The physiological role of monocarboxylate transport in brown adipose tissue mitochondria has been reevaluated. We studied pyruvate, alpha-ketoisovalerate, alpha-ketoisocaproate, and phenylpyruvate uniport via the uncoupling protein (UCP1) as a GDP-sensitive swelling in K+ salts induced by valinomycin or by monensin and carbonyl cyanide-p-(trifluoromethoxy)phenylhydrazone in Na+ salts. We have demonstrated that this uniport is inhibited by fatty acids. GDP inhibition in K+ salts was not abolished by an uncoupler, indicating a negligible monocarboxylic acid penetration via the lipid bilayer. In contrast, the electroneutral pyruvate uptake (swelling in ammonium pyruvate or potassium pyruvate induced by change in pH) mediated by the pyruvate carrier was inhibited by its specific inhibitor alpha-cyano-4-hydroxycinnamate but not by fatty acids. Moreover, alpha-cyano-4-hydroxycinnamate enhanced the energization of brown adipose tissue mitochondria, which was monitored fluorometrically by 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide and safranin O. Consequently, we suggest that UCP1 might participate in futile cycling of unipolar ketocarboxylates under certain physiological conditions while expelling these anions from the matrix. The cycle is completed on their return via the pyruvate carrier in an H+ symport mode.

• MeSH
• biologický transport MeSH
• guanosindifosfát farmakologie   MeSH
• hnědá tuková tkáň metabolismus   MeSH
• iontové kanály MeSH
• karbonylkyanid-p-trifluormethoxyfenylhydrazon farmakologie   MeSH
• kinetika MeSH
• koncentrace vodíkových iontů MeSH
• křečci praví MeSH
• křeček rodu Mesocricetus MeSH
• kyseliny fenylpyrohroznové farmakologie   MeSH
• kyseliny karboxylové metabolismus   MeSH
• kyseliny kumarové farmakologie   MeSH
• lipidové dvojvrstvy MeSH
• membránové proteiny metabolismus   MeSH
• mitochondriální proteiny MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• monensin farmakologie   MeSH
• pyruváty metabolismus   MeSH
• rotenon farmakologie   MeSH
• transportní proteiny metabolismus   MeSH
• uncoupling protein 1 MeSH
• valinomycin farmakologie   MeSH
• zduření mitochondrií účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alpha-cyano-4-hydroxycinnamate MeSH Prohlížeč
• guanosindifosfát MeSH
• iontové kanály MeSH
• karbonylkyanid-p-trifluormethoxyfenylhydrazon MeSH
• kyseliny fenylpyrohroznové MeSH
• kyseliny karboxylové MeSH
• kyseliny kumarové MeSH
• lipidové dvojvrstvy MeSH
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• monensin MeSH
• phenylpyruvic acid MeSH Prohlížeč
• pyruváty MeSH
• rotenon MeSH
• transportní proteiny MeSH
• uncoupling protein 1 MeSH
• valinomycin MeSH