BRANCHED AMINO ACID METABOLISM IN ALTERED NUTRITION

支链氨基酸(BCAA)，除了占每日摄入量的46% 对人体必需氨基酸的需求，可能在 代谢调节。这些包括肌肉中的蛋白质周转，释放 外周组织丙氨酸和谷氨酰胺、葡萄糖氧化与脑 神经递质的合成。我们和其他人的研究表明 支链氨基酸的代谢又受饮食和营养的调节。 各种因素。例如，在低卡路里饮食的同时，饥饿会增加 碳水化合物饮食减少，支链氨基酸分解代谢。尽管已经有了 膳食和代谢因素识别的研究进展 改变支链氨基酸代谢和这些改变的机制 根本问题要么没有得到解决，要么还没有被探索。例如, 为什么碳水化合物在短暂饥饿时不会分解支链氨基酸 胖子不是吗？要回答这个问题和其他相关问题，请使用人类和 以大鼠为实验模型，以下8个相关研究项目 研究结果如下：1.碳水化合物和脂肪对大鼠支链氨基酸代谢的影响 长期饥饿与短暂饥饿(人类)。2.碳水化合物与 脂肪对支链氨基酸代谢的影响(人)。3.支链氨基酸在土壤中的代谢 糖尿病(男性)。4.膳食改变支链氨基酸代谢的机制 碳水化合物和脂肪(大鼠)。5.支链氨基酸代谢的变化机制 在甲亢和甲减(大鼠)中。6.肉碱对氧化的影响 BCAA的体外和体内(大鼠)。7.支链氨基酸在脂类中的代谢 合成受到抑制(大鼠)。8.饥饿、糖尿病和 氯贝特对大鼠异戊酸酯代谢的影响。我们的整体 假设支链氨基酸的分解代谢受 能量代谢，而且，这两个代谢过程是 由各种化学信号相互连接，其中浓度 亮氨酸中，酮体和三磷酸腺苷的含量最高。 最后，对选择性影响的疾病进行临床观察 支链氨基酸的氧化表明支链氨基酸分解代谢的精确调控是 为避免受损或增强的有害影响所必需的 这些氨基酸的氧化。申请书中提出的研究 旨在回答有关这一规定的基本问题。 拟议的研究所寻求的信息可能有助于更好地 对常见代谢性疾病发病机制及治疗的认识 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.