Dr. Lipmann isolated coenzyme A (CoA), an activated thiol compound that contains vitamin B₅ (pantothenic acid) as a core component. As acetyl-CoA, CoA participates in the TCA cycle, fatty-acid synthesis, cholesterol formation and many other pathways, acting as a carbon-transfer shuttle. Understanding intermediary metabolism has direct implications for diagnosing nutritional deficiencies and inborn errors of metabolism, and has guided the development of antibiotics and lipid-lowering drugs.

CoA is composed of 3´-phosphoadenosine diphosphate, pantothenic acid and β-mercaptoethylamine; its terminal ‑SH group forms high-energy thioester bonds. Lipmann analyzed ATP-dependent acetate activation in yeast extracts and demonstrated the presence of the activated intermediate “acetyl-CoA.” Acetyl-CoA supplies carbon to ketone-body production, isoprenoid synthesis and histone acetylation, serving as a central node linking metabolic crosstalk to epigenetic regulation. Fluctuations in CoA levels have recently been implicated in oxidative-stress responses and neurodegenerative diseases.

Lipmann’s team combined ATP-PPʹ exchange assays with high-speed paper electrophoresis of activated acetate, showing that excess CoA determined the acetate→acetyl-CoA conversion rate. Sulfur-specific iodoacetate labeling proved thiol dependence, and pantothenate-deficient yeast lacking the reaction suggested a vitamin-dependent cofactor. Mutations in CoA-remodeling enzymes (CoA-synthase, PANK family) are now known to cause neurodegenerative diseases such as PKAN, putting thioester-pool homeostasis at the center of current research.