BRANCHED AMINO ACID METABOLISM IN ALTERED NUTRITION

支链氨基酸（BCAA），除了占每日摄入量的46%之外， 人体必需氨基酸的需求，可能在以下方面发挥重要作用： 代谢调节。 这些包括肌肉中的蛋白质周转， 丙氨酸和谷氨酰胺通过外周组织、葡萄糖氧化和脑 神经递质的合成。 我们和其他人的研究表明 BCAA的代谢反过来受到饮食和营养的调节， 因素 例如，饥饿增加，而节食低热量 碳水化合物饮食减少，支链氨基酸的catenorase。 虽然出现 确定饮食和代谢因素的进展， 改变BCAA代谢和这些改变的机制，一些 一些根本性的问题仍然没有得到解决或探讨。 比如说， 为什么碳水化合物在短暂饥饿时不会分解代谢BCAA，而 脂肪不？ 为了回答这个问题和其他相关问题，使用人类和 大鼠作为实验模型，以下8个相互关联的研究项目 建议：1.碳水化合物与脂肪对大鼠支链氨基酸代谢的影响 长期饥饿与短暂饥饿（人）。 2.碳水化合物与 脂肪对BCAA代谢的影响。 3. BCAA代谢 糖尿病（男性）。 4.饮食改变支链氨基酸代谢的机制 碳水化合物和脂肪（大鼠）。 5.支链氨基酸代谢改变的机制 甲状腺功能亢进和甲状腺功能减退（大鼠）。 6.肉毒碱对氧化的影响 BCAA在体外和体内（大鼠）。 7.当脂质 合成受到抑制（大鼠）。 8.饥饿、糖尿病和 氯贝特治疗对异戊酸代谢的影响（大鼠）。 我们的整体 假设BCAA的催化作用是由状态调节的， 能量代谢，而且，这两个代谢过程 通过各种化学信号相互联系， 亮氨酸、酮体和ATP是最主要的。 最后，临床观察疾病，选择性影响 BCAA的氧化表明，BCAA催化剂的精确调节是 必须避免受损或增强的有害影响 这些氨基酸的氧化。 申请中提出的研究 旨在回答有关该法规的基本问题。 拟议的研究所寻求的信息可能有助于更好地 了解常见代谢紊乱的发病机制和治疗 如肥胖、营养不良、糖尿病、甲状腺疾病和肝脏 疾病

Branched-chain amino acids (BCAA), besides making up 46% of the daily requirement for essential amino acids in man, may have important roles in metabolic regulation. These include protein turnover in muscle, release of alanine and glutamine by peripheral tissues, glucose oxidation and brain synthesis of neurotransmitters. Our studies and those of others have shown that BCAA metabolism, in turn, is regulated by dietary and nutritional factors. For example, starvation increases, while dieting on a hypocaloric carbohydrate diet decreases, catabolism of BCAA. Although there has been progress toward identification of the dietary and metabolic factors which alter BCAA metabolism and the mechanisms of these alterations, a number of fundamental questions remain either unresolved or unexplored. For example, why does carbohydrate spare catabolism of BCAA in brief starvation while fat does not? To answer this and other related questions, using humans and rats as experimental models, the following 8 interrelated research projects are proposed: 1. Effects of carbohydrate versus fat on BCAA metabolism in prolonged versus brief starvation (man). 2. Effect of carbohydrate versus fat on BCAA metabolism in the fed state (man). 3. BCAA metabolism in diabetes (man). 4. Mechanism of alteration in BCAA metabolism by dietary carbohydrate and fat (rats). 5. Mechanism of alteration in BCAA metabolism in hyper- and hypothyroidism (rats). 6. Effect of carnitine on oxidation of BCAA in vitro and in vivo (rats). 7. Metabolism of BCAA when lipid synthesis is inhibited (rats). 8. Effect of starvation, diabetes and clofibrate treatment on metabolism of isovalerate (rats). Our overall hypothesis is that the catabolism of BCAA is regulated by the state of energy metabolism and, moreover, these two metabolic processes are interconnected by a variety of chemical signals among which concentrations of leucine, ketone bodies and ATP are the most predominant. Finally, clinical observations in diseases which selectively affect oxidation of BCAA indicate that a precise regulation of BCAA catabolism is necessary to avoid deleterious effects of either impaired or enhanced oxidation of these amino acids. The studies proposed in the application are aimed at answering fundamental questions regarding this regulation. The information sought by the proposed studies may contribute to a better understanding of pathogenesis and treatment of common metabolic disorders such as obesity, undernutrition, diabetes, thyroid disorders, and liver disease.