Figure 1

CoA metabolism. CoA de novo biosynthesis. Vitamin B5, or pantothenate, is taken up and intracellularly converted to CoA sequentially by the enzymes PANK, PPCS, PPCDC, COASY (PPAT and DPCK). Order and abbreviations of starting, intermediate and end products (Pan, P-Pan, P-PantSH, dPCoASH and CoASH) are provided on the left. Several salvage pathways to this route exist. Externally provided CoA can be converted into P-PantSH, which can be taken up by cells and intracellularly converted to CoA²⁹. Externally provided PantSH can rescue a CoA-depleted phenotype^{18, 31} via unknown mechanisms including a possible ‘kinase X’ that phosphorylates PantSH to form P-PantSH. Pant-SS-Pant can be converted into PantSH. PantSH can be degraded into Pan and cysteamine by pantetheinases or vanins. PANK = pantothenate kinase; PPCS = phosphopantothenoylcysteine synthetase; PPCDC = phosphopanthenoylcysteine-decarboxylase; PPAT = phosphopantetheine adenylyltransferase; PPCK = dephospho-CoA kinase. Pan = pantothenate; P-Pan = 4′-phosphopantothenate; Pant-SS-Pant = pantethine; PantSH = pantetheine; P-PantSH = 4′-phosphopantetheine; dPCoASH = dephosphoCoA; CoASH = Coenzyme A.