pantetheine and phosphopantothenic-acid

Preincubation of Ehrlich ascites tumor cells at 22 or 32 degrees C, but not at 0 degree C, with pantothenic acid, 4'-phosphopantothenic acid, pantothenol, or pantethine reduced lipid peroxidation (measured by production of thiobarbituric acid-reactive compounds) induced by the Fenton reaction (Fe2+ + H2O2) and partly protected the plasma membrane against the leakiness to cytoplasmic proteins produced by the same reagent. Pantothenic acid and its derivatives did not inhibit (Fe2+ + H2O2)-induced peroxidation of phospholipid multilamellar vesicles, thus indicating that their effect on the cells was not due to the scavenging mechanism. Homopantothenic acid and its 4'-phosphate ester (which are not precursors of CoA) neither protected Ehrlich ascites tumor cells against lipid peroxidation nor prevented plasma membrane leakiness under the same conditions. Incubation of the cells with pantothenic acid, 4'-phosphopantothenic acid, pantothenol, or pantethine significantly increased the amount of cellular CoA and potentiated incorporation of added palmitate into phospholipids and cholesterol esters. It is concluded that pantothenic acid and its related compounds protect the plasma membrane of Ehrlich ascites tumor cells against the damage by oxygen free radicals due to increasing cellular level of CoA. The latter compound may act by diminishing propagation of lipid peroxidation and promoting repair mechanisms, mainly the synthesis of phospholipids.

Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Membrane; Coenzyme A; Fatty Acids; Female; Ferrous Compounds; Hydrogen Peroxide; Lipid Peroxidation; Mice; Palmitic Acid; Palmitic Acids; Pantetheine; Pantothenic Acid; Thiobarbituric Acid Reactive Substances

Coenzyme A (CoA) and acyl carrier protein are two cofactors in fatty acid metabolism, and both possess a 4'-phosphopantetheine moiety that is metabolically derived from the vitamin pantothenate. We studied the regulation of the metabolic pathway that gives rise to these two cofactors in an Escherichia coli beta-alanine auxotroph, strain SJ16. Identification and quantitation of the intracellular and extracellular beta-alanine-derived metabolites from cells grown on increasing beta-alanine concentrations were performed. The intracellular content of acyl carrier protein was relatively insensitive to beta-alanine input, whereas the CoA content increased as a function of external beta-alanine concentration, reaching a maximum at 8 microM beta-alanine. Further increase in the beta-alanine concentration led to the excretion of pantothenate into the medium. Comparing the amount of pantothenate found outside the cell to the level of intracellular metabolites demonstrates that E. coli is capable of producing 15-fold more pantoic acid than is required to maintain the intracellular CoA content. Therefore, the supply of pantoic acid is not a limiting factor in CoA biosynthesis. Wild-type cells also excreted pantothenate into the medium, showing that the beta-alanine supply is also not rate limiting in CoA biogenesis. Taken together, the results point to pantothenate kinase as the primary enzymatic step that regulates the CoA content of E. coli.

Topics: Acyl Carrier Protein; beta-Alanine; Coenzyme A; Escherichia coli; Organophosphorus Compounds; Pantetheine; Pantothenic Acid

Non-proliferating cells of Lactobacillus plantarum accumulated about 1.3 mug of pantothenic acid (PA) per milligram dry cells when placed in a phosphate-buffered solution containing glucose, NaCl, and PA for 21 h. Under the conditions applied for PA uptake, pH 7.5 and 38 degrees C, the accumulated PA existed almost exclusively in a bound form. Free PA was observed only occasionally and then at questionably significant levels. All bound PA was released quantitatively by enzyme hydrolysis with alkaline (intestinal) phosphatase. Chromatographic analysis coupled with differential microbiological analysis of cell extracts using Saccharomyces cerevisiae, Lactobacillus helveticus, and L. plantarum identified the accumulated PA as phosphopantothenic acid (P-PA). Assay of P-PA loaded cell extracts (devoid of free PA) by L. plantarum before and after alkaline phosphatase hydrolysis showed that the growth of this primary assay organism was stimulated by 8.3%.

Topics: Alkaline Phosphatase; Cell-Free System; Hydrolysis; Lactobacillus; Pantetheine; Pantothenic Acid; Saccharomyces