Symposium on Aldo-Keto Reductases & Toxicant Metabolism

描述（由申请人提供）： 本提案是为将于2002年8月18日至22日在马萨诸塞州波士顿举行的美国化学学会全国会议上提交的为期半天的“醛酮还原酶（AKR）在有毒物质代谢中的新作用”专题讨论会提供财政支持的请求。 AKR是单体氧化还原酶的超家族，其在醛糖-糖、甘草素、类固醇激素和化学致癌物的代谢中起中心作用。 它们通常催化羰基转化为醇，使得母体化合物可以共轭和消除。 AKR在原核生物和真核生物中都高度保守。 目前有150种蛋白质分为12个家族，许多蛋白质存在晶体结构。 在人类中，这些酶还催化高渗糖的形成，由脂质氢过氧化物分解产生的反应性α，β-不饱和醛的解毒，以及包括黄曲霉毒素二醛、尼古丁衍生的亚硝胺酮和多环芳族反式二氢二醇的化学致癌物的代谢。 它们在内源性和外源性毒素代谢中的新作用表明，该家族可能最终与药物和异源生物质代谢中研究充分的peptide超家族一样重要。 本次研讨会选定的发言者将涵盖所列的每个领域。 此外，AKR超家族及其命名法（被人类基因组计划接受）的概述将被给出，并将介绍研究酵母中AKR功能基因组学的方法。 每个演讲者都在其专业领域享有国际声誉。 研讨会的目标是将AKR领域的专家聚集在一起，以便他们能够教育科学界关于这些酶，希望吸引新的研究人员到该领域。 尚未探讨的问题包括AKR亚型在药物代谢中的作用;它们在化疗药物耐药性中的作用;人类AKR基因的调节;以及AKR药物基因组学，重点是可能影响个体对毒物的反应和对化学致癌作用的易感性的人类多态性。

DESCRIPTION (provided by applicant): This proposal is a request for financial support for a half-day symposium on "The Emerging Role of Aldo-keto reductases (AKRs) in the Metabolism of Toxic Substances" to be presented at the American Chemical Society National Meeting, Boston, MA August 18-22nd, 2002. AKRs are a superfamily of monomeric oxidoreductases that play central roles in the metabolism of aldose-sugars, prostaglandins, steroid hormones, and chemical carcinogens. Often they catalyze the conversion of carbonyl groups to alcohols so that the parent compound can be conjugated and eliminated. AKRs are highly conserved in both prokaryotes and eukaryotes. There are currently 150 proteins classified into 12 families and crystal structures exist for many of the proteins. In humans, these enzymes also catalyze the formation of hyperosmotic sugars, the detoxification of reactive a,B-unsaturated aldehydes that result from the decomposition of lipid hydroperoxides, and the metabolism of chemical carcinogens including aflatoxin dialdehyde, nicotine derived nitrosamino-ketones and polycyclic aromatic trans-dihydrodiols. Their emerging role in the metabolism of endogenous and exogenous toxins suggests that the family may be ultimately as important as the well-studied CYP superfamily in drug and xenobiotic metabolism. The speakers chosen for this symposium will cover each of the areas listed. In addition an overview of the AKR superfamily and its nomenclature (accepted by the Human Genome Project) will be given and approaches to studying functional genomics of AKRs in yeast will be presented. Each of the speakers has an international reputation in their area of expertise. The goal of the symposium will be to bring together experts in the AKR field so that they will be able to educate the scientific community concerning these enzymes with the hope of attracting new investigators to the field. Issues that are unexplored include the role of AKR isoforms in drug metabolism; their role in chemotherapeutic drug resistance; the regulation of human AKR genes; and AKR pharmacogenomics with emphasis on human polymorphisms that may affect individual response to toxicants and susceptibility to chemical carcinogenesis.