Molecular model of human branched-chain amino acid metabolism
Molecular model of human branched-chain amino acid metabolism
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DOI：
10.1093/ajcn/68.1.72
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发表时间：
1998-07-01
影响因子：
7.1
通讯作者：
Hutson, SM
中科院分区：
文献类型：
--
作者：
Suryawan, A;Hawes, JW;Hutson, SM
为建立准确的人支链氨基酸（BCAA）代谢的分子模型，测定了BCAA分解代谢途径中前两种酶--支链氨基酸氨基转移酶（BCAT）和支链α-酮酸脱氢酶（BCKD）复合物在人体组织中的分布、活性和表达。在大鼠和非洲绿色猴组织中测定了相同的酶活性。总体而言，大鼠组织中BCAT和BCKD的活性高于人和猴组织;然而，3个种属的大多数组织中2种活性的比例相似。总氧化能力集中在骨骼肌和肝脏（> 70%），在人类和猴子中，肌肉占总氧化能力的比例更高。在人类中，大脑（10-20%）和肾脏（8-13%）可能对全身BCAA代谢有重要贡献。此外，在灵长类动物中，整个胃肠道中转氨酶与氧化能力的高比率用于防止必需BCAA碳的损失，并提高胃肠道有助于血浆支链α-酮酸库的可能性。定量聚合酶链反应用于检测人支链α-酮酸脱氢酶激酶（BCKDK）的表达，该酶是调节人BCKD复合物和人BCAT同工酶的活性状态的关键酶。为了设计用于聚合酶链反应的引物，克隆了人BCKDK。BCKDK信息在所有测试的人体组织中均被发现，其中在人体肌肉中的含量最高。与大鼠一样，线粒体BCAT普遍表达，而胞质酶的mRNA在脑外处于或低于检测限。最后讨论了支链氨基酸在机体氮代谢中的作用。
To establish an accurate molecular model of human branched-chain amino acid (BCAA) metabolism, the distribution, activity, and expression of the first 2 enzymes in the catabolic pathway-branched-chain-amino-acid aminotransferase (BCAT) and branched-chain alpha-keto acid dehydrogenase (BCKD) complex-were determined in human tissues. The same enzyme activities were measured in rat and African green monkey tissues. Overall, the activities of BCAT and BCKD were higher in rat than in human and monkey tissues; nevertheless, the ratio of the 2 activities was similar in most tissues in the 3 species. Total oxidative capacity was concentrated in skeletal muscle and liver (> 70%) with muscle having a higher proportion of the total in humans and monkeys. In humans, brain (10-20%) and kidney (8-13%) may contribute significantly to whole-body BCAA metabolism. Furthermore, in primates the high ratio of transaminase to oxidative capacity in the entire gastrointestinal tract serves to prevent loss of essential BCAA carbon and raises the possibility that the gastrointestinal tract contributes to the plasma branched-chain cr-keto acid pool. Quantitative polymerase chain reaction was used to examine expression of human branched-chain cr-keto acid dehydrogenase kinase (BCKDK), the key enzyme that regulates the activity state of the human BCKD complex and human BCAT isoenzymes. To design the primers for the polymerase chain reaction, human BCKDK was cloned. BCKDK message was found in all human tissues tested, with the highest amount in human muscle. As in rats, there was ubiquitous expression of mitochondrial BCAT, whereas mRNA for the cytosolic enzyme was at or below the limit of detection outside the brain. Finally, the role of BCAA in body nitrogen metabolism is discussed.