PHYSIOLOGY OF MALONYL COA IN MUSCLE DURING EXERCISE

运动期间肌肉中丙二酰辅酶A的生理学

• 批准号: 3161880
• 负责人: WILLIAM WINDER
• 金额: $ 11.31万
• 依托单位: BRIGHAM YOUNG UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3161880
• 关键词: acetyl coA carboxylase; adrenergic agents; affinity chromatography; calmodulin dependent protein kinase; enzyme mechanism; enzyme structure; epinephrine; exercise; insulin; isolation perfusion; laboratory rat; lipid metabolism; malonyl coA; molecular weight; muscle contraction; muscle metabolism; phosphorylation; protein kinase A; striated muscles

In the liver, malonyl-CoA is the first committed intermediate in the pathway for fatty acid synthesis from glucose and other carbohydrate precursors. This compound inhibits carnitine palmitoyl transferase I (the rate limiting enzyme for fatty acid oxidation) in isolated mitochondria from both liver and skeletal muscle. In times of glucose abundance, activation of acetyl-CoA carboxylase (ACC) causes increased malonyl-CoA concentration in the liver. The high concentration of malonyl-CoA inhibits CPT I so that fatty acid oxidation is inhibited at times when glucose is being utilized for fatty acid synthesis. During times of fasting, elevated plasma glucagon inhibits (via cAMP-triggered phosphorylation) ACC resulting in a decline in malonyl-CoA in skeletal muscle (a non-lipogenic tissue). Skeletal muscle malonyl-CoA decreases markedly in response to fasting and exercise. The principal purpose of the proposed experiments is to elucidate the mechanisms of regulation of malonyl-CoA synthesis in muscle by ACC. The skeletal muscle ACC will be isolated and characterized in terms of molecular weight and kinetic properties. The roles of epinephrine, insulin, and muscle contraction in regulation of ACC will be studied using the hindlimb perfusion system. The role of phosphorylation will be studied using cAMP-dependent protein kinase, AMP-dependent protein kinase, and calcium-calmodulin dependent protein kinase II. The effect of acute exercise bouts and of endurance training on ACC will be studied in rat skeletal muscle. These studies will provide new information on regulation of muscle malonyl-CoA, a putative regulator of fat oxidation in muscle. This information will be important for better understanding the metabolic derangements of diabetes mellitus and for understanding regulation of fat utilization during exercise.

在肝脏中，丙二酰辅酶a是肝脏中第一个参与的中间体