Rana Sandeep, Blowers Elizabeth C, Natarajan Amarnath
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center , Omaha, Nebraska 68198-6805, United States.
J Med Chem. 2015 Jan 8;58(1):2-29. doi: 10.1021/jm401994c. Epub 2014 Aug 28.
Adenosine 5'-monophosphate activated protein kinase (AMPK) is a master sensor of cellular energy status that plays a key role in the regulation of whole-body energy homeostasis. AMPK is a serine/threonine kinase that is activated by upstream kinases LKB1, CaMKKβ, and Tak1, among others. AMPK exists as αβγ trimeric complexes that are allosterically regulated by AMP, ADP, and ATP. Dysregulation of AMPK has been implicated in a number of metabolic diseases including type 2 diabetes mellitus and obesity. Recent studies have associated roles of AMPK with the development of cancer and neurological disorders, making it a potential therapeutic target to treat human diseases. This review focuses on the structure and function of AMPK, its role in human diseases, and its direct substrates and provides a brief synopsis of key AMPK modulators and their relevance in human diseases.
5'-单磷酸腺苷激活蛋白激酶(AMPK)是细胞能量状态的主要传感器,在全身能量稳态调节中起关键作用。AMPK是一种丝氨酸/苏氨酸激酶,可被上游激酶LKB1、CaMKKβ和Tak1等激活。AMPK以αβγ三聚体复合物形式存在,受AMP、ADP和ATP变构调节。AMPK失调与包括2型糖尿病和肥胖症在内的多种代谢性疾病有关。最近的研究将AMPK的作用与癌症和神经系统疾病的发展联系起来,使其成为治疗人类疾病的潜在治疗靶点。本综述重点介绍了AMPK的结构和功能、其在人类疾病中的作用及其直接底物,并简要概述了关键的AMPK调节剂及其与人类疾病的相关性。