Effect of pantethine on the biosynthesis of cholesterol in human skin fibroblasts.
Pantethine [D-bis-(N-pantothenyl-beta-aminoethyl)-disulfide] is a compound used clinically to decrease plasma triglycerides and to increase HDL cholesterol. To understand the mechanism of action of this drug, its effect on the synthesis of cholesterol in cultured skin fibroblasts was assessed. The addition of pantethine (100-200 microM) to cultured cells caused an 80% inhibition in cholesterol synthesis as measured by the incorporation of radiolabeled acetate or mevalonolactone. Inhibition occurred within 4 h of adding the drug and was specific for pantethine; other sulfur-containing compounds such as dithiothreitol, glutathione, coenzyme A and cystine did not inhibit. The inhibition of cholesterol synthesis resulted in the accumulation of radiolabeled methyl sterols. The drug also inhibited total fatty acid synthesis. The amount of [14C]pantethine detected in the cells is very low and represented less than 0.5% of the radiolabeled pantethine added in the medium. At low pantethine concentrations, the drug had negligible effects on the biosynthesis of DNA, protein and phospholipid.
D000085:Acetates / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis; D003864:Depression, Chemical; D005227:Fatty Acids / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007810:Lanosterol / Q000032:analysis; D008798:Mevalonic Acid / Q000378:metabolism; D010204:Pantetheine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012867:Skin / Q000166:cytology; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D000085:Acetates; D005227:Fatty Acids; D013438:Sulfhydryl Compounds; D007810:Lanosterol; D010204:Pantetheine; C005425:pantethine; D004247:DNA; D002784:Cholesterol; D008798:Mevalonic Acid