DIETARY REGULATING BRANCHED CHAIN AMINO ACID METABOLISM

说明(首席调查员摘要)：广泛和长期 在这项拨款申请中提出的研究目标是 膳食碳水化合物对支链氨基酸代谢调控的研究 当体内蛋白质分解代谢增加时，脂肪含量增加。增加了…… 人体蛋白质分解代谢可通过服用这两种药物之一来诱导 氯贝特、细胞因子(如肿瘤坏死因子)或类固醇激素 老鼠。更具体地说，调查人员计划调查这一影响 碳水化合物和脂肪对支链氨基酸利用蛋白质的影响 蛋白质支链氨基酸的合成、氧化和释放 退化。特别是，他们的研究将集中在氧化 亮氨酸和缬氨酸被全身、完整的肝脏分解为各种碳碎片 和肌肉，肝脏和肌肉的亚细胞部分，如 线粒体、胞浆和过氧化物体。三个方面的变化机制 氧化的每一步都将通过相关的研究进行调查 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羧基酶， 2-甲基支链酰基-钴脱氢酶。鉴于 BCKA脱氢酶在调节支链氨基酸氧化中的重要性 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 关于BCCA氧化调控的分子机制。最后， 研究人员计划调查这一结果的临床应用 这些在老鼠身上的研究。卡路里组成的效率，如 在老鼠身上的研究中确定的，将被调查以维持 大手术后患者蛋白质和支链氨基酸代谢参数的变化 患有胃肠道癌症。这些研究的结果将提供 关于支链氨基酸代谢的新信息，占每日代谢的46% 必需氨基酸的需求和b)正确的成分设计 蛋白质分解代谢患者的热量来源。

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.