Harris Robert A, Joshi Mandar, Jeoung Nam Ho, Obayashi Mariko
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, 46202, USA.
J Nutr. 2005 Jun;135(6 Suppl):1527S-30S. doi: 10.1093/jn/135.6.1527S.
The branched-chain amino acids (BCAAs) are required for protein synthesis and neurotransmitter synthesis. The branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) is the most important regulatory enzyme in the catabolic pathways of the BCAAs. Activity of the complex is controlled by covalent modification with phosphorylation of its branched-chain alpha-ketoacid dehydrogenase subunits by a specific kinase [branched-chain kinase (BDK)] causing inactivation and dephosphorylation by a specific phosphatase [branched-chain phosphatase (BDP)] causing activation. Tight control of BCKDC activity is important for conserving as well as disposing of BCAAs. Phosphorylation of the complex occurs when there is a need to conserve BCAAs for protein synthesis; dephosphorylation occurs when BCAAs are present in excess. The relative activities of BDK and BDP set the activity state of BCKDC. BDK activity is regulated by alpha-ketoisocaproate inhibition and altered level of expression. Less is known about BDP but a novel mitochondrial phosphatase was identified recently that may contribute to the regulation of BCKDC. Reduced capacity to oxidize BCAAs, as in maple syrup urine disease, results in excess BCAAs in the blood and profound neurological dysfunction and brain damage. In contrast, loss of control of BCAA oxidation results in growth impairment and epileptic-like seizures. These findings emphasize the importance of control of BCAA catabolism for normal neurological function. It is proposed that the safe upper limit of dietary BCAA intake could be established with a BCAA tolerance test and clamp protocol.
支链氨基酸（BCAAs）是蛋白质合成和神经递质合成所必需的。支链α-酮酸脱氢酶复合体（BCKDC）是BCAAs分解代谢途径中最重要的调节酶。该复合体的活性通过其支链α-酮酸脱氢酶亚基被特定激酶[支链激酶（BDK）]磷酸化的共价修饰来控制，导致失活，以及被特定磷酸酶[支链磷酸酶（BDP）]去磷酸化，导致激活。严格控制BCKDC活性对于BCAAs的保存和代谢都很重要。当需要为蛋白质合成保存BCAAs时，复合体会发生磷酸化；当BCAAs过量存在时，会发生去磷酸化。BDK和BDP的相对活性决定了BCKDC的活性状态。BDK活性受α-酮异己酸抑制和表达水平改变的调节。关于BDP的了解较少，但最近鉴定出一种新的线粒体磷酸酶，可能有助于BCKDC的调节。如枫糖尿症那样，氧化BCAAs的能力降低会导致血液中BCAAs过量，并导致严重的神经功能障碍和脑损伤。相反，BCAA氧化控制丧失会导致生长障碍和癫痫样发作。这些发现强调了控制BCAA分解代谢对正常神经功能的重要性。有人提出，可以通过BCAA耐受试验和钳夹方案来确定饮食中BCAA摄入的安全上限。
