Reductive. beta. -scission of the hydroperoxides of fatty acids and xenobiotics: Role of alcohol-inducible cytochrome P-450
- The Univ. of Michigan, Ann Arbor (USA)
As shown previously in this laboratory, purified rabbit liver microsomal cytochrome P-450 form 2 (P-450 IIB4) catalyzes the reductive cleavage of hydroperoxides to yield hydrocarbons and either aldehydes or ketones. The authors have proposed that lipid hydroperoxides are the physiological substrates for the cleavage reaction and have shown that with 13-hydroperoxy-9,11-octadecadienoic acid the formation of pentane is roughly equimolar with respect to the NADPH consumed. In the present study, the other product was isolated and identified as 13-oxo-9,11-tridecadienoic acid. Of particular interest, the alcohol-inducible form of liver microsomal cytochrome P-450 form 3a (P-450 IIE1) is the most active of the isozymes examined in the reductive {beta}-scission of the 13-hydroperoxide derived from linoleic acid and the 15-hydroperoxide derived from arachidonic acid as well as the model compounds cumyl hydroperoxide and t-butyl hydroperoxide. The occurrence of the reductive cleavage reaction in liver microsomal membranes was demonstrated, and microsomes from animals treated with ethanol or acetone or phenobarbital were more active than those from untreated animals. They suggest that the alcohol-inducible P-450, in addition to its known deleterious effects in chemical toxicity and chemical carcinogenesis, may enhance the reductive cleavage of lipid hydroperoxides with a resultant loss in membrane integrity.
- OSTI ID:
- 6148684
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:14; ISSN 0027-8424; ISSN PNASA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
ALCOHOLS
ANIMALS
ARACHIDONIC ACID
BIOCHEMISTRY
BODY
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHEMICAL REACTIONS
CHEMISTRY
CYTOCHROMES
DECOMPOSITION
DIGESTIVE SYSTEM
ENZYMATIC HYDROLYSIS
GLANDS
HYDROLYSIS
HYDROXY COMPOUNDS
LINOLEIC ACID
LIVER
LYSIS
MAGNETIC RESONANCE
MAMMALS
MICROSOMES
MONOCARBOXYLIC ACIDS
NUCLEAR MAGNETIC RESONANCE
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
OXYGEN COMPOUNDS
PEROXIDES
PIGMENTS
PROTEINS
RABBITS
RESONANCE
RIBOSOMES
SOLVOLYSIS
STOICHIOMETRY
VERTEBRATES
XENOBIOTICS