肉碱棕榈酰转移酶I对丙二酰辅酶A抑制的敏感性是调节新生兔和胎兔肝脏脂肪酸氧化的重要位点的证据。围产期发育及胰腺激素对培养的兔肝细胞的影响。
Evidence that the sensitivity of carnitine palmitoyltransferase I to inhibition by malonyl-CoA is an important site of regulation of hepatic fatty acid oxidation in the fetal and newborn rabbit. Perinatal development and effects of pancreatic hormones in cultured rabbit hepatocytes.
作者信息
Prip-Buus C, Pegorier J P, Duee P H, Kohl C, Girard J
机构信息
Centre de Recherche sur la Nutrition du CNRS, Meudon-Bellevue, France.
出版信息
Biochem J. 1990 Jul 15;269(2):409-15. doi: 10.1042/bj2690409.
The temporal changes in oleate oxidation, lipogenesis, malonyl-CoA concentration and sensitivity of carnitine palmitoyltransferase I (CPT 1) to malonyl-CoA inhibition were studied in isolated rabbit hepatocytes and mitochondria as a function of time after birth of the animal or time in culture after exposure to glucagon, cyclic AMP or insulin. (1) Oleate oxidation was very low during the first 6 h after birth, whereas lipogenesis rate and malonyl-CoA concentration decreased rapidly during this period to reach levels as low as those found in 24-h-old newborns that show active oleate oxidation. (2) The changes in the activity of CPT I and the IC50 (concn. causing 50% inhibition) for malonyl-CoA paralleled those of oleate oxidation. (3) In cultured fetal hepatocytes, the addition of glucagon or cyclic AMP reproduced the changes that occur spontaneously after birth. A 12 h exposure to glucagon or cyclic AMP was sufficient to inhibit lipogenesis totally and to cause a decrease in malonyl-CoA concentration, but a 24 h exposure was required to induce oleate oxidation. (4) The induction of oleate oxidation by glucagon or cyclic AMP is triggered by the fall in the malonyl-CoA sensitivity of CPT I. (5) In cultured hepatocytes from 24 h-old newborns, the addition of insulin inhibits no more than 30% of the high oleate oxidation, whereas it stimulates lipogenesis and increases malonyl-CoA concentration by 4-fold more than in fetal cells (no oleate oxidation). This poor effect of insulin on oleate oxidation seems to be due to the inability of the hormone to increase the sensitivity of CPT I sufficiently. Altogether, these results suggest that the malonyl-CoA sensitivity of CPT I is the major site of regulation during the induction of fatty acid oxidation in the fetal rabbit liver.
在新生兔出生后的不同时间或细胞培养一定时间后，分别用胰高血糖素、环磷酸腺苷（cAMP）或胰岛素处理，研究了离体兔肝细胞和线粒体中油酸氧化、脂肪生成、丙二酰辅酶A浓度以及肉碱棕榈酰转移酶I（CPT 1）对丙二酰辅酶A抑制作用的敏感性随时间的变化。（1）出生后的前6小时内，油酸氧化水平很低，而在此期间脂肪生成速率和丙二酰辅酶A浓度迅速下降，降至与24小时龄且有活跃油酸氧化的新生兔相当的低水平。（2）CPT I的活性变化以及丙二酰辅酶A的半数抑制浓度（IC50）变化与油酸氧化的变化趋势一致。（3）在培养的胎肝细胞中，添加胰高血糖素或cAMP可重现出生后自发发生的变化。暴露于胰高血糖素或cAMP 12小时足以完全抑制脂肪生成并导致丙二酰辅酶A浓度降低，但诱导油酸氧化则需要暴露24小时。（4）胰高血糖素或cAMP诱导油酸氧化是由CPT I对丙二酰辅酶A敏感性的降低引发的。（5）在24小时龄新生兔的培养肝细胞中，添加胰岛素对高油酸氧化的抑制作用不超过30%，而它刺激脂肪生成并使丙二酰辅酶A浓度比胎肝细胞（无油酸氧化）增加4倍。胰岛素对油酸氧化的这种微弱作用似乎是由于该激素无法充分提高CPT I的敏感性。总之，这些结果表明，CPT I对丙二酰辅酶A的敏感性是胎兔肝脏脂肪酸氧化诱导过程中的主要调节位点。
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