DIETARY REGULATING BRANCHED CHAIN AMINO ACID METABOLISM

描述（主要研究者摘要）：广泛和长期的 本资助申请中提出的研究目标是 膳食碳水化合物调节支链氨基酸代谢的研究 和脂质。 增加 通过施用以下任一种药物， 氯贝特，细胞因子（例如，肿瘤坏死因子）或类固醇激素， 大鼠 更具体地说，研究人员计划调查 膳食碳水化合物和脂肪对支链氨基酸蛋白质利用率的影响 BCAA合成和形成氧化以及对蛋白质后BCAA释放的影响 降解 特别是，他们的研究将集中在氧化的 亮氨酸和缬氨酸转化为各种碳碎片 和肌肉，肝脏和肌肉的亚细胞部分，如 线粒体、胞质溶胶和过氧化物酶体。 改变的机制 氧化的每一步都将通过研究相关的 酶，包括BCAA转氨酶、BCKA脱氢酶、BCKA脱氢酶 激酶、异戊酰辅酶A脱氢酶和3-甲基巴豆酰辅酶A羧化酶， 和2-甲基支链酰基-Co脱氢酶。 考虑到 BCKA脱氢酶在BCAA氧化调节中的重要性，这些 研究将集中在这种酶的活性上。 BCKA的活性 脱氢酶通过酶的磷酸化-去磷酸化而改变 蛋白 研究人员计划调查营养的影响 这种调节BCCA氧化的分子机制。 最后 研究人员计划研究结果的临床应用， 在老鼠身上的研究。 热量组合物的效率，如 在大鼠研究中测定，将研究维持 患者大手术后蛋白质和支链氨基酸代谢的参数 胃肠道癌 这些研究的结果将提供 关于a）支链氨基酸代谢的新信息，其占每日 必需氨基酸的需要和B）适当设计的组合物， 为蛋白质缺乏症患者提供热量来源。

DESCRIPTION (Principal Investigator's Abstract): The broad and long-term objective of the research proposed in this grant application is the investigation of the regulation of BCAA metabolism by dietary carbohydrate and lipid when catabolism of body protein is increased. An increase in body protein catabolism would be induced by administration of either clofibrate, cytokines (e.g., Tumor Necrosis Factor), or steroid hormone to rats. More specifically, the investigators plan to investigate the effect of dietary carbohydrate and fat on utilization of BCAA for protein synthesis and for oxidation and on release of BCAA following protein degradation. In particular, their studies will focus on oxidation of leucine and valine to various carbon fragments by whole body, intact liver and muscle, subcellular fractions of liver and muscle, such as mitochondria, cytosol, and peroxisomes. The mechanism of alteration of each step in oxidation will be investigated by the study of associated enzyme, including BCAA transaminase, BCKA dehydrogenase, BCKA dehydrogenase kinase, isovaleryl-CoA dehydrogenase, and 3-methylcrotonyl-CoA carboxylase, and 2-methyl branched chain acyl-Co dehydrogenase. In view of the importance of BCKA dehydrogenase in regulation of BCAA oxidation, these studies will focus on the activity of this enzyme. The activity of BCKA dehydrogenase is altered by phosphorylation-dephosphorylation of the enzyme protein. The investigators plan to investigate the influence of nutrition on this molecular mechanism of regulation of BCCA oxidation. Finally, the investigators plan to investigate a clinical application of the result of these studies in rats. The efficiency of the caloric composition, as determined in studies in rats, will be investigated for maintaining parameters of protein and BCAA metabolism after a major surgery in patients with gastrointestinal cancer. The results of these studies will provide new information on a) metabolism of BCAA which comprises 46% of daily requirement of essential amino acids and b) proper design of composition of calorie source for patients with protein catabolism.