文章：

癌症中的乙酰辅酶A代谢

Acetyl-CoA metabolism in cancer

原文发布日期：2023-01-19

DOI: 10.1038/s41568-022-00543-5

类型: Review Article

开放获取: 否

英文摘要：

Few metabolites can claim a more central and versatile role in cell metabolism than acetyl coenzyme A (acetyl-CoA). Acetyl-CoA is produced during nutrient catabolism to fuel the tricarboxylic acid cycle and is the essential building block for fatty acid and isoprenoid biosynthesis. It also functions as a signalling metabolite as the substrate for lysine acetylation reactions, enabling the modulation of protein functions in response to acetyl-CoA availability. Recent years have seen exciting advances in our understanding of acetyl-CoA metabolism in normal physiology and in cancer, buoyed by new mouse models, in vivo stable-isotope tracing approaches and improved methods for measuring acetyl-CoA, including in specific subcellular compartments. Efforts to target acetyl-CoA metabolic enzymes are also advancing, with one therapeutic agent targeting acetyl-CoA synthesis receiving approval from the US Food and Drug Administration. In this Review, we give an overview of the regulation and cancer relevance of major metabolic pathways in which acetyl-CoA participates. We further discuss recent advances in understanding acetyl-CoA metabolism in normal tissues and tumours and the potential for targeting these pathways therapeutically. We conclude with a commentary on emerging nodes of acetyl-CoA metabolism that may impact cancer biology.

摘要翻译： 

很少有代谢物能像乙酰辅酶A（acetyl-CoA）那样在细胞代谢中占据如此核心和多功能的地位。乙酰辅酶A在营养分解代谢过程中产生，为三羧酸循环提供能量，并且是脂肪酸和类异戊二烯生物合成的必需基础物质。它还具有信号代谢物的功能，作为赖氨酸乙酰化反应的底物，能够根据乙酰辅酶A的可用性调节蛋白质功能。近年来，借助新的小鼠模型、体内稳定同位素示踪技术以及改进的乙酰辅酶A测量方法（包括在特定亚细胞区室中的测量），我们对正常生理和癌症中乙酰辅酶A代谢的理解取得了激动人心的进展。针对乙酰辅酶A代谢酶的治疗研究也在推进，其中一种靶向乙酰辅酶A合成的治疗剂已获得美国食品和药物管理局的批准。在本篇综述中，我们概述了乙酰辅酶A参与的主要代谢途径的调控及其与癌症的相关性。我们进一步讨论了正常组织和肿瘤中乙酰辅酶A代谢的最新研究进展，以及靶向这些通路进行治疗的潜力。最后，我们对可能影响癌症生物学的乙酰辅酶A代谢新兴节点进行了评述。

原文链接：

Acetyl-CoA metabolism in cancer