Linked Life Data

1156402

Source:http://linkedlifedata.com/resource/pubmed/id/1156402

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1975-11-6
pubmed:abstractText
1. Studies on the kinetics of pyruvate transport into mitochondria by an 'inhibitor-stop' technique were hampered by the decarboxylation of pyruvate by mitochondria even in the presence of rotenone. Decarboxylation was minimal at 6 degrees C. At this temperature the Km for pyruvate was 0.15 mM and Vmax. was 0.54nmol/min per mg of protein; alpha-cyano-4-hydroxycinnamate was found to be a non-competitive inhibitor, Ki 6.3 muM, and phenyl-pyruvate a competitive inhibitor, Ki 1.8 mM. 2. At 100 muM concentration, alpha-cyano-4-hydroxycinnamate rapidly and almost totally inhibited O2 uptake by rat heart mitochondria oxidizing pyruvate. Inhibition could be detected at concentrations of inhibitor as low as 1 muM although inhibition took time to develop at this concentration. Inhibition could be reversed by diluting out the inhibitor. 3. Various analogues of alpha-cyano-4-hydroxycinnamate were tested on rat liver and heart mitochondria. The important structural features appeared to be the alpha-cyanopropenoate group and the hydrophobic aromatic side chain. Alpha-Cyanocinnamate, alpha-cyano-5-phenyl-2,4-pentadienoate and compound UK 5099 [alpha-cyano-beta-(2-phenylindol-3-yl)acrylate] were all more powerful inhibitors than alpha-cyano-4-hydroxycinnamate showing 50% inhibition of pyruvate-dependent O2 consumption by rat heart mitochondria at concentrations of 200, 200 and 50 nM respectively. 4. The specificity of the carrier for its substrate was studied by both influx and efflux experiments. Oxamate, 2-oxobutyrate, phenylpyruvate, 2-oxo-4-methyl-pentanoate, chloroacetate, dichloroacetate, difluoroacetate, 2-chloropropionate, 3-chloropropionate and 2,2-dichloropropionate all exchanged with pyruvate, whereas acetate, lactate and trichloroacetate did not. 5. Pyruvate entry into the mitochondria was shown to be accompanied by the transport of a proton (or by exchange with an OH-ion). This proton flux was inhibited by alpha-cyano-4-hydroxycinnamate and allowed measurements of pyruvate transport at higher temperatures to be made. The activation energy of mitochondrial pyruvate transport was found to be 113 kJ (27 kcal)/mol and by extrapolation the rate of transport of pyruvate at 37 degrees C to be 42 nmol/min per mg of protein. The possibility that pyruvate transport into mitochondria may be rate limiting and involved in the regulation of gluconegenesis is discussed. 6. The transport of various monocarboxylic acids into mitochondria was studied by monitoring proton influx. The transport of dichloroacetate, difluoroacetate and oxamate appeared to be largely dependent on the pyruvate carrier and could be inhibited by pyruvate-transport inhibitors. However, many other halogenated and 2-oxo acids which could exchange with pyruvate on the carrier entered freely even in the presence of inhibitor.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-1171687, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-4304225, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-4342011, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-4413896, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-4418160, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-4462746, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-4478069, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-4658997, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-4762750, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-4768903, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-4822737, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-4827853, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-5025933, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-5076196, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-5094670, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-5348074, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-5354962, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-5440627, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-5499232, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-5581324, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-5679958, http://linkedlifedata.com/resource/pubmed/commentcorrection/1156402-5725814
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0264-6021
pubmed:author
pubmed:issnType
Print
pubmed:volume
148
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
85-96
pubmed:dateRevised
2010-9-9
pubmed:meshHeading
pubmed:year
1975
pubmed:articleTitle
The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors.
pubmed:publicationType
Journal Article, In Vitro