Mitochondrial metabolism of 3-mercaptopropionic acid. Chemical synthesis of 3-mercaptopropionyl coenzyme A and some of its S-acyl derivatives.
The metabolism of 3-mercaptopropionic acid in mitochondria was studied by use of purified mitochondrial enzymes and rat heart mitochondria. Metabolites of 3-mercaptopropionic acid were separated by high performance liquid chromatography and identified by comparing them with chemically synthesized derivatives of 3-mercaptopropionic acid. The initial step in the metabolism of 3-mercaptopropionic acid is its conversion to a CoA thioester, most likely catalyzed by medium-chain acyl-CoA synthetase. The resulting 3-mercaptopropionyl-CoA is a poor substrate of acyl-CoA dehydrogenase but substitutes effectively for CoASH in reactions catalyzed by 3-ketoacyl-CoA thiolase and acetoacetyl-CoA thiolase. S-Acyl-3-mercaptopropionyl-CoA thioesters formed in the thiolase-catalyzed reactions are not at all or only poorly acted upon by acyl-CoA dehydrogenases. However, they are hydrolyzed by thioesterase(s) to CoASH and S-acyl-3-mercaptopropionic acid. The hydrolysis of S-acyl-3-mercaptopropionyl-CoA thioesters proceeds more rapidly than the hydrolysis of fatty acyl-CoA thioesters of comparable chain lengths. Free CoASH is also regenerated from S-acetyl-3-mercaptopropionyl-CoA and more rapidly from 3-mercaptopropionyl-CoA as a result of their reactions with carnitine catalyzed by carnitine acetyltransferase. These findings lead to the suggestion that the major mitochondrial CoA-containing metabolites of 3-mercaptopropionic acid are S-acyl-3-mercaptopropionyl-CoA thioesters.
D015097:3-Mercaptopropionic Acid / Q000378:metabolism*; D000102:Acetyl-CoA C-Acyltransferase / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000138:chemical synthesis* / Q000378:metabolism; D044944:Acyl-CoA Dehydrogenases / Q000378:metabolism; D000818:Animals; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism; D007202:Indicators and Reagents; D008929:Mitochondria, Heart / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds
C045680:3-mercaptopropionyl-coenzyme A; D000214:Acyl Coenzyme A; D007202:Indicators and Reagents; D013438:Sulfhydryl Compounds; D015097:3-Mercaptopropionic Acid; D044944:Acyl-CoA Dehydrogenases; D000102:Acetyl-CoA C-Acyltransferase; D002332:Carnitine O-Acetyltransferase; D003066:Coenzyme A Ligases