Coenzyme A (CoA) is an essential cofactor in all living organisms. CoA and its thioesters (Acetyl-CoA, Malonyl-CoA, HMG-CoA etc) are implicated in a diverse range of metabolic pathways, such as oxidation of carbohydrates, lipids and proteins, the citric acid cycle, lipid and cholesterol biosynthesis, as well as for covalent modification of proteins and regulation of gene expression. The level of CoA/CoA derivatives is not constant in cells and tissues and changes in response to cellular metabolites, nutrients, diet (e.g. high fat diet), and hormones (insulin, glucagon, glucocorticoids). These changes are important for the metabolic adaptation of cells to different physiological and pathological conditions. Abnormal CoA/CoA derivatives levels have been observed in diverse human pathologies including cancer, metabolic disorders and neurodegeneration. CoA is synthesised in prokaryotic and eukaryotic cells from pantothenate (vitamin B5), ATP and cysteine by a five-step biosynthetic pathway. There are two rate-limiting steps in CoA biosynthesis, involving pantothenate kinase (PANK) and CoA synthase (CoAsy). Our efforts have been mainly focused on elucidating the regulation of CoAsy by signalling pathways and revealing the mechanisms by which the CoA biosynthetic complex is formed in response to extracellular stimuli and stresses. Recent advances on these studies will be presented.
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