Duée P H, Pégorier J P, Quant P A, Herbin C, Kohl C, Girard J
Unité d'Ecologie et de Physiologie du Système Digestif, INRA, 78352 Jouy-en-Josas, France.
Biochem J. 1994 Feb 15;298 ( Pt 1)(Pt 1):207-12. doi: 10.1042/bj2980207.
In newborn-pig hepatocytes, the rate of oleate oxidation is extremely low, despite a very low malonyl-CoA concentration. By contrast, the sensitivity of carnitine palmitoyltransferase (CPT) I to malonyl-CoA inhibition is high, as suggested by the very low concentration of malonyl-CoA required for 50% inhibition of CPT I (IC50). The rates of oleate oxidation and ketogenesis are respectively 70 and 80% lower in mitochondria isolated from newborn-pig liver than from starved-adult-rat liver mitochondria. Using polarographic measurements, we showed that the oxidation of oleoyl-CoA and palmitoyl-L-carnitine is very low when the acetyl-CoA produced is channelled into the hydroxymethylglutaryl-CoA (HMG-CoA) pathway by addition of malonate. In contrast, the oxidation of the same substrates is high when the acetyl-CoA produced is directed towards the citric acid cycle by addition of malate. We demonstrate that the limitation of ketogenesis in newborn-pig liver is due to a very low amount and activity of mitochondrial HMG-CoA synthase as compared with rat liver mitochondria, and suggest that this could promote the accumulation of acetyl-CoA and/or beta-oxidation products that in turn would decrease the overall rate of fatty acid oxidation in newborn- and adult-pig livers.
在新生猪肝细胞中，尽管丙二酰辅酶A浓度极低，但油酸氧化速率却极低。相比之下，肉碱棕榈酰转移酶（CPT）I对丙二酰辅酶A抑制的敏感性较高，这从50%抑制CPT I（IC50）所需的极低丙二酰辅酶A浓度可以看出。从新生猪肝分离的线粒体中，油酸氧化和生酮的速率分别比饥饿成年大鼠肝脏线粒体低70%和80%。通过极谱测量，我们发现当通过添加丙二酸将产生的乙酰辅酶A导入羟甲基戊二酰辅酶A（HMG-CoA）途径时，油酰辅酶A和棕榈酰-L-肉碱的氧化非常低。相反，当通过添加苹果酸将产生的乙酰辅酶A导向柠檬酸循环时，相同底物的氧化很高。我们证明，新生猪肝中生酮的限制是由于与大鼠肝脏线粒体相比，线粒体HMG-CoA合酶的量和活性极低，并表明这可能促进乙酰辅酶A和/或β-氧化产物的积累，进而降低新生猪和成年猪肝中脂肪酸氧化的总体速率。
