Stereoisomeric acylamidomorpholinium carnitine analogues: selective inhibitors of carnitine palmitoyltransferase I and II.
Acylamidomorpholinium carnitine analogues, 6-(tetradecanamidomethyl- and -hexadecanamidomethyl)-4,4-dimethylmorpholin-4-ium-2-a cetate, 1, synthesized as complete sets of stereoisomers, were assayed as inhibitors for isozymes of carnitine palmitoyltransferase (CPT). Microsomal CPT isoymes showed modest discrimination among the stereoisomers; while rat-liver mitochondrial CPT-I and CPT-II showed distinct differences. The tetradecanamidomethyl analogue of (2R,6S)-1 activated CPT-I but inhibited CPT-II.
Savle
P S
PS
Department of Chemistry, Virginia Tech, Blacksburg 24061-0212, USA.
Pande
S V
SV
Lee
T S
TS
Gandour
R D
RD
D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives*; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D015394:Molecular Structure; D009025:Morpholines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism
C400930:6-(hexadecanamidomethyl)-4,4-dimethylmorpholin-4-ium-2-acetate; C400929:6-(tetradecanamidomethyl)-4,4-dimethylmorpholin-4-ium-2-acetate; D004791:Enzyme Inhibitors; D009025:Morpholines; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine