AMPK:细胞能量中枢

腺苷酸活化蛋白激酶(AMPactivated proteinkinase,AMPK)是真核细胞中高度保守的丝氨酸/苏氨酸蛋白激酶,以异源三聚体的形式广泛存在于真核生物体内,是细胞的能量感受器,在能量代谢调控中起极其重要的作用。肝激酶B1(LKB1)、Ca2+/CaM-依赖蛋白激酶激酶β(CaMKKβ)、AMP/ATP或ADP/ATP比值升高以及诸如运动肌肉收缩等生理刺激均可以激活AMPK,进而调节细胞的能量代谢网络,提高其应对内外环境变化的能力,从而维持细胞水平乃至整个机体的稳定状态。活化的AMPK可以增强分解代谢,抑制合成代谢,上调ATP水平,参与细胞糖代谢、脂肪代谢、蛋白质代谢等能量代谢过程,增加细胞能量储备,应对能量缺乏。同时活化的AMPK参与细胞的生长、增殖、凋亡、自噬等基本生物学过程。AMPK是研究肥胖,糖尿病等能量代谢性疾病的核心。肿瘤细胞存在特殊的能量代谢方式,其发生,生长,转移与能量代谢失衡密切相关。AMPK与肿瘤细胞异常的能量代谢相关,为肿瘤发生、发展机制研究提供新的策略。本文主要探讨AMPK的结构、激活机制、参与的物质能量代谢和细胞的基本生物学过程以及与肿瘤发生的关联。

AMPK: Celluar Energy Centre

AMP activated protein kinase (AMPK) is a highly conserved Ser/Thr protein kinase in eukaryotic cells, in which the kinase exists in a shape of heterotrimer. It is an essential cellular energy sensor, which plays an important role in the regulation of energy metabolism. Liver Kinase B1( LKB1), Ca2+/CaM-dependent protein kinase-beta(CaMKK-beta), the increasing ratio of AMP/ATP or ADP/ATP, and other physiological stimulations such as exercise, muscle contraction which can activate AMPK, regulate cellular energy metabolism and facilitate to adapt to nutrient stress, so the cell and whole body homeostasis can be assured. Activation of AMPK can increase the level of ATP by enhancing catabolism and inhibiting constructive metabolism, involving in glycometabolism, lipidmetabolism and proteometabolism, increasing the energy reserve, which can deal well with the energy deficiency. AMPK is also involved in cell growth, proliferation, apoptosis, autophagy and other basic biological processes. AMPK is a core point to study the metabolic diseases including diabetes mellitus and obesity. Imbalanced energy metabolism is associated with tumorigenesis, progression and metastasis. AMPK plays a role in linking metabolic syndrome and cancer, providing a new strategy for the study of cancerous occurrence and development mechanism. This paper will focus on the cellular energy central function of AMPK and the relationship with cancer.