Uncoupling proteins: the issues from a biochemist point of view.
The functional characteristics of uncoupling proteins (UCP) are reviewed, with the main focus on the results with isolated and reconstituted proteins. UCP1 from brown adipose tissue, the paradigm of the UCP subfamily, is treated in more detail. The issues addressed are the role and mechanism of fatty acids, the nucleotide binding, the regulation by pH and the identification by mutagenesis of residues involved in these functions. The transport and regulatory functions of UCP2 and 3 are reviewed in comparison to UCP1. The inconsistencies of a proposed nucleotide insensitive H(+) transport by these UCPs as concluded from the expression in yeast and Escherichia coli are elucidated. In both expression system UCP 2 and 3 are not in or cannot be converted to a functionally native state and thus also for these UCPs a nucleotide regulated H (+) transport is postulated.
Institut für Physiologische Chemie der Universität München, Schillerstrasse 44, D-80336 Munich, Germany. klingenberg@pbm.med.uni-muenchen.de
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D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D024101:Mitochondrial Proteins; D008956:Models, Chemical; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009711:Nucleotides / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011510:Proteolipids / Q000378:metabolism; D017494:Proton Pumps / Q000378:metabolism; D014475:Uncoupling Agents / Q000378:metabolism; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009711:Nucleotides; D011506:Proteins; D011510:Proteolipids; D017494:Proton Pumps; C000604371:UCP1 protein, human; C000604389:UCP2 protein, human; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; C020485:proteoliposomes; D000226:Mitochondrial ADP, ATP Translocases