Structural insight into function and regulation of carnitine palmitoyltransferase
The control of fatty acid translocation across the mitochondrial membrane is mediated by the carnitine palmitoyltransferase (CPT) system. Modulation of its functionality has simultaneous effects on fatty acid and glucose metabolism. This encourages use of the CPT system as drug target for reduction...
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| Veröffentlicht in: | Cellular and molecular life sciences : CMLS 2009-08, Vol.66 (15), p.2489-2501 |
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| creator | Rufer, Arne C Thoma, Ralf Hennig, Michael |
| description | The control of fatty acid translocation across the mitochondrial membrane is mediated by the carnitine palmitoyltransferase (CPT) system. Modulation of its functionality has simultaneous effects on fatty acid and glucose metabolism. This encourages use of the CPT system as drug target for reduction of gluconeogenesis and restoration of lipid homeostasis, which are beneficial in the treatment of type 2 diabetes mellitus and obesity. Recently, crystal structures of CPT-2 were determined in uninhibited forms and in complexes with inhibitory substrate-analogs with anti-diabetic properties in animal models and in clinical studies. The CPT-2 crystal structures have advanced understanding of CPT structure-function relationships and will facilitate discovery of novel inhibitors by structure-based drug design. However, a number of unresolved questions regarding the biochemistry and pharmacology of CPT enzymes remain and are addressed in this review. |
| doi_str_mv | 10.1007/s00018-009-0035-1 |
| format | Article |
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Modulation of its functionality has simultaneous effects on fatty acid and glucose metabolism. This encourages use of the CPT system as drug target for reduction of gluconeogenesis and restoration of lipid homeostasis, which are beneficial in the treatment of type 2 diabetes mellitus and obesity. Recently, crystal structures of CPT-2 were determined in uninhibited forms and in complexes with inhibitory substrate-analogs with anti-diabetic properties in animal models and in clinical studies. The CPT-2 crystal structures have advanced understanding of CPT structure-function relationships and will facilitate discovery of novel inhibitors by structure-based drug design. However, a number of unresolved questions regarding the biochemistry and pharmacology of CPT enzymes remain and are addressed in this review.</description><identifier>ISSN: 1420-682X</identifier><identifier>EISSN: 1420-9071</identifier><identifier>DOI: 10.1007/s00018-009-0035-1</identifier><identifier>PMID: 19430727</identifier><language>eng</language><publisher>Basel: Basel : SP Birkhäuser Verlag Basel</publisher><subject>Animal models ; Animals ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Carnitine O-Palmitoyltransferase - chemistry ; Carnitine O-Palmitoyltransferase - genetics ; Carnitine O-Palmitoyltransferase - metabolism ; carnitine palmitoyltransferase ; Cell Biology ; Diabetes ; Diabetes Mellitus, Type 2 - metabolism ; Drug discovery ; Enzyme isoforms ; Enzymes ; Fatty acids ; Fatty Acids - metabolism ; Humans ; Isoenzymes - chemistry ; Isoenzymes - genetics ; Isoenzymes - metabolism ; Life Sciences ; Lipids ; Malonyl-CoA ; Metabolism ; Mitochondria - metabolism ; Mitochondria - ultrastructure ; Mitochondrial Membranes - metabolism ; Models, Molecular ; Molecular Structure ; Molecular Weight ; Pharmacology ; Protein Conformation ; Protein Processing, Post-Translational ; Review ; Studies ; Tissue Distribution ; Translocation ; Type 2 diabetes mellitus</subject><ispartof>Cellular and molecular life sciences : CMLS, 2009-08, Vol.66 (15), p.2489-2501</ispartof><rights>Birkhäuser Verlag, Basel/Switzerland 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-86b7f8f96f75c79debdc13030fec1661c4cefe8708a07d20f06617597b0564fa3</citedby><cites>FETCH-LOGICAL-c449t-86b7f8f96f75c79debdc13030fec1661c4cefe8708a07d20f06617597b0564fa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11115844/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11115844/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19430727$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rufer, Arne C</creatorcontrib><creatorcontrib>Thoma, Ralf</creatorcontrib><creatorcontrib>Hennig, Michael</creatorcontrib><title>Structural insight into function and regulation of carnitine palmitoyltransferase</title><title>Cellular and molecular life sciences : CMLS</title><addtitle>Cell. Mol. Life Sci</addtitle><addtitle>Cell Mol Life Sci</addtitle><description>The control of fatty acid translocation across the mitochondrial membrane is mediated by the carnitine palmitoyltransferase (CPT) system. Modulation of its functionality has simultaneous effects on fatty acid and glucose metabolism. This encourages use of the CPT system as drug target for reduction of gluconeogenesis and restoration of lipid homeostasis, which are beneficial in the treatment of type 2 diabetes mellitus and obesity. Recently, crystal structures of CPT-2 were determined in uninhibited forms and in complexes with inhibitory substrate-analogs with anti-diabetic properties in animal models and in clinical studies. The CPT-2 crystal structures have advanced understanding of CPT structure-function relationships and will facilitate discovery of novel inhibitors by structure-based drug design. However, a number of unresolved questions regarding the biochemistry and pharmacology of CPT enzymes remain and are addressed in this review.</description><subject>Animal models</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Carnitine O-Palmitoyltransferase - chemistry</subject><subject>Carnitine O-Palmitoyltransferase - genetics</subject><subject>Carnitine O-Palmitoyltransferase - metabolism</subject><subject>carnitine palmitoyltransferase</subject><subject>Cell Biology</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Drug discovery</subject><subject>Enzyme isoforms</subject><subject>Enzymes</subject><subject>Fatty acids</subject><subject>Fatty Acids - metabolism</subject><subject>Humans</subject><subject>Isoenzymes - chemistry</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - metabolism</subject><subject>Life Sciences</subject><subject>Lipids</subject><subject>Malonyl-CoA</subject><subject>Metabolism</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - ultrastructure</subject><subject>Mitochondrial Membranes - metabolism</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>Molecular Weight</subject><subject>Pharmacology</subject><subject>Protein Conformation</subject><subject>Protein Processing, Post-Translational</subject><subject>Review</subject><subject>Studies</subject><subject>Tissue Distribution</subject><subject>Translocation</subject><subject>Type 2 diabetes 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The CPT-2 crystal structures have advanced understanding of CPT structure-function relationships and will facilitate discovery of novel inhibitors by structure-based drug design. However, a number of unresolved questions regarding the biochemistry and pharmacology of CPT enzymes remain and are addressed in this review.</abstract><cop>Basel</cop><pub>Basel : SP Birkhäuser Verlag Basel</pub><pmid>19430727</pmid><doi>10.1007/s00018-009-0035-1</doi><tpages>13</tpages></addata></record> |
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| subjects | Animal models Animals Biochemistry Biomedical and Life Sciences Biomedicine Carnitine O-Palmitoyltransferase - chemistry Carnitine O-Palmitoyltransferase - genetics Carnitine O-Palmitoyltransferase - metabolism carnitine palmitoyltransferase Cell Biology Diabetes Diabetes Mellitus, Type 2 - metabolism Drug discovery Enzyme isoforms Enzymes Fatty acids Fatty Acids - metabolism Humans Isoenzymes - chemistry Isoenzymes - genetics Isoenzymes - metabolism Life Sciences Lipids Malonyl-CoA Metabolism Mitochondria - metabolism Mitochondria - ultrastructure Mitochondrial Membranes - metabolism Models, Molecular Molecular Structure Molecular Weight Pharmacology Protein Conformation Protein Processing, Post-Translational Review Studies Tissue Distribution Translocation Type 2 diabetes mellitus |
| title | Structural insight into function and regulation of carnitine palmitoyltransferase |
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