Regulation of acetyl-CoA carboxylase
Regulation of acetyl-CoA carboxylase
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DOI：
10.1042/bst0340223
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发表时间：
2006-04-01
影响因子：
3.9
通讯作者：
Lee, WM
中科院分区：
文献类型：
--
作者：
Brownsey, RW;Boone, AN;Lee, WM
乙酰辅酶A羧化酶（ACC）催化丙二酰辅酶A的形成，丙二酰辅酶A是脂肪生成组织中脂肪酸合成的必需底物，也是肌肉、脑和其他组织中的关键调节分子。ACC对能量代谢的整体控制有重要贡献，并为探索酶控制和激素作用机制提供了重要模型。哺乳动物ACC是多功能二聚体蛋白（530-560 kDa），具有进一步降解和参与多蛋白复合物的潜力。ACC的酶学性质是复杂的，特别是考虑到两个活性位点，必需的催化生物素，三底物反应和变构配体的影响。哺乳动物ACC的两种主要异构体和剪接变体的表达是组织特异性的，并且对激素和营养状况有反应。关键调控元件和同源转录因子仍在定义中。ACC比活性也被迅速调节，响应于胰岛素而增加，并且在细胞暴露于分解代谢激素或环境应激后降低。ACC活性的急性控制是底物供应、变构配体、多个丝氨酸残基的磷酸化以及与其他蛋白质相互作用的综合变化的产物。本文回顾了20世纪70年代末在布里斯托与迪克丹顿一起发起的研究的路径和影响，一直到目前的蛋白质组学和其他方法，这些方法一直具有挑战性和巨大的回报。
Acetyl-CoA carboxylase (ACC) catalyses the formation of malonyl-CoA, an essential substrate for fatty acid synthesis in lipogenic tissues and a key regulatory molecule in muscle, brain and other tissues. ACC contributes importantly to the overall control of energy metabolism and has provided an important model to explore mechanisms of enzyme control and hormone action. Mammalian ACCs are multifunctional dimeric proteins (530-560 kDa) with the potential to further polymerize and engage in multiprotein complexes. The enzymatic properties of ACC are complex, especially considering the two active sites, essential catalytic biotin, the three-substrate reaction and effects of allosteric ligands. The expression of the two major isoforms and splice variants of mammalian ACC is tissue-specific and responsive to hormones and nutritional status. Key regulatory elements and cognate transcription factors are still being defined. ACC specific activity is also rapidly modulated, being increased in response to insulin and decreased following exposure of cells to catabolic hormones or environmental stress. The acute control of ACC activity is the product of integrated changes in substrate supply, allosteric ligands, the phosphorylation of multiple serine residues and interactions with other proteins. This review traces the path and implications of studies initiated with Dick Denton in Bristol in the late 1970s, through to current proteomic and other approaches that have been consistently challenging and immensely rewarding.