Tuning-Up Human Metabolism

调节人体新陈代谢

• 批准号: 6694095
• 负责人: Bruce N Ames
• 金额: $ 25.69万
• 依托单位: CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6694095
• 关键词: Asians; DNA damage; aerobiosis; aging; alcohols; clinical research; clinical trials; cofactor; dosage; drug tolerance; genetic disorder; genetic polymorphism; homocysteine; human old age (65+); human subject; human therapy evaluation; inborn metabolism disorder; longitudinal human study; mitochondrial DNA; mutant; niacin; nutrition related tag; riboflavin; vitamin B complex; vitamin metabolism; vitamin therapy

DESCRIPTION (provided by applicant): K05 Senior Scientist Grant (NCCAM). Ames has published more than 450 publications and consistently ranks among the top few hundred of the most-cited-scientists in all fields; honors include The National Medal of Science & The Japan Prize. Career as pioneer/leader in: gene-regulation; genetic toxicology; mutagenesis; cancer prevention; endogenous oxidants/antioxidants; nutrition and health; mitochondrial decay; and aging. Professor of the Graduate School at U.C. Berkeley. Senior Scientist, Children's Hospital of Oakland Research Institute, with large lab in a newly renovated building. Scientific focus: ramifications of a major review showing that about 50 different human genetic diseases due to a poorer binding affinity (Km) of the mutant enzyme for the coenzyme, can be remedied by feeding high dose B vitamins which raise levels of the corresponding coenzyme; many polymorphisms also have lowered affinity of enzyme for coenzyme. We propose to expand this Km concept by: 1) Testing the effectiveness of high dose B vitamins on phenotypes caused by polymorphisms that affect the Km of enzymes for coenzyme, e.g. homocysteine accumulation in MTHFR: riboflavin; alcohol intolerance in half of Asians: niacin. 2) Testing the effectiveness of other metabolites and micronutrients.3) Determining if mitochondrial oxidative decay with age causes enzymes to lose affinity for their coenzymes and if this can be ameliorated by feeding high doses of B vitamins. Previous results showed that high doses of key mitochondrial metabolites delay mitochondrial decay and involve Km. 4) Minimizing DNA damage and cancer by optimizing micronutrient levels, particularly in the elderly.

描述（由申请人提供）：K05高级科学家Grant（NCCAM）。埃姆斯（Ames）发表了450多个出版物，并始终在所有领域中最引人注目的科学家中排名前几位。荣誉包括国家科学和日本奖。作为先驱/领导者的职业：基因调节；遗传毒理学；诱变；预防癌症；内源性氧化剂/抗氧化剂；营养和健康；线粒体衰减；和老化。 U.C.研究生院教授伯克利。 奥克兰研究所儿童医院高级科学家，在一座新装修的建筑物中，大型实验室。 科学重点：一项重大综述的后果表明，由于辅酶的突变酶的结合亲和力（Km）较差，可以通过喂养高剂量B族维生素来补救，从而弥补了相应辅酶的水平；许多多态性也降低了酶对辅酶的亲和力。 我们建议通过以下方式扩展这种KM概念：1）测试高剂量B族维生素对影响辅酶的酶Km的多态性引起的表型的有效性，例如MTHFR中的同型半胱氨酸积累：核黄素；一半亚洲人的酒精不耐受：烟酸。 2）测试其他代谢产物和微量营养素的有效性。3）确定线粒体氧化衰减是否会导致酶对辅酶失去亲和力，并且是否可以通过喂养高剂量的B脂肪蛋白来改善这一点。先前的结果表明，高剂量的关键线粒体代谢产物延迟线粒体衰减，并涉及KM。 4）通过优化微量营养素水平，特别是在老年人中，最大程度地减少了DNA损伤和癌症。