Activating omega-6 polyunsaturated fatty acids and inhibitory purine nucleotides are high affinity ligands for novel mitochondrial uncoupling proteins UCP2 and UCP3
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
12670931
DOI
10.1074/jbc.m212850200
PII: S0021-9258(20)73376-4
Knihovny.cz E-zdroje
- MeSH
- adenosintrifosfát metabolismus farmakologie MeSH
- biologický transport účinky léků fyziologie MeSH
- guanosintrifosfát metabolismus farmakologie MeSH
- iontové kanály MeSH
- kinetika MeSH
- koenzymy MeSH
- kvasinky MeSH
- kyseliny laurové farmakologie MeSH
- kyseliny mastné omega-6 MeSH
- lidé MeSH
- ligandy MeSH
- liposomy metabolismus MeSH
- membránové transportní proteiny * MeSH
- mitochondriální proteiny * MeSH
- mitochondrie metabolismus MeSH
- nenasycené mastné kyseliny metabolismus farmakologie MeSH
- proteiny metabolismus MeSH
- protony MeSH
- transportní proteiny metabolismus MeSH
- tritium MeSH
- ubichinon analogy a deriváty farmakologie MeSH
- uncoupling protein 2 MeSH
- uncoupling protein 3 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenosintrifosfát MeSH
- coenzyme Q10 MeSH Prohlížeč
- guanosintrifosfát MeSH
- iontové kanály MeSH
- koenzymy MeSH
- kyseliny laurové MeSH
- kyseliny mastné omega-6 MeSH
- lauric acid MeSH Prohlížeč
- ligandy MeSH
- liposomy MeSH
- membránové transportní proteiny * MeSH
- mitochondriální proteiny * MeSH
- nenasycené mastné kyseliny MeSH
- proteiny MeSH
- protony MeSH
- transportní proteiny MeSH
- tritium MeSH
- ubichinon MeSH
- UCP2 protein, human MeSH Prohlížeč
- UCP3 protein, human MeSH Prohlížeč
- 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.
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