine. This relationship is different for liver mitochondria. These data demonstrate that carnitine can modulate the aliphatic short-chain acyl-CoA/CoA ratio in heart and liver mitochondria and indicate that the degree of modulation varies with the aliphatic acyl moiety.
测定了大鼠心脏和肝脏线粒体在状态3和状态4呼吸过程中，丙酮酸、α-酮异戊酸、α-酮异己酸和辛酸氧化过程中产生的线粒体酰基辅酶A的稳态水平。添加肉碱降低了各个短链酰基辅酶A的量，并以组织和底物依赖性的方式增加了辅酶A。最大的影响是在使用状态3或状态4氧化条件的心脏线粒体中，对源自丙酮酸的乙酰辅酶A的影响。肉碱大大降低了源自α-酮异戊酸的丙酰辅酶A的量，而对支链酰基辅酶A水平的影响较小，这与后一种酰基部分是肉碱乙酰转移酶的较差底物以及肉碱/酰基肉碱转位酶的较差底物一致。在状态3呼吸过程中，氧化辛酸的心脏和肝脏线粒体中的乙酰辅酶A水平低于丙酮酸氧化时的水平。在状态3（以丙酮酸或辛酸为底物，在有或没有苹果酸和0.2 mM肉碱的情况下），心脏线粒体中乙酰肉碱的流出速率对在没有肉碱的情况下产生的乙酰辅酶A/辅酶A比率呈线性响应。肝脏线粒体的这种关系不同。这些数据表明，肉碱可以调节心脏和肝脏线粒体中脂肪族短链酰基辅酶A/辅酶A的比率，并表明调节程度随脂肪族酰基部分而变化。
