PANK2-mediated <i>de novo</i> CoA synthesis is required for metabolic switching to fatty acid oxidation.

ABSTRACT: Humans have 3 different PANK enzymes (PANK1-3) that catalyze the first step in the de novo synthesis of Coenzyme A (CoA). All PANKs are feedback inhibited by acyl-CoAs but only PANK2 can overcome this inhibition by binding palmitoyl-carnitine. Previous studies, conducted under glucose-replete conditions, have failed to detect a PANK2-mediated contribution to CoA synthesis. We found that exposure to BSA-conjugated palmitate (PAL-BSA) led to activation of fatty acid oxidation (FAO) and the accumulation of both palmitoyl-carnitine and palmitoyl-CoA in HEK293T cells, suggesting that PANK2 is active under these conditions. Isotope tracing experiments with ¹³C¹⁵N-pantothenate showed that PANK2 uniquely sustains de novo CoA synthesis and high production of Acet

SUBMITTER: Nordlie SM 

PROVIDER: S-EPMC12632504 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature