Natural and azido fatty acids inhibit phosphate transport and activate fatty acid anion uniport mediated by the mitochondrial phosphate carrier
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
11085992
DOI
10.1074/jbc.m009409200
PII: S0021-9258(18)46263-1
Knihovny.cz E-resources
- MeSH
- Affinity Labels pharmacology MeSH
- Biological Transport, Active MeSH
- Diphosphonates pharmacology MeSH
- Phosphates metabolism MeSH
- Ion Transport MeSH
- Kinetics MeSH
- Rats MeSH
- Lauric Acids pharmacology MeSH
- Palmitic Acids pharmacology MeSH
- Fatty Acids metabolism pharmacology MeSH
- Mitochondria drug effects metabolism MeSH
- Rats, Wistar MeSH
- Phosphate-Binding Proteins MeSH
- Carrier Proteins antagonists & inhibitors metabolism MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 12-(4-azido-2-nitrophenylamino)dodecanoic acid MeSH Browser
- 16-(4-azido-2-nitrophenylamino)hexadecanoic acid MeSH Browser
- Affinity Labels MeSH
- Diphosphonates MeSH
- Phosphates MeSH
- Lauric Acids MeSH
- Palmitic Acids MeSH
- Fatty Acids MeSH
- Phosphate-Binding Proteins MeSH
- Carrier Proteins MeSH
The electroneutral P(i) uptake via the phosphate carrier (PIC) in rat liver and heart mitochondria is inhibited by fatty acids (FAs), by 12-(4-azido-2-nitrophenylamino)dodecanoic acid (AzDA) and heptylbenzoic acid ( approximately 1 microm doses) and by lauric, palmitic, or 12-azidododecanoic acids ( approximately 0.1 mm doses). In turn, reconstituted E. coli-expressed yeast PIC mediated anionic FA uniport with a similar pattern leading to FA cycling and H(+) uniport. The kinetics of P(i)/P(i) exchange on recombinant PIC in the presence of AzDA better corresponded to a competitive inhibition mechanism. Methanephosphonate was identified as a new PIC substrate. Decanephosphonate, butanephosphonate, 4-nitrophenylphosphate, and other P(i) analogs were not translocated and did not inhibit P(i) transport. However, methylenediphosphonate and iminodi(methylenephosphonate) inhibited both electroneutral P(i) uptake and FA cycling via PIC. AzDA analog 16-(4-azido-2-nitrophenylamino)-[(3)H(4)]-hexadecanoic acid ((3)H-AzHA) bound upon photoactivation to several mitochondrial proteins, including the 30- and 34-kDa bands. The latter was ascribed to PIC due to its specific elution pattern on Blue Sepharose and Affi-Gel. (3)H-AzHA photolabeling of recombinant PIC was prevented by methanephosphonate and diphosphonates and after premodification with 4-azido-2-nitrophenylphosphate. Hence, the demonstrated PIC interaction with monovalent long-chain FA anions, but with divalent phosphonates of short chain only, indicates a pattern distinct from that valid for the mitochondrial uncoupling protein-1.
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