Theodoulou Frederica L, Sibon Ody C M, Jackowski Suzanne, Gout Ivan
*Biological Chemistry and Crop Protection Department, Rothamsted Research, Harpenden AL5 2JQ, U.K.
†Department of Cell Biology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Biochem Soc Trans. 2014 Aug;42(4):1025-32. doi: 10.1042/BST20140176.
In 1945, Fritz Lipmann discovered a heat-stable cofactor required for many enzyme-catalysed acetylation reactions. He later determined the structure for this acetylation coenzyme, or coenzyme A (CoA), an achievement for which he was awarded the Nobel Prize in 1953. CoA is now firmly embedded in the literature, and in students' minds, as an acyl carrier in metabolic reactions. However, recent research has revealed diverse and important roles for CoA above and beyond intermediary metabolism. As well as participating in direct post-translational regulation of metabolic pathways by protein acetylation, CoA modulates the epigenome via acetylation of histones. The organization of CoA biosynthetic enzymes into multiprotein complexes with different partners also points to close linkages between the CoA pool and multiple signalling pathways. Dysregulation of CoA biosynthesis or CoA thioester homoeostasis is associated with various human pathologies and, although the biochemistry of CoA biosynthesis is highly conserved, there are significant sequence and structural differences between microbial and human biosynthetic enzymes. Therefore the CoA biosynthetic pathway is an attractive target for drug discovery. The purpose of the Coenzyme A and Its Derivatives in Cellular Metabolism and Disease Biochemical Society Focused Meeting was to bring together researchers from around the world to discuss the most recent advances on the influence of CoA, its biosynthetic enzymes and its thioesters in cellular metabolism and diseases and to discuss challenges and opportunities for the future.
1945年，弗里茨·利普曼发现了许多酶催化乙酰化反应所需的一种热稳定辅因子。他后来确定了这种乙酰化辅酶即辅酶A（CoA）的结构，他也因此成就于1953年被授予诺贝尔奖。如今，CoA作为代谢反应中的酰基载体，已稳固地扎根于文献以及学生们的认知之中。然而，最近的研究揭示了CoA在中间代谢之外的多种重要作用。除了通过蛋白质乙酰化参与代谢途径的直接翻译后调控外，CoA还通过组蛋白乙酰化调节表观基因组。CoA生物合成酶与不同伙伴形成多蛋白复合物的组织方式也表明CoA库与多种信号通路之间存在紧密联系。CoA生物合成或CoA硫酯稳态的失调与多种人类疾病相关，尽管CoA生物合成的生物化学过程高度保守，但微生物和人类生物合成酶之间存在显著的序列和结构差异。因此，CoA生物合成途径是药物研发的一个有吸引力的靶点。“辅酶A及其衍生物在细胞代谢和疾病中的作用”生物化学会聚焦会议的目的是汇聚世界各地的研究人员，讨论CoA及其生物合成酶和硫酯在细胞代谢和疾病中的影响的最新进展，并探讨未来的挑战和机遇。
