Smith C M, Israel B C, Iannucci J, Marino K A
J Nutr. 1987 Mar;117(3):452-9. doi: 10.1093/jn/117.3.452.
Ethanol, both administered to rats in vivo and added to cultured hepatocyte incubations, inhibits the conversion of [14C]pantothenate to coenzyme A (CoA). Data suggesting that the inhibition by ethanol involves its oxidation to acetate were obtained with rat hepatocytes maintained in primary culture. Ethanol, acetaldehyde and acetate were approximately equally effective inhibitors of [14C]pantothenate conversion to CoA (46-71%) and had no effect on uptake of [14C]pantothenate by hepatocytes. In the presence of saturating levels of acetate, acetaldehyde had no additional inhibitory effect. Cyanamide and diethyldithiocarbamate decreased the inhibition by acetaldehyde at the same concentration (10 microM), which saturated their ability to inhibit acetaldehyde oxidation. Studies with an isolated pantothenate kinase preparation showed that, of the ethanol metabolites, only acetyl-CoA was an effective inhibitor. Acetate and butyrate, which were both inhibitors of [14C]pantothenate conversion to CoA, increased the acetyl-CoA and decreased the free, unacylated CoA (CoASH) content of the cultured hepatocytes. The data were consistent with a mechanism for the inhibitory effect of ethanol that involves inhibition of pantothenate kinase by acetyl-CoA, but did not exclude a possible role of additional regulatory factors.
无论是在体内给大鼠施用乙醇，还是将其添加到培养的肝细胞培养液中，乙醇都会抑制[14C]泛酸盐向辅酶A（CoA）的转化。在原代培养的大鼠肝细胞实验中，获得了表明乙醇抑制作用涉及其氧化成乙酸盐的数据。乙醇、乙醛和乙酸盐对[14C]泛酸盐转化为CoA的抑制作用大致相同（46%-71%），且对肝细胞摄取[14C]泛酸盐没有影响。在乙酸盐饱和水平存在的情况下，乙醛没有额外的抑制作用。氨基氰和二乙基二硫代氨基甲酸盐在相同浓度（10微摩尔）下可降低乙醛的抑制作用，该浓度使它们抑制乙醛氧化的能力达到饱和。对分离的泛酸盐激酶制剂的研究表明，在乙醇代谢产物中，只有乙酰辅酶A是有效的抑制剂。乙酸盐和丁酸盐都是[14C]泛酸盐转化为CoA的抑制剂，它们增加了培养肝细胞中的乙酰辅酶A含量，并降低了游离的、未酰化的CoA（CoASH）含量。这些数据与乙醇抑制作用的机制一致，即涉及乙酰辅酶A对泛酸盐激酶的抑制，但并不排除其他调节因子可能发挥的作用。
