支链氨基酸代谢及其与疾病的关系

Branched Chain Amino Acid Metabolism and Its Relationship with Diseases

亮氨酸、异亮氨酸和缬氨酸的疏水侧链都具有分支的甲基基团,因而被统称为支链氨基酸(branched chain amino acids,BCAAs)。作为机体的必需氨基酸,除了作为蛋白质合成的基本原料,BCAAs及其各种分解代谢产物还可以作为信号分子,调控从蛋白质合成到胰岛素分泌等众多生理过程。因此,它们的正常代谢对机体生命活动至关重要。越来越多的证据表明,BCAAs代谢异常与多种疾病关系密切,包括枫糖尿病、神经系统疾病、糖尿病、心血管疾病、肝疾病和癌症等。本文详细概述了哺乳动物中BCAAs分解代谢的基本模式、调控机制(主要关注对2个关键代谢酶BCAT和BCKDH的调控)以及BCAAs参与mTOR和AMPK信号通路在机体代谢中发挥的作用。总结了BCAAs代谢异常与多种疾病的关系,并对有关的矛盾观点进行阐述和解释。近年来,BCAAs代谢及调控在疾病发生发展中的作用成为研究热点,为相关疾病预防和治疗提供了新视角。本综述将为进一步研究提供线索。

Leucine,isoleucine and valine,are referred to as branched chain amino acids(BCAAs) for their hydrophobic side chains with branched methyl groups.As essential amino acids,in addition to being the raw material of protein synthesis,BCAAs and various catabolic products act as signaling molecules,regulating biological processes ranging from protein synthesis to insulin secretion.Therefore,the normal metabolism of BCAAs is crucial to cellular activities.Accumulating evidence demonstrates that the dysregulation of BCAA metabolism is closely related to numerous diseases,including the maple syrup urine disease,nervous system disease,diabetes,cardiovascular disease,liver disease and cancer.Here,we review the regulatory mechanisms of BCAA catabolism in mammals,mainly focusing on the regulation of two key metabolic enzymes(BCAT and BCKDH),and summarize the role of BCAAs in mTOR and AMPK signaling pathways.Furthermore,we also summarize the relationship of abnormal BCAA metabolism with many diseases and expound some contradictory views.In recent years,the role of BCAA metabolism and regulation in the development of diseases has gradually become a hot spot,providing a new perspective for the disease prevention and treatment,and we hope to provide a basis for further reseach.