Document Detail


Effect of phenobarbital treatment and cytochrome P-450 inhibitors on the laurate omega- and (omega - 1)-hydroxylase activities of rat liver microsomes.
MedLine Citation:
PMID:  6104577     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The omega- and (omega - 1)-hydroxylase activities for lauric acid were investigated in rat liver microsomes. Treatment of rats with phenobarbital selectively induced the hydroxylation of the fatty acid (omega - 1)-hydroxylase activity two- to threefold, but had little effect on the omega-hydroxylation reaction. SKF 525-A, metyrapone, and alpha-naphthoflavone inhibited (omega - 1)-hydroxylation, but had only neglible effects on omega-hydroxylation. Metyrapone at 10(-4) inhibited the specific activity of (omega - 1)-hydroxylase 70% in phenobarbital-pretreated rats, but produced only a 10% inhibition of the omega-hydroxylation activity. alpha-Naphthoflavone at 10(-4)M inhibited (omega - 1)-hydroxylase activity 60% in untreated and beta-haphthoflavone-pretreated rats, while omega-hydroxylase activity was decreased only 20%. A selective effect was also observed when microsomes were stored overnight at 4 degrees C. Declines of 50% and 70% were observed in the (omega - 1)-hydroxylase activities after 24 and 48 hr, respectively, whereas omega-hydroxylation decreased only 10-20%. The differential effects on omega- and (omega - 1)-hydroxylase activities of a variety of conditions suggest that distinct cytochromes P-450 mediate the two fattty acid hydroxylases in liver microsomes.
Authors:
R T Okita; B S Masters
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  8     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:    1980 May-Jun
Date Detail:
Created Date:  1980-09-26     Completed Date:  1980-09-26     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  147-51     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Alkane 1-Monooxygenase
Animals
Benzoflavones*
Cold Temperature
Cytochrome P-450 Enzyme System / antagonists & inhibitors*
Flavonoids / pharmacology
Laurates / metabolism*
Lauric Acids / antagonists & inhibitors,  metabolism*
Male
Metyrapone / pharmacology
Microsomes, Liver / drug effects,  enzymology*
Mixed Function Oxygenases / antagonists & inhibitors,  metabolism*
Phenobarbital / pharmacology*
Proadifen / pharmacology
Rats
beta-Naphthoflavone
Chemical
Reg. No./Substance:
0/Benzoflavones; 0/Flavonoids; 0/Laurates; 0/Lauric Acids; 302-33-0/Proadifen; 50-06-6/Phenobarbital; 54-36-4/Metyrapone; 604-59-1/alpha-naphthoflavone; 6051-87-2/beta-Naphthoflavone; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Mixed Function Oxygenases; EC 1.14.15.3/Alkane 1-Monooxygenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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