Document Detail


Inhibition of lipid synthesis by beta beta'-tetramethyl-substituted, C14-C22, alpha, omega-dicarboxylic acids in cultured rat hepatocytes.
MedLine Citation:
PMID:  4008497     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
beta beta'-Methyl-substituted, C14-C18, alpha, omega-dicarboxylic acids (MEDICA 14-18) were found to inhibit fatty acids and cholesterol synthesis in cultured rat hepatocytes. Maximum inhibition was observed with MEDICA 16, amounting to a 50% decrease in 3H2O and acetate incorporation into fatty acids and cholesterol in the presence of 0.08 mM of the drug added to the culture medium. Inhibition of lipogenesis was not accompanied by inhibition of palmitate or glycerol esterification into neutral lipids and phospholipids. The respective capacities of MEDICA homologues of varying acyl chain length as inhibitors of fatty acid and cholesterol synthesis in cultured rat hepatocytes and in vivo (Bar-Tana, J., Rose-Kahn, G., and Srebnik, M. (1985) J. Biol. Chem. 260, 8404-8410) correlated well with their respective inhibitory effect on liver ATP-citrate lyase. Thus, MEDICA 16 inhibited liver ATP-citrate lyase competitively to citrate with a Ki of 16 microM as compared to a Km of 0.8 mM for the citrate substrate.
Authors:
G Rose-Kahn; J Bar-Tana
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  260     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1985 Jul 
Date Detail:
Created Date:  1985-08-16     Completed Date:  1985-08-16     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  8411-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetyl Coenzyme A / metabolism
Animals
Biological Transport
Cells, Cultured
Cholesterol / biosynthesis
Citrates / metabolism
Citric Acid
Dicarboxylic Acids / pharmacology*
Dose-Response Relationship, Drug
Glucose / metabolism
Lipids / biosynthesis*
Liver / drug effects,  metabolism*
Malonyl Coenzyme A / metabolism
Methylation
Mitochondria, Liver / metabolism
Palmitic Acid
Palmitic Acids / metabolism
Rats
Time Factors
Chemical
Reg. No./Substance:
0/Citrates; 0/Dicarboxylic Acids; 0/Lipids; 0/Palmitic Acids; 50-99-7/Glucose; 524-14-1/Malonyl Coenzyme A; 57-10-3/Palmitic Acid; 57-88-5/Cholesterol; 72-89-9/Acetyl Coenzyme A; 77-92-9/Citric Acid

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


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