Longevity & AgingYeast Study Cracks the Code on How Cells Import Key CoA Building Blocks
Coenzyme A (CoA) is essential for energy metabolism, fatty acid synthesis, and hundreds of enzymatic reactions. The canonical pathway begins with vitamin B5 (pantothenate), but alternative routes using pantetheine (PanSH) and 4′-phosphopantetheine (PPanSH) have long been suspected. Until now, how these molecules cross cell membranes was unknown. Using pantothenate-auxotrophic yeast strains, researchers discovered that PanSH and PPanSH spontaneously form mixed disulfides with glutathione (GSH) in the extracellular environment. These mixed disulfides are then imported into cells by the oligopeptide transporter Opt1. Once inside, the CoA precursors are converted to CoA independently of several canonical pathway enzymes—including pantothenate kinase (PANK). The findings define a non-canonical CoA biosynthesis route relevant to human diseases caused by mutations in CoA pathway genes.
