Stereoselective interaction of 2-halo-acyl-CoA derivatives with medium chain acyl-CoA dehydrogenase from pig kidney.
Several 2-halo-acyl-CoA derivatives have been synthesized to examine the interaction of these potential inhibitors of mitochondrial beta-oxidation with the purified medium chain acyl-CoA dehydrogenase from pig kidney. Racemic 2-bromo-, 2-chloro-, and 2-fluoro-octanoyl-CoA thioesters show 6.6, 33, and 3.5% of the activity of octanoyl-CoA in the standard assay system, respectively. Only the S-enantiomer of these 2-substituted analogues is a significant substrate of the dehydrogenase, with S-2-bromo-octanoyl-CoA showing a rate of 18% that of octanoyl-CoA, compared to about 1% for the R-isomer. The observations presented here suggest that a detailed understanding of the mode of action of 2-halo-fatty acids as inhibitors of mammalian beta-oxidation will require consideration of the metabolic fate and inhibitory effects of both enantiomers.
Cummings
J G
JG
Department of Chemistry and Biochemistry, University of Delaware, Newark 19716.
Thorpe
C
C
D000214:Acyl Coenzyme A / Q000737:chemistry / Q000378:metabolism*; D042964:Acyl-CoA Dehydrogenase; D044944:Acyl-CoA Dehydrogenases / Q000378:metabolism*; D000818:Animals; D006219:Halogens / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology*; D013053:Spectrophotometry; D013237:Stereoisomerism; D013379:Substrate Specificity; D013552:Swine
D000214:Acyl Coenzyme A; D006219:Halogens; C034681:octanoyl-coenzyme A; C080670:2-chlorooctanoyl-coenzyme A; C080671:2-fluorooctanoyl-coenzyme A; C060151:2-bromooctanoyl-coenzyme A; D044944:Acyl-CoA Dehydrogenases; D042964:Acyl-CoA Dehydrogenase