Activating omega-6 polyunsaturated fatty acids and inhibitory purine nucleotides are high affinity ligands for novel mitochondrial uncoupling proteins UCP2 and UCP3
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
12670931
DOI
10.1074/jbc.m212850200
PII: S0021-9258(20)73376-4
Knihovny.cz E-resources
- MeSH
- Adenosine Triphosphate metabolism pharmacology MeSH
- Biological Transport drug effects physiology MeSH
- Guanosine Triphosphate metabolism pharmacology MeSH
- Ion Channels MeSH
- Kinetics MeSH
- Coenzymes MeSH
- Yeasts MeSH
- Lauric Acids pharmacology MeSH
- Fatty Acids, Omega-6 MeSH
- Humans MeSH
- Ligands MeSH
- Liposomes metabolism MeSH
- Membrane Transport Proteins * MeSH
- Mitochondrial Proteins * MeSH
- Mitochondria metabolism MeSH
- Fatty Acids, Unsaturated metabolism pharmacology MeSH
- Proteins metabolism MeSH
- Protons MeSH
- Carrier Proteins metabolism MeSH
- Tritium MeSH
- Ubiquinone analogs & derivatives pharmacology MeSH
- Uncoupling Protein 2 MeSH
- Uncoupling Protein 3 MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adenosine Triphosphate MeSH
- coenzyme Q10 MeSH Browser
- Guanosine Triphosphate MeSH
- Ion Channels MeSH
- Coenzymes MeSH
- Lauric Acids MeSH
- Fatty Acids, Omega-6 MeSH
- lauric acid MeSH Browser
- Ligands MeSH
- Liposomes MeSH
- Membrane Transport Proteins * MeSH
- Mitochondrial Proteins * MeSH
- Fatty Acids, Unsaturated MeSH
- Proteins MeSH
- Protons MeSH
- Carrier Proteins MeSH
- Tritium MeSH
- Ubiquinone MeSH
- UCP2 protein, human MeSH Browser
- UCP3 protein, human MeSH Browser
- Uncoupling Protein 2 MeSH
- Uncoupling Protein 3 MeSH
UCP2 (the lowest Km values: 20 and 29 microm, respectively) for omega-6 polyunsaturated FAs (PUFAs), all-cis-8,11,14-eicosatrienoic and all-cis-6,9,12-octadecatrienoic acids, which are also the most potent agonists of the nuclear PPARbeta receptor in the activation of UCP2 transcription. omega-3 PUFA, cis-5,8,11,14,17-eicosapentaenoic acid had lower affinity (Km, 50 microm), although as an omega-6 PUFA, arachidonic acid exhibited the same low affinity as lauric acid (Km, approximately 200 microm). These findings suggest a possible dual role of some PUFAs in activating both UCPn expression and uncoupling activity. UCP2 (UCP3)-dependent H+ translocation activated by all tested FAs was inhibited by purine nucleotides with apparent affinity to UCP2 (reciprocal Ki) decreasing in order: ADP > ATP approximately GTP > GDP >> AMP. Also [3H]GTP ([3H]ATP) binding to isolated Escherichia coli (Kd, approximately 5 microm) or yeast-expressed UCP2 (Kd, approximately 1.5 microm) or UCP3 exhibited high affinity, similar to UCP1. The estimated number of [3H]GTP high affinity (Kd, <0.4 microm) binding sites was (in pmol/mg of protein) 182 in lung mitochondria, 74 in kidney, 28 in skeletal muscle, and approximately 20 in liver mitochondria. We conclude that purine nucleotides must be the physiological inhibitors of UCPn-mediated uncoupling in vivo.
References provided by Crossref.org
FA Sliding as the Mechanism for the ANT1-Mediated Fatty Acid Anion Transport in Lipid Bilayers
Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox Signaling
Redox homeostasis in pancreatic β cells
Channel character of uncoupling protein-mediated transport
