Peroxisomal beta-oxidation of 2-methyl-branched acyl-CoA esters: stereospecific recognition of the 2S-methyl compounds by trihydroxycoprostanoyl-CoA oxidase and pristanoyl-CoA oxidase.
Trihydroxycoprostanoyl-CoA oxidase and pristanoyl-CoA oxidase, purified from rat liver, both catalyse the desaturation of 2-methyl-branched acyl-CoAs. Upon incubation with the pure isomers of 2-methylpentadecanoyl-CoA, both enzymes acted only on the S-isomer. The R-isomer inhibited trihydroxycoprostanoyl-CoA oxidase but did not affect pristanoyl-CoA oxidase. The activity of both enzymes was suppressed by 3-methylheptadecanoyl-CoA. Valproyl-CoA and 2-ethylhexanoyl-CoA, however, did not influence the oxidases. Although only one isomer of 25R,S-trihydroxycoprostanovl-CoA was desaturated by trihydroxycoprostanoyl-CoA oxidase, isolated peroxisomes were able to act on both isomers, suggesting the presence of a racemase in these organelles. Given the opposite stereoselectivity of the 26-cholesterol hydroxylase and of the oxidase, the racemase is essential for bile acid formation.
Van Veldhoven
P P
PP
Katholieke Universiteit Leuven, Campus Gasthuisberg, Departement Moleculaire Celbiologie, Afdeling Farmakologie, Belgium.
Croes
K
K
Asselberghs
S
S
Herdewijn
P
P
Mannaerts
G P
GP
D000214:Acyl Coenzyme A / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D003652:Decanoic Acids / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004952:Esters; D008099:Liver / Q000201:enzymology; D008830:Microbodies / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D019998:Racemases and Epimerases; D051381:Rats; D013237:Stereoisomerism
D000214:Acyl Coenzyme A; D003652:Decanoic Acids; D004791:Enzyme Inhibitors; D004952:Esters; D010088:Oxidoreductases; C066272:pristanoyl-CoA oxidase; C063427:trihydroxycoprostanoyl-CoA oxidase; D019998:Racemases and Epimerases