DISTRIB OF FLUX CONTROL BETWEEN ADH AND ALDH LIVER ETHANOL METABOLISM

ADH 和 ALDH 肝脏乙醇代谢之间通量控制的分布

• 批准号: 7609921
• 负责人: Jennifer R Chase
• 金额: $ 3.08万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609921
• 关键词: Acetaldehyde; Alcohol Dehydrogenase I; Alcohol dehydrogenase; Aldehyde dehydrogenase (NAD+); Buffers; Class; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Elasticity; Equus caballus; Ethanol Metabolism; Funding; Grant; Human; Institution; Investigation; Kinetics; Liver; Measures; Metabolic Control; Pathway interactions; Physiological; Protein Isoforms; Range; Rate; Relative (related person); Research; Research Personnel; Resources; Retinoids; Source; United States National Institutes of Health; Vitamin A; Work; aldehyde dehydrogenase 1; aldehyde dehydrogenases; comparative; in vitro Assay; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Distribution of flux control between alcohol dehydrogenase (ADH) and ALDH liver ethanol metabolism We propose to quantify the distribution of control of the flux in the liver alcohol metabolism pathway between the many isoforms of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). The framework for the investigation will be Metabolic Control Analysis (MCA). For this investigation we will quantify the relative control of ADH and ALDH using the parallel tracks of in vitro assays of ADH and ALDH, in physiological buffer and computer simulations. We will determine the elasticities of the various forms of ADH and ALDH from human and horse livers. Further work will incorporate ALDH and kinetic studies on ALD and ALDH with vitamin A derivatives. The following specific aims will be studied: 1) To determine whether all forms of human class I ADH have equal elasticity with acetaldyhyde; 2) To determine whether all forms of human class I ADH and ALDH have equal elasticity to acetaldehyde; 3) To compare elasticity of ADH isoforms measured from in vitro assays with calculated rate constants; 4) To measure elasticities of all forms of ADH to retinoids in response to EtOH over the physiological range; 5) To measure elasticities of ALDH1 to retinoids with changes in EtOH over the physiological range; and 6) To determine the comparative elasticity between ALDH1 and ALDH11 to retionoids over the physiological range.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 乙醇脱氢酶 (ADH) 和 ALDH 肝脏乙醇代谢之间的通量控制分布 我们建议量化酒精脱氢酶（ADH）和乙醛脱氢酶（ALDH）的多种异构体之间肝脏酒精代谢途径中流量控制的分布。该研究的框架将是代谢控制分析（MCA）。在这项研究中，我们将使用生理缓冲液和计算机模拟中 ADH 和 ALDH 体外测定的平行轨迹来量化 ADH 和 ALDH 的相对控制。我们将测定人和马肝脏中各种形式的 ADH 和 ALDH 的弹性。进一步的工作将结合 ALDH 以及 ALD 和 ALDH 与维生素 A 衍生物的动力学研究。 将研究以下具体目标： 1) 确定所有形式的人类 I 类 ADH 是否与乙醛具有相同的弹性； 2) 确定所有形式的人类I类ADH和ALDH是否对乙醛具有相同的弹性； 3) 将体外测定中测量的 ADH 亚型的弹性与计算的速率常数进行比较； 4) 测量生理范围内所有形式的 ADH 对类维生素A响应 EtOH 的弹性； 5) 在生理范围内测量 ALDH1 对类视黄醇的弹性随 EtOH 的变化； 6) 确定 ALDH1 和 ALDH11 与维甲酸在生理范围内的比较弹性。