Derrick J P, Ramsay R R
Department of Biochemistry, University of Cambridge, U.K.
Biochem J. 1989 Sep 15;262(3):801-6. doi: 10.1042/bj2620801.
Inhibition of the overt mitochondrial carnitine palmitoyltransferase by malonyl-CoA is important in the regulation of fatty acid oxidation. In the past, the contribution of peroxisomal carnitine acyltransferase activity to the generation of medium- and long-chain acylcarnitines in the cytoplasm has been ignored. On the basis of marker enzyme levels, we now estimate that peroxisomal palmitoyltransferase activity constitutes about 20% of the peroxisomal plus overt-mitochondrial pool in fed rat liver. When assayed in situ, both the palmitoyltransferase and decanoyltransferase activities of gradient-purified peroxisomes are sensitive to malonyl-CoA, with up to 90% inhibition reached at less than 10 microM-malonyl-CoA. Very similar results were obtained with intact gradient-purified mitochondria from the same livers. In addition, the acyl-CoA substrate chain-length specificity was identical in both the peroxisomes and the mitochondria, with a decanoyltransferase/palmitoyltransferase ratio of 2. Thus the overt carnitine acyltransferase activities in peroxisomes and mitochondria have the same properties. Further, the malonyl-CoA sensitivity of the peroxisomal activity is lost on solubilization, as has been observed for the overt mitochondrial enzyme. It is suggested that malonyl-CoA inhibition of the peroxisomal enzyme as well as of the mitochondrial enzyme is important for the regulation of mitochondrial fatty acid oxidation.
丙二酰辅酶A对明显的线粒体肉碱棕榈酰转移酶的抑制作用在脂肪酸氧化调节中很重要。过去，过氧化物酶体肉碱酰基转移酶活性对细胞质中中链和长链酰基肉碱生成的贡献一直被忽视。根据标记酶水平，我们现在估计，在喂食的大鼠肝脏中，过氧化物酶体棕榈酰转移酶活性占过氧化物酶体加明显线粒体池的约20%。当原位测定时，梯度纯化的过氧化物酶体的棕榈酰转移酶和癸酰转移酶活性均对丙二酰辅酶A敏感，在丙二酰辅酶A浓度低于10微摩尔时，抑制率可达90%。从相同肝脏中获得的完整梯度纯化线粒体也得到了非常相似的结果。此外，过氧化物酶体和线粒体中酰基辅酶A底物链长特异性相同，癸酰转移酶/棕榈酰转移酶的比率为2。因此，过氧化物酶体和线粒体中明显的肉碱酰基转移酶活性具有相同的特性。此外，正如在明显的线粒体酶中观察到的那样，过氧化物酶体活性对丙二酰辅酶A的敏感性在溶解后丧失。有人提出，丙二酰辅酶A对过氧化物酶体酶和线粒体酶的抑制作用对线粒体脂肪酸氧化的调节很重要。
