Extracellular 4'-phosphopantetheine is a source for intracellular coenzyme A synthesis.

The metabolic cofactor coenzyme A (CoA) gained renewed attention because of its roles in neurodegeneration, protein acetylation, autophagy and signal transduction. The long-standing dogma is that eukaryotic cells obtain CoA exclusively via the uptake of extracellular precursors, especially vitamin B5, which is intracellularly converted through five conserved enzymatic reactions into CoA. This study demonstrates an alternative mechanism that allows cells and organisms to adjust intracellular CoA levels by using exogenous CoA. Here CoA was hydrolyzed extracellularly by ectonucleotide pyrophosphatases to 4'-phosphopantetheine, a biologically stable molecule able to translocate through membranes via passive diffusion. Inside the cell, 4'-phosphopantetheine was enzymatically converted back to CoA by the bifunctional enzyme CoA synthase. Phenotypes induced by intracellular CoA deprivation were reversed when exogenous CoA was provided. Our findings answer long-standing questions in fundamental cell biology and have major implications for the understanding of CoA-related diseases and therapies.

D-pantethine has vitamin activity equivalent to d-pantothenic acids for recovering from a deficiency of D-pantothenic acid in rats.

D-Pantethine is a compound in which two molecules of D-pantetheine bind through an S-S linkage. D-Pantethine is available from commercial sources as well as from D-pantothenic acid. We investigated if D-pantethine has the same vitamin activity as D-pantothenic acid by comparing the recovery from a deficiency of D-pantothenic acid in rats. D-Pantothenic acid-deficient rats were developed by weaning rats on a diet lacking D-pantothenic acid for 47 d. At that time, the urinary excretion of D-pantothenic acid was almost zero, and the body weight extremely low, compared with the control (p<0.05); the contents of free D-pantothenic acid were also significantly reduced in comparison with those of controls (p<0.05). D-Pantothenic acid-deficient rats were administered a diet containing D-pantothenic acid or D-pantethine for 7 d. D-Pantethine and D-pantothenic acid contents of the diets were equimolar in forms of D-pantothenic acid. We compared various parameters concerning nutritional status between rats fed D-pantothenic acid- and D-pantethine-containing diets. The recoveries of body weight, tissue weights, and tissue concentrations of free D-pantothenic acid, dephospho-CoA, CoA, and acetyl-CoA were identical between rats fed diets containing D-pantothenic acid and D-pantethine. Thus, the biological efficiency for recovering from a deficiency of D-pantothenic acid in rats was equivalent between D-pantothenic acid and D-pantethine.