title: Active-site probes of carnitine acyltransferases. Inhibition of carnitine acetyltransferase by hemiacetylcarnitinium, a reaction intermediate analogue.
abstract: Hemiacetylcarnitinium (2S,6R:2R,65)-6-carboxymethyl-2-hydroxy-2,4,4- trimethylmorpholinium) chloride is a relatively potent competitive inhibitor (Ki = 0.89 mM) of pigeon breast carnitine acetyltransferase (CAT) and of the crude rat liver CAT (Ki = 4.72 mM) but is neither an inhibitor nor an effective substrate for purified rat liver carnitine palmitoyltransferase (CPT). It does not inhibit state 3 oxygen consumption in isolated hepatic mitochondria using palmitoyl-CoA or palmitoylcarnitine as substrates. This compound is a reaction intermediate analogue of the proposed tetrahedral intermediate for acetyl transfer between acetylcarnitine and CoASH. Because the hemiketal carbon is chiral, a suggestion is made that one of the enantiomers has the same relative configuration as the proposed tetrahedral intermediate.
mesh_terms: D000108:Acetylcarnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D001665:Binding Sites; D002331:Carnitine / Q000031:analogs & derivatives*; D002332:Carnitine O-Acetyltransferase / Q000037:antagonists & inhibitors*; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D010856:Columbidae; D007700:Kinetics; D008930:Mitochondria, Liver / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D009132:Muscles / Q000201:enzymology; D010101:Oxygen Consumption; D013329:Structure-Activity Relationship
chemical_list: C049831:hemiacetylcarnitinium; D000108:Acetylcarnitine; D000217:Acyltransferases; D000123:Acetyltransferases; D002334:Carnitine O-Palmitoyltransferase; D002332:Carnitine O-Acetyltransferase; D002331:Carnitine