Document Detail

Disturbance of mitochondrial energy homeostasis caused by the metabolites accumulating in LCHAD and MTP deficiencies in rat brain.
MedLine Citation:
PMID:  20399795     Owner:  NLM     Status:  MEDLINE    
AIMS: We investigated the in vitro effects of 3-hydroxydodecanoic (3HDA), 3-hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids, which accumulate in tissues of patients affected by mitochondrial trifunctional protein (MTP) and isolated long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies, on various parameters of energy homeostasis in mitochondrial preparations from brain of young rats.
MAIN METHODS: We measured the respiratory parameters state 4, state 3, respiratory control ratio (RCR) and ADP/O ratio by the rate of oxygen consumption, as well as the mitochondrial membrane potential and the matrix NAD(P)H levels in the presence of the fatty acids.
KEY FINDINGS: We found that 3HDA, 3HTA and 3HPA markedly increased state 4 respiration and diminished the RCR using glutamate plus malate or succinate as substrates. 3HTA and 3HPA also diminished the mitochondrial membrane potential and the matrix NAD(P)H levels. In addition, 3HTA decreased state 3 respiration using glutamate/malate, but not pyruvate/malate or succinate as substrates. Our data indicate that the long-chain 3-hydroxy fatty acids that accumulate in LCHAD/MTP deficiencies act as uncouplers of oxidative phosphorylation, while 3HTA also behaves as a metabolic inhibitor.
SIGNIFICANCE: It is presumed that impairment of brain energy homeostasis caused by these endogenous accumulating compounds may contribute at least in part to the neuropathology of LCHAD/MTP deficiencies.
Anelise M Tonin; Gustavo C Ferreira; Mateus Grings; Carolina M Viegas; Estela N Busanello; Alexandre U Amaral; Angela Zanatta; Patrícia Fernanda Schuck; Moacir Wajner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-20
Journal Detail:
Title:  Life sciences     Volume:  86     ISSN:  1879-0631     ISO Abbreviation:  Life Sci.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-11     Completed Date:  2010-05-27     Revised Date:  2012-11-16    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  825-31     Citation Subset:  IM    
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
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MeSH Terms
3-Hydroxyacyl CoA Dehydrogenases / deficiency*,  drug effects,  metabolism
Brain / drug effects*,  metabolism
Energy Metabolism / drug effects*
Homeostasis / drug effects
Lauric Acids / pharmacology*
Membrane Potential, Mitochondrial / drug effects
Mitochondria / drug effects*,  metabolism
Multienzyme Complexes / deficiency*,  drug effects,  metabolism
Myristic Acids / pharmacology*
NADP / metabolism
Oxygen Consumption / drug effects
Rats, Wistar
Reg. No./Substance:
0/Lauric Acids; 0/Multienzyme Complexes; 0/Myristic Acids; 0/mitochondrial fatty acid beta-oxidation trifunctional protein; 1883-13-2/3-hydroxydodecanoic acid; 1961-72-4/beta-hydroxymyristic acid; 53-59-8/NADP; EC 3-hydroxyacyl CoA dehydrogenase; EC CoA Dehydrogenases

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

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