CORE--STRUCTURAL AND CELLULAR BIOLOGY

乙醇的药理学和毒理学作用部分是 由乙醇代谢速率和 乙醇代谢物（乙醛、乙酸盐和NADH）。 水平 这些代谢物由醇和醛的活性决定 代谢酶 结构生物学核心实验室提供了 重组醇和醛的合成服务 代谢酶和X射线晶体学分析纯 proteins.在未来的支持期内， 由独立资助的研究人员进行的研究， 扩展了这一点和分子生物学核心在 前几个供资期。 核心的基础研究问题 这是酒精摄入率的结构决定因素， 醛氧化和不同人的底物特异性 酒精和乙醛脱氢酶 开发研究工具， 进一步解决这些重要问题将是服务的重点 在下一个供资期内， 核心将继续 提供上述服务。特别是，它将支持 ALDH 2晶体结构溶液的最终相。 在一个新 方向，它将支持表达酒精的细胞的产生， 醛脱氢酶作为醇和醛的模型 新陈代谢.这些细胞将用于阐明 测定各种醇和醛的代谢率 (e.g.,类维生素A）。 这些研究将有助于更好地了解 已知的酶变体对酒精代谢的影响， 乙醇对这种代谢的影响。 表达其他蛋白质的细胞 与酒精研究有关的信息也将产生。

The pharmacological and toxicological effects of ethanol are in part determined by the rate of ethanol metabolism and the concentration of alcohol metabolites (acetaldehyde, acetate, and NADH). The levels of these metabolites are determined by the activities of alcohol and aldehyde metabolizing enzymes. The Structural Biology Core laboratory has offered services for the synthesis of recombinant alcohol and aldehyde metabolizing enzymes and for X-ray crystallographic analysis of pure proteins. In the coming period of support, this Core will also support research carried out by investigators with independent funding that will extend observations made by this and the Molecular Biology Core in the previous funding periods. The fundamental research question of the core has been: That are the structural determinants for the rate of alcohol or aldehyde oxidation and the substrate specificity for the different human alcohol and aldehyde dehydrogenases? The development of research tools to further address these important issues will be the focus of services provided by the Core in the coming funding period. The Core will continue to offer the services mentioned above. In particular, it will support the final phase of the crystal structure solution of ALDH2. In a new direction, it will support the generation of cells expressing alcohol and aldehyde dehydrogenases to serve as models of alcohol and aldehyde metabolism. These cells will be utilized to elucidate the factors that determine the rates of metabolism of a variety of alcohols and aldehydes (e.g., retinoids). These studies will provide a better understanding of the effects of the known enzyme variants on alcohol metabolism and the effects of ethanol on this metabolism. Cells expressing other proteins relevant to alcohol research will also be generated.