Coenzyme A biosynthetic pathway (CoA biosynthesis)

Pantothenic acid (Vitamin B5) is the essential precursor for the synthesis of Coenzyme A (CoA) and Acyl Carrier Protein (ACP), which are vital cofactors in numerous metabolic processes [1, 3]. The pathway involves five enzymatic steps, starting with the phosphorylation of pantothenate by pantothenate kinase (PANK), which is the rate-limiting and primary regulatory step [2, 5]. CoA is crucial for the tricarboxylic acid (TCA) cycle, fatty acid oxidation, and the synthesis of cholesterol, neurotransmitters, and heme [1, 3]. Dysregulation of this pathway, specifically mutations in the PANK2 gene, is the primary cause of Pantothenate Kinase-Associated Neurodegeneration (PKAN), a rare genetic disorder characterized by progressive extrapyramidal dysfunction and iron accumulation in the basal ganglia [4]. In pharmacology, enzymes within this pathway are explored as targets for antimicrobial agents, as many pathogens rely on de novo CoA synthesis, and for treating neurodegenerative diseases through the use of PANK activators or CoA precursors [3, 5].

Other names

Pantothenate metabolismVitamin B5 metabolic pathwayPantothenate and CoA biosynthesisGeneral metabolic enzymes and pathways utilizing pantothenic acid

Modulation of intracellular Coenzyme A levels through the activation or inhibition of pantothenate kinase (PANK) enzymes [2, 5].