IMPACT OF ETHANOL ON OXIDATION OF METABOLITES

乙醇对代谢物氧化的影响

• 批准号: 7720020
• 负责人: Jennifer R Chase
• 金额: $ 5.57万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720020
• 关键词: Acetaldehyde; Alcohol Dehydrogenase I; Alcohol dehydrogenase; Aldehyde dehydrogenase (NAD+); All-Trans-Retinol; Biological Assay; Buffers; Class; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Cultured Cells; Elasticity; Enzymes; Equus caballus; Ethanol; Ethanol Metabolism; Funding; Grant; Human; In Vitro; Institution; Investigation; Kinetics; Liver; Mammals; Measures; Metabolic Control; Pathway interactions; Physiological; Process; Protein Isoforms; Range; Rate; Relative (related person); Research; Research Personnel; Resources; Retinoids; Source; Tretinoin; United States National Institutes of Health; Vitamin A; Work; aldehyde dehydrogenase 1; aldehyde dehydrogenases; comparative; in vitro Assay; oxidation; 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. Ethanol interferes with normal retinoid processing at several different pathways in mammals. We utilize computational modeling, in vitro enzyme assays, and cell culture to understand the mechanism by which ethanol disrupts the synthesis of retinoic acid from retinol through alcohol dehydrogenases. 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 retinoids over the physiological range.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 乙醇在哺乳动物的几种不同途径上干扰类黄纳生动物的正常加工。我们利用计算建模，体外酶测定和细胞培养物来了解乙醇破坏视黄醇通过酒精脱氢酶从视黄醇合成的机制。 酒精脱氢酶（ADH）和ALDH肝乙醇代谢之间通量控制的分布 我们建议量化肝酒代谢途径中通量的控制分布，这是酒精脱氢酶（ADH）和醛脱氢酶（ALDH）的许多同工型之间的控制。调查的框架将是代谢控制分析（MCA）。在此研究中，我们将使用ADH和ALDH的平行轨道在生理缓冲和计算机模拟中量化ADH和ALDH的相对控制。我们将确定人和马肝脏中各种形式的ADH和ALDH的弹性。进一步的工作将与维生素A衍生物有关ALD和ALDH的ALDH和动力学研究。 将研究以下具体目标：1）确定所有形式的人类I级ADH是否具有与乙酰醛相等的弹性； 2）确定所有形式的人类I ADH和ALDH是否具有与乙醛相等的弹性； 3）比较通过计算出的速率常数测量的ADH同工型的弹性； 4）在生理范围内测量各种形式的ADH对类视黄素的弹性； 5）测量ALDH1的弹性对视视视网想中的eTOH变化； 6）为了确定ALDH1和ALDH11与生理范围内的类视黄素之间的比较弹性。