Open AccessFatty Acid Interaction with the Hydroxylating Enzyme System of Rat Liver Microsomes
Author(s) -
Orrenius S.,
Thor H.
Publication year - 1969
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1969.tb00624.x
Subject(s) - microsome , chemistry , mixed function oxidase , cytochrome , oxidase test , microsoma , oxidative phosphorylation , fatty acid , enzyme , biochemistry , demethylation , organic chemistry , gene expression , dna methylation , gene
Addition of a low concentration of laurate ( K m = 6 μM) to rat liver microsomes in the presence of NADPH was found to stimulate the rate of NADPH disappearance parallel to the formation of oxidized metabolites, mainly ω‐hydroxy laurate. When added to a suspension of liver microsomes laurate gave rise to the formation of a “type I” spectral change indicating an interaction of the fatty acid with the microsomal mixed function oxidase. Whereas laurate present in an optimal concentration for ω‐oxidation caused a competitive inhibition of the oxidative demethylation of drugs, this activity as well as the ω‐oxidation activity was almost completely extinguished in the presence of a high fatty acid concentration (approx. 3 mM). At this concentration laurate had a solubilizing effect on the microsomes which was associated with a conversion of cytochrome P‐450 to the enzymically inactive P‐420 form.