Document Detail


Lipoic acid reduces the activities of biotin-dependent carboxylases in rat liver.
MedLine Citation:
PMID:  9278559     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the past, lipoic acid has been administered to patients and test animals as therapy for diabetic neuropathy and various intoxications. Lipoic acid and the vitamin biotin have structural similarities. We sought to determine whether the chronic administration of lipoic acid affects the activities of biotin-dependent carboxylases. For 28 d, rats received daily intraperitoneal injections of one of the following: 1) a small dose of lipoic acid [4.3 micromol/( kg.d)]; 2) a large dose of lipoic acid [15.6 micromol/(kg.d)]; or 3) a large dose of lipoic acid plus biotin [15.6 and 2.0 micromol/(kg.d), respectively]. Another group received n-hexanoic acid [14.5 micromol/(kg.d)], which has structural similarities to lipoic acid and biotin and thus served as a control for the specificity of lipoic acid. A fifth group received phosphatidylcholine in saline injections and served as the vehicle control. The rat livers were assayed for the activities of acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and beta-methylcrotonyl-CoA carboxylase. Urine was analyzed for lipoic acid; serum was analyzed for indicators of liver damage and metabolic aberrations. The mean activities of pyruvate carboxylase and beta-methylcrotonyl-CoA carboxylase were 28-36% lower in the lipoic acid-treated rats compared with vehicle controls (P < 0.05). Rats treated with lipoic acid plus biotin had normal carboxylase activities. Carboxylase activities in livers of n-hexanoic acid-treated rats were normal despite some evidence of liver injury. Propionyl-CoA carboxylase and acetyl-CoA carboxylase were not significantly affected by administration of lipoic acid. This study provides evidence consistent with the hypothesis that chronic administration of lipoic acid lowers the activities of pyruvate carboxylase and beta-methylcrotonyl-CoA carboxylase in vivo by competing with biotin.
Authors:
J Zempleni; T A Trusty; D M Mock
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of nutrition     Volume:  127     ISSN:  0022-3166     ISO Abbreviation:  J. Nutr.     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1997-10-22     Completed Date:  1997-10-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0404243     Medline TA:  J Nutr     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1776-81     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, University of Arkansas for Medical Sciences and the Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetyl-CoA Carboxylase / drug effects*,  metabolism
Animals
Biotin / administration & dosage,  pharmacology*
Dose-Response Relationship, Drug
Injections, Intraperitoneal
Liver / enzymology*
Male
Pyruvate Carboxylase / drug effects*,  metabolism
Rats
Rats, Sprague-Dawley
Thioctic Acid / administration & dosage,  pharmacology*,  urine
Grant Support
ID/Acronym/Agency:
36823//PHS HHS
Chemical
Reg. No./Substance:
58-85-5/Biotin; 62-46-4/Thioctic Acid; EC 6.4.1.1/Pyruvate Carboxylase; EC 6.4.1.2/Acetyl-CoA Carboxylase

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


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