Inhibition of acetyl-CoA carboxylase by cystamine may mediate the hypotriglyceridemic activity of pantethine.
Pantethine is a versatile and well-tolerated hypolipidemic agent whose efficacy in this regard appears to be mediated by its catabolic product cystamine, a nucleophile which avidly attacks disulfide groups. An overview of pantethine research suggests that the hypotriglyceridemic activity of pantethine reflects cystamine-mediated inhibition of the hepatic acetyl-CoA carboxylase, which can be expected to activate hepatic fatty acid oxidation. Inhibition of HMG-CoA reductase as well as a more distal enzyme in the cholesterol synthetic pathway may account for pantethine's hypocholesterolemic effects. If pantethine does indeed effectively inhibit hepatic acetyl-CoA carboxylase, it may have adjuvant utility in the hepatothermic therapy of obesity. As a safe and effective compound of natural origin, pantethine merits broader use in the management of hyperlipidemias.
McCarty
M F
MF
Pantox Laboratories, San Diego, CA 92109, USA.
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D003538:Cystamine / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009765:Obesity / Q000188:drug therapy; D010204:Pantetheine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism*
D005227:Fatty Acids; D000960:Hypolipidemic Agents; D014280:Triglycerides; D010204:Pantetheine; C005425:pantethine; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D000103:Acetyl-CoA Carboxylase; D003538:Cystamine