Takeyama N, Itoh Y, Kitazawa Y, Tanaka T
Department of Emergency and Critical Care Medicine, Kansai Medical University, Osaka, Japan.
Am J Physiol. 1990 Oct;259(4 Pt 1):E498-505. doi: 10.1152/ajpendo.1990.259.4.E498.
Rat hepatic mitochondrial function, including oxidative phosphorylation, fatty acid oxidative capacity, kinetic parameters of carnitine palmitoyltransferase I (CPT I), and sensitivity of CPT I to malonyl-CoA inhibition were studied in vitro in isolated mitochondria following Escherichia coli lipopolysaccharide (LPS). The hepatic mitochondrial CPT I in LPS-treated rats showed a lower apparent maximum velocity (Vmax) for palmitoyl-CoA and Ki for malonyl-CoA without changes in apparent Km for palmitoyl-CoA. The rate of oxygen consumption or end-product formation of palmitoyl-L-carnitine and octanoate was not altered, but the rate of CPT I-dependent palmitoyl-CoA (plus L-carnitine) oxidation was reduced by LPS, when acetyl-CoA produced via beta-oxidation was directed toward citrate. When acetyl-CoA was directed to acetoacetate, the oxygen consumption rates of palmitoyl-L-carnitine and palmitoyl-CoA (plus L-carnitine) were decreased by LPS, although mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity was not altered. These results indicate that hepatic mitochondria isolated from LPS-treated rats show lower ketogenic and long-chain acyl-CoA oxidative capacity than those of fasted controls, and inhibition of ketogenesis is elicited at a site distal to CPT I in addition to reduction in CPT I activity.
在体外对大肠杆菌脂多糖（LPS）处理后的大鼠分离线粒体进行研究，观察其肝脏线粒体功能，包括氧化磷酸化、脂肪酸氧化能力、肉碱棕榈酰转移酶I（CPT I）的动力学参数以及CPT I对丙二酰辅酶A抑制的敏感性。LPS处理大鼠的肝脏线粒体CPT I对棕榈酰辅酶A的表观最大速度（Vmax）较低，对丙二酰辅酶A的抑制常数（Ki）较低，而对棕榈酰辅酶A的表观米氏常数（Km）无变化。棕榈酰-L-肉碱和辛酸的耗氧率或终产物生成率未改变，但当通过β-氧化产生的乙酰辅酶A导向柠檬酸时，LPS降低了CPT I依赖的棕榈酰辅酶A（加L-肉碱）氧化率。当乙酰辅酶A导向乙酰乙酸时，尽管线粒体3-羟基-3-甲基戊二酰辅酶A合酶活性未改变，但LPS降低了棕榈酰-L-肉碱和棕榈酰辅酶A（加L-肉碱）的耗氧率。这些结果表明，与禁食对照组相比，LPS处理大鼠分离的肝脏线粒体显示出较低的生酮和长链酰基辅酶A氧化能力，并且除了CPT I活性降低外，在CPT I远端的位点也引发了酮生成的抑制。
