CHRONIC ALCOHOLISM & LIVER ENERGY & LIPID METABOLISM

我的酒精中毒相关研究的主要目的是 描述由以下原因引起的肝脏相关病理 长期的酒精消费。主要的努力将是一个 肝脏能量变化的研究 酒精性脂肪肝早期(脂肪肝)的代谢 肝病。我们之前的研究记录了几个 乙醇引起的肝线粒体损伤。完好无损的 现在将对肝细胞进行研究，以确定抑郁症是否 在体外观察到的线粒体功能对 肝细胞的能量状态。实验的目的是为了 确定1)乙醇引起的肝细胞能量变化 新陈代谢和2)体内功能的变化 线粒体。类似的措施将在以下方面实施 以确定中心周围和门静脉周围的肝细胞 乙醇引起的肝脏能量代谢的改变是 在震中周围大于门静脉周围区域 小叶。这些研究应提供必要的信息 对酒精所致中枢周围缺氧的建议进行评估 是酒精性肝病发生的病因之一 疾病。 上述调查旨在确定变更情况 在肝脏细胞和细胞器水平的能量代谢中， 将伴随着一系列研究，以调查 乙醇作用的分子机制(S)(S) 线粒体的结构和功能。的影响 慢性酒精摄入对线粒体结构的影响 由于我们已经获得了证据，将会确定ATP合成酶 它的催化性能和亚基组成 这种酶在酒精喂养的大鼠体内发生了变化。 还将进行研究，以确定 乙醇对线粒体基因组表达的影响。现在有了 有证据表明这些编码在细胞表面的多肽 线粒体基因组在肝脏中的含量较低 来自乙醇喂养的动物的线粒体。中描述的研究 这项提议旨在确认，这确实是 凯斯。还概述了实验以确定乙醇是否 消费通过以下方式抑制这些多肽的生物合成 正在更改抄写。这些关于乙醇影响的研究 关于膜相关多肽将补充广泛的 目前正在进行调查，以建立这种关系 乙醇对细胞膜脂质的影响与改变的关系 在膜功能方面。

The major objective of my alcoholism-related research is to characterize the liver associated pathology which results from chronic ethanol consumption. The major effort will be an investigation of those changes that occur in hepatic energy metabolism during the early (fatty liver) stage of ethanol-induced liver disease. Our previous studies have documented several ethanol-induced lesions in liver mitochondria. The intact hepatocyte will now be investigated to determine if the depression in mitochondrial function observed in vitro adversely affects the energy state of the liver cell. Experiments are designed to determine 1) ethanol-elicited alterations in hepatocyte energy metabolism and 2) changes in the in vivo functioning of the mitochondrion. Similar measurements will be implemented with pericentral and periportal hepatocytes to determine whether ethanol-elicited alterations in hepatic energy metabolism are greater in the pericentral than the periportal region of the lobule. These studies should provide information needed to evaluate the suggestion that ethanol-induced pericentral hypoxia is an etiological factor in development of alcohol-induced liver disease. The above investigation, which is designed to determine alterations in hepatic energy metabolism at the cellular and organelle levels, will be accompanied by a series of studies to investigate the molecular mechanism(s) by which ethanol elicits its effect(s) on the structure and function of the mitochondrion. The effect of chronic ethanol consumption on the structure of the mitochondrial ATP synthase will be determined since we have obtained evidence that both the catalytic properties and the subunit composition of this enzyme are altered in ethanol-fed rats. Studies will also be carried out to determine the effects of ethanol on expression of the mitochondrial genome. There is now evidence that suggests that those polypeptides encoded on the mitochondrial genome are present in lowered amounts in liver mitochondria from ethanol-fed animals. The studies described in this proposal are designed to confirm that this is, indeed, the case. Experiments are also outlined to determine if ethanol consumption depresses the biosynthesis of these polypeptides by altering transcription. These studies of the effects of ethanol on membrane-associated polypeptides will complement the extensive investigations currently in progress to establish the relationship between ethanol-elicited effects on membrane lipids and alterations in membrane function.