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Arne C. Rufer Ralf Thoma Michael Hennig 《Cellular and molecular life sciences : CMLS》2009,66(15):2489-2501
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. 相似文献
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