Brady L J, Brady P S
Department of Food Science and Human Nutrition, Washington State University, Pullman 99164-2032.
Biochem Pharmacol. 1987 Oct 15;36(20):3419-23. doi: 10.1016/0006-2952(87)90320-0.
Carnitine palmitoyltransferase (CPT) activity is located on both the outer and inner sides of the mitochondrial inner membrane and is influenced by the surrounding lipids of the inner mitochondrial membrane. Both adriamycin and galactosamine interact with mitochondrial lipids as a part of their mechanism of toxicity, and thus these agents might be expected to affect CPT activity. Addition of adriamycin to both intact rat liver and heart mitochondria (CPT-A, outer CPT) and inverted submitochondrial vesicles (CPT-B, inner CPT) depressed CPT in the forward direction of reaction (palmitoyl-l-carnitine formation), but the CPT-B activity was more sensitive to the inhibitor. Adriamycin depressed the CPT-A reverse reaction (palmitoyl-CoA formation) to 40% of control, but it had no effect on the CPT-B reverse reaction. In vivo galactosamine administration depressed CPT-A and CPT-B 20-30% and did not affect subsequent action of in vitro adriamycin. Addition of cardiolipin (0.25 to 1.0 mg/assay) increased activity of the CPT-A forward reaction of both control and galactosamine-treated rats, but it did not affect CPT-B activity. The results suggest that CPT-A and CPT-B may be influenced differently by perturbants that affect lipids of the membrane.
肉碱棕榈酰转移酶（CPT）活性位于线粒体内膜的外侧和内侧，受线粒体内膜周围脂质的影响。阿霉素和半乳糖胺作为其毒性机制的一部分，会与线粒体脂质相互作用，因此预计这些药物会影响CPT活性。将阿霉素添加到完整的大鼠肝脏和心脏线粒体（CPT-A，外CPT）以及反向亚线粒体囊泡（CPT-B，内CPT）中，会抑制反应正向（棕榈酰-L-肉碱形成）的CPT，但CPT-B活性对抑制剂更敏感。阿霉素将CPT-A的反向反应（棕榈酰辅酶A形成）抑制至对照的40%，但对CPT-B的反向反应没有影响。体内给予半乳糖胺会使CPT-A和CPT-B降低20 - 30%，且不影响随后体外阿霉素的作用。添加心磷脂（0.25至1.0毫克/测定）可增加对照和半乳糖胺处理大鼠CPT-A正向反应的活性，但不影响CPT-B活性。结果表明，影响膜脂质的干扰物对CPT-A和CPT-B的影响可能不同。
