Samuel A. Barritt, Sarah E. DuBois-Coyne, Christian C. Dibble
{"title":"Coenzyme A biosynthesis: mechanisms of regulation, function and disease","authors":"Samuel A. Barritt, Sarah E. DuBois-Coyne, Christian C. Dibble","doi":"10.1038/s42255-024-01059-y","DOIUrl":null,"url":null,"abstract":"The tricarboxylic acid cycle, nutrient oxidation, histone acetylation and synthesis of lipids, glycans and haem all require the cofactor coenzyme A (CoA). Although the sources and regulation of the acyl groups carried by CoA for these processes are heavily studied, a key underlying question is less often considered: how is production of CoA itself controlled? Here, we discuss the many cellular roles of CoA and the regulatory mechanisms that govern its biosynthesis from cysteine, ATP and the essential nutrient pantothenate (vitamin B5), or from salvaged precursors in mammals. Metabolite feedback and signalling mechanisms involving acetyl-CoA, other acyl-CoAs, acyl-carnitines, MYC, p53, PPARα, PINK1 and insulin- and growth factor-stimulated PI3K–AKT signalling regulate the vitamin B5 transporter SLC5A6/SMVT and CoA biosynthesis enzymes PANK1, PANK2, PANK3, PANK4 and COASY. We also discuss methods for measuring CoA-related metabolites, compounds that target CoA biosynthesis and diseases caused by mutations in pathway enzymes including types of cataracts, cardiomyopathy and neurodegeneration (PKAN and COPAN). This Review summarizes the fundamental aspects related to coenzyme A synthesis and its implications as a central molecule in metabolism.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":18.9000,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature metabolism","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s42255-024-01059-y","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
The tricarboxylic acid cycle, nutrient oxidation, histone acetylation and synthesis of lipids, glycans and haem all require the cofactor coenzyme A (CoA). Although the sources and regulation of the acyl groups carried by CoA for these processes are heavily studied, a key underlying question is less often considered: how is production of CoA itself controlled? Here, we discuss the many cellular roles of CoA and the regulatory mechanisms that govern its biosynthesis from cysteine, ATP and the essential nutrient pantothenate (vitamin B5), or from salvaged precursors in mammals. Metabolite feedback and signalling mechanisms involving acetyl-CoA, other acyl-CoAs, acyl-carnitines, MYC, p53, PPARα, PINK1 and insulin- and growth factor-stimulated PI3K–AKT signalling regulate the vitamin B5 transporter SLC5A6/SMVT and CoA biosynthesis enzymes PANK1, PANK2, PANK3, PANK4 and COASY. We also discuss methods for measuring CoA-related metabolites, compounds that target CoA biosynthesis and diseases caused by mutations in pathway enzymes including types of cataracts, cardiomyopathy and neurodegeneration (PKAN and COPAN). This Review summarizes the fundamental aspects related to coenzyme A synthesis and its implications as a central molecule in metabolism.
三羧酸循环、营养物质氧化、组蛋白乙酰化以及脂质、聚糖和血红素的合成都需要辅因子辅酶 A(CoA)。尽管人们对 CoA 所携带的酰基在这些过程中的来源和调控进行了大量研究,但却较少考虑一个关键的基本问题:如何控制 CoA 本身的产生?在这里,我们将讨论 CoA 在细胞中的多种作用,以及在哺乳动物体内从半胱氨酸、ATP 和必需营养素泛酸(维生素 B5)或从残余前体中生物合成 CoA 的调控机制。代谢物反馈和信号机制涉及乙酰-CoA、其他酰基-CoAs、酰基肉碱、MYC、p53、PPARα、PINK1 以及胰岛素和生长因子刺激的 PI3K-AKT 信号,它们调节维生素 B5 转运体 SLC5A6/SMVT 和 CoA 生物合成酶 PANK1、PANK2、PANK3、PANK4 和 COASY。我们还讨论了测量 CoA 相关代谢物的方法、靶向 CoA 生物合成的化合物以及由途径酶突变引起的疾病,包括白内障、心肌病和神经变性(PKAN 和 COPAN)。
期刊介绍:
Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.