Linked Life Data

15208325

Source:http://linkedlifedata.com/resource/pubmed/id/15208325

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
2004-9-6
pubmed:abstractText
Elucidation of the regulation of uncoupling protein 1 (UCP1) activity in its native environment, i.e. the inner membrane of brown-fat mitochondria, has been hampered by the presence of UCP1-independent, quantitatively unresolved effects of investigated regulators on the brown-fat mitochondria themselves. Here we have utilized the availability of UCP1-ablated mice to dissect UCP1-dependent and UCP1-independent effects of regulators. Using a complex-I-linked substrate (pyruvate), we found that UCP1 can mediate a 4-fold increase in thermogenesis when stimulated with the classical positive regulator fatty acids (oleate). After demonstrating that the fatty acids act in their free form, we found that UCP1 increased fatty acid sensitivity approximately 30-fold (as compared with the 1.5-fold increase reported earlier based on nominal fatty acid values). By identifying the UCP1-mediated fraction of the response, we could conclude that the interaction between purine nucleotides (GDP) and fatty acids (oleate) unexpectedly displayed simple competitive kinetics. In GDP-inhibited mitochondria, oleate apparently acted as an activator. However, only a model in which UCP1 is inherently active (i.e."activating" fatty acids cannot be included in the model), where GDP functions as an inhibitor with a K(m) of 0.05 mm, and where oleate functions as a competitive antagonist for the GDP effect (with a K(i) of 5 nm) can fit all of the experimental data. We conclude that, when examined in its native environment, UCP1 functions as a proton (equivalent) carrier in the absence of exogenous or endogenous fatty acids.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38236-48
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15208325-Adipose Tissue, Brown, pubmed-meshheading:15208325-Animals, pubmed-meshheading:15208325-Blotting, Southern, pubmed-meshheading:15208325-Carrier Proteins, pubmed-meshheading:15208325-Dose-Response Relationship, Drug, pubmed-meshheading:15208325-Fatty Acids, pubmed-meshheading:15208325-Guanosine Diphosphate, pubmed-meshheading:15208325-Ion Channels, pubmed-meshheading:15208325-Kinetics, pubmed-meshheading:15208325-Membrane Proteins, pubmed-meshheading:15208325-Mice, pubmed-meshheading:15208325-Mice, Inbred C57BL, pubmed-meshheading:15208325-Mice, Transgenic, pubmed-meshheading:15208325-Mitochondria, pubmed-meshheading:15208325-Mitochondrial Proteins, pubmed-meshheading:15208325-Oleic Acid, pubmed-meshheading:15208325-Oxygen, pubmed-meshheading:15208325-Oxygen Consumption, pubmed-meshheading:15208325-Protein Binding, pubmed-meshheading:15208325-Purines, pubmed-meshheading:15208325-Pyruvic Acid, pubmed-meshheading:15208325-Sensitivity and Specificity, pubmed-meshheading:15208325-Time Factors
pubmed:year
2004
pubmed:articleTitle
Native UCP1 displays simple competitive kinetics between the regulators purine nucleotides and fatty acids.
pubmed:affiliation
Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't