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).

三羧酸循环、营养物氧化、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 CoA 所携带的酰基在这些过程中的来源和调控得到了深入研究，但一个关键的根本问题却很少被考虑：CoA 本身的生产是如何控制的？在这里，我们讨论了 CoA 的许多细胞作用以及控制其从半胱氨酸、ATP 和必需营养素泛酸（维生素 B ₅ ）或从哺乳动物中回收的前体进行生物合成的调节机制。涉及乙酰辅酶A、其他酰基辅酶A、酰基肉碱、MYC、p53、PPARα、PINK1 和胰岛素和生长因子刺激的 PI3K–AKT 信号传导的代谢反馈和信号传导机制调节维生素 B ₅转运蛋白 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、针对 CoA 生物合成的化合物以及途径酶突变引起的疾病的方法，包括白内障、心肌病和神经变性（PKAN 和 COPAN）的类型。