ETHANOL CONSUMPTION AND LIVER AND BRAIN METABOLISM

有机体中与酒精相关的改变的基础是密切相关的 与乙醇的新陈代谢和乙醇引起的变化有关 正常的代谢途径。虽然这一原则适用于所有 受酒精影响的器官，不同组织的反应可能有所不同 广泛地。因此，研究与乙醇有关的新陈代谢 重点研究了不同器官的不同反应。这些研究 本高级科学家奖申请书中包含的内容包括 针对乙醇对肝脏和肝脏代谢系统的影响 大脑。 关于肝脏研究，主要目标是联系 酒精性肝病发生发展过程中的代谢变化。 包括关于乙醇对1)完整性的影响的研究 线粒体氧化磷酸化系统及2)合成 通过糖酵解途径。包括实验，以检验 乙醇引起的上述机制的改变如何影响 肝细胞的结构和功能的完整性。相互影响 在乙醇中的氧化应激和细胞能量状态之间- 肝细胞活性的相关丧失也将被评估。 大脑中的新陈代谢研究对我来说是一个新领域， 专注于建立血糖和神经递质的变化 伴随着行为变化发生的新陈代谢 个体自行给药乙醇。细胞的合成途径 氨基酸和生物胺神经递质将在#年进行研究 一种啮齿动物自我管理模式。为老年人服务的目的 科学家申请是为了获得足够的研究时间，让我 在我保持电流的同时添加神经递质新陈代谢研究 我在肝脏乙醇项目上的努力。

The basis for ethanol-related alterations in the organism is intimately linked to the metabolism of ethanol and the changes ethanol elicits in normal metabolic pathways. While this principle is applicable in all organs affected by ethanol, the response in different tissues can vary widely. Thus, a study of the metabolism associated with ethanol can be focused on different responses in different organs. The studies encompassed in this application for a Senior Scientist award are directed toward the effects of ethanol on metabolic systems in liver and brain. With regard to the liver studies, the major goal is to relate alterations in metabolism to development of alcoholic liver disease. Included are studies of the effects of ethanol on 1) the integrity of the mitochondrial oxidative phosphorylation system and 2) the synthesis of ATP via the glycolytic pathway. Experiments are included to examine how ethanol-elicited alterations in the above mechanisms affect the structural and functional integrity of the hepatocyte. The interplay between oxidative stress and cellular energy state in the ethanol- related loss of hepatocyte viability will also be evaluated. The metabolic studies in the brain, which are a new area for me, are focused on establishing alterations in glucose and neurotransmitter metabolism that accompany the behavioral changes occurring when an individual self-administers ethanol. The synthetic pathways for the amino acid and biogenic amine neurotransmitters will be investigated in a rodent self-administration model. The purpose for the Senior Scientist application is to obtain enough research time to allow me to add the neurotransmitter metabolism study while I maintain current effort on my liver-ethanol program.