摘要
近年来,酮体代谢在肿瘤生长、侵袭、转移过程中的作用备受关注。琥珀酰辅酶A转移酶(SCOT)是酮体代谢的关键酶。其作用是将琥珀酰辅酶A的辅酶A基团转移至乙酰乙酸从而催化乙酰乙酰辅酶A的形成,是酮体代谢的第一个限速步骤,随后乙酰乙酰辅酶A进一步断裂成两分子的乙酰辅酶A进入三羧酸循环。研究表明SCOT在多种肿瘤中显著高表达,与肿瘤进展及患者预后密切相关,这使SCOT可作为临床诊断及预后评估的潜在标志物;另外,抑制SCOT活性可使肿瘤细胞酮体代谢受阻,即减少ATP产生,进而抑制肿瘤生长、增殖、侵袭与转移。探讨SCOT在代谢途径中的重要作用以及与肿瘤发生发展的关系,为发掘肿瘤代谢靶向分子药物提供新的思路。
In recent years,the role of ketone body metabolism in tumor growth,invasion and metastasis has attracted much attention.Succinyl-CoA transferase(SCOT)is a key enzyme in the metabolism of ketone bodies.Its function is to transfer the coenzyme A group of succinyl-CoA to acetoacetate and catalyze the formation of acetoacetyl-CoA,which is the first rate-limiting step in ketone metabolism.Then acetoacetyl-CoA further breaks into two molecules of acetyl-CoA and enters the tricarboxylic acid cycle.Studies have shown that SCOT is highly expressed in a variety of tumors,and is closely related to tumor progression and prognosis of patients,which makes SCOT a potential marker for clinical diagnosis and prognosis evaluation;in addition,inhibition of SCOT activity can hinder the metabolism of ketone bodies in tumor cells,that is,reduce the production of ATP,thereby inhibiting tumor growth,proliferation,invasion and metastasis.This review aims to explore the important role of SCOT in metabolic pathways and its relationship with tumorigenesis and development,and to provide new ideas for exploring tumor metabolism and targeting molecular drugs.
作者
张智慧
王庆华
季鸣
陈晓光
ZHANG Zhi-hui;WANG Qing-hua;JI Ming;CHEN Xiao-guang(State Key Laboratory of Bioactive Substances and Functions of Natural Medicines/Beijing Key Laboratory of Non-clinical Drug Metabolism and PK/PD Study,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)
出处
《药学学报》
CAS
CSCD
北大核心
2019年第10期1831-1836,共6页
Acta Pharmaceutica Sinica
基金
“十三五”国家“重大新药创制”科技重大专项(2018ZX09711001-003)
关键词
酮体
酮解
琥珀酰辅酶A转移酶
肿瘤
ketone body
ketolysis
succinyl-CoA transferase
tumor
作者简介
通讯作者:陈晓光,Tel:86-10-63165207,E-mail:chxg@imm.ac.cn
