（+）-半棕榈酰肉碱鎓在完整线粒体中强烈抑制肉碱棕榈酰转移酶-I。
(+)-Hemipalmitoylcarnitinium strongly inhibits carnitine palmitoyltransferase-I in intact mitochondria.
作者信息
Gandour R D, Leung O T, Greway A T, Ramsay R R, Nic a'Bháird N, Fronczek F R, Bellard B M, Kumaravel G
机构信息
Department of Chemistry, Louisiana State University, Baton Rouge 70803-1804.
出版信息
J Med Chem. 1993 Jan 22;36(2):237-42. doi: 10.1021/jm00054a007.
The reaction of the methyl ester of (R)-norcarnitine with 1-bromo-2-heptadecanone produces (+)-6-[(methoxycarbonyl)methyl]-2-pentadecyl-4,4-dimethylmorpholinium bromide, 3, which hydrolyzes to (+)-6-(carboxylatomethyl)-2-pentadecyl-4,4-dimethylmorpholinium (hemipalmitoylcarnitinium, HPC) upon treatment with aqueous sodium hydroxide. Single-crystal X-ray analyses have confirmed the structures of (+)-HPC and 3. (+)-HPC inhibits carnitine palmitoyltransferase (CPT-I) activity for the forward reaction (palmitoyl-CoA + carnitine-->) in intact mitochondria from rat heart and rat liver. (+)-HPC competitively (versus carnitine) inhibits CPT-I activity in both rat heart and liver mitochondria with Ki = 2.8 +/- 0.5 and 4.2 +/- 0.7 microM, respectively. As one of the strongest specific inhibitors of CPT-I, HPC is a potential therapeutic agent in myocardial ischemia and Type II diabetes.
(R)-去甲肉碱甲酯与1-溴-2-十七烷酮反应生成(+)-6-[(甲氧基羰基)甲基]-2-十五烷基-4,4-二甲基吗啉溴化物（3），用氢氧化钠水溶液处理后，3水解生成(+)-6-(羧甲基)-2-十五烷基-4,4-二甲基吗啉（半棕榈酰肉碱鎓，HPC）。单晶X射线分析已证实(+)-HPC和3的结构。(+)-HPC抑制大鼠心脏和大鼠肝脏完整线粒体中肉碱棕榈酰转移酶（CPT-I）正向反应（棕榈酰辅酶A + 肉碱 -->）的活性。(+)-HPC在大鼠心脏和肝脏线粒体中均竞争性（相对于肉碱）抑制CPT-I活性，其Ki分别为2.8±0.5和4.2±0.7 microM。作为CPT-I最强的特异性抑制剂之一，HPC是心肌缺血和II型糖尿病的潜在治疗药物。
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