Pantothenate and coenzyme A biosynthesis pathway enzymes (CoA biosynthesis pathway)

The pantothenate and coenzyme A (CoA) biosynthesis pathway is a fundamental metabolic route responsible for the production of CoA, an essential cofactor required for approximately 4% of all known enzymatic reactions, including those in the TCA cycle and fatty acid metabolism (PMID: 30867594). In humans, the pathway involves five enzymatic steps starting from pantothenate (vitamin B5), catalyzed by pantothenate kinase (PanK), phosphopantothenoylcysteine synthetase (PPCS), phosphopantothenoylcysteine decarboxylase (PPCDC), phosphopantetheine adenylyltransferase (PPAT), and dephospho-CoA kinase (DPCK) (UniProt: P82970). This pathway is a critical therapeutic target in infectious diseases, as many pathogens utilize structurally distinct enzymes or unique de novo synthesis steps (e.g., PanC, PanD) that can be selectively inhibited to deplete CoA and kill the organism (PMID: 25104754). Additionally, the pathway is central to the pathology of pantothenate kinase-associated neurodegeneration (PKAN), a rare genetic disorder caused by mutations in the PANK2 gene. Current drug development efforts focus on PanK activators like CAB834 to bypass enzymatic blocks in PKAN, as well as pantothenamides that act as antimetabolites or inhibitors in pathogens such as Plasmodium falciparum and Mycobacterium tuberculosis (PMID: 31112183).

Other names

Coenzyme A biosynthesis pathwayPantothenate kinase pathwayVitamin B5 metabolism pathwayDe novo CoA biosynthesis pathway

Inhibition of microbial enzymes (e.g., PanK, PanC) to deplete Coenzyme A levels in pathogens; Allosteric activation of human pantothenate kinase isoforms to restore CoA levels in genetic deficiency states.