Stereoselective interaction of 2-halo-acyl-CoA derivatives with medium chain acyl-CoA dehydrogenase from pig kidney.

Abstract:

: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.

journal_name

Arch Biochem Biophys

authors

Cummings JG,Thorpe C

doi

10.1006/abbi.1993.1184

subject

Has Abstract

pub_date

1993-04-01 00:00:00

pages

85-91

issue

1

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(83)71184-7

journal_volume

302

pub_type

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