tion pathway are located. The acyl-CoAs, particularly the long-chain ones, cannot easily pass the mitochondrial inner membrane; their translocation is made possible by the CPT system. The acyl moiety is transferred from CoA to carnitine by Cpt1 - an integral membrane protein of the outer mitochondrial membrane. Note that Cpt1 is subject to inhibition by malonyl-CoA, the substrate for the fatty acid biosynthetic pathway. The translocase (Slc25a20) facilitates the translocation of acylcarnitine across the mitochondrial inner membrane where Cpt2 catalyzes the transfer of the acyl group from carnitine to CoA. The acyl-CoA thioesters can now undergo beta-oxidation. The beta-oxidation pathway, generally described as a spiral, consists of a [repeating] cycle of four reactions that produces acetyl-CoA and an acyl-CoA that is two carbon shorter. The spiral repeats itself until the entire acyl-CoA has been broken down to acetyl-CoA. In the first reaction, acyl-CoA is dehydrogenated to trans-2-enoyl-CoA by members of the FAD-containing acyl-CoA dehydrogenase family (Acad). The family contains several members named after their chain-length specificity; of these, the long-chain acyl-CoA dehydrogenase may participate in the beta-oxidation of unsaturated fatty acids. The FADH2 produced in the reaction is re-oxidized by transferring electrons from the dehydrogenase to the FAD group of Etf and from there to Etfdh which feeds the electrons into the electron transport chain thus linking the dehydrogenases to the oxidative phosphorylation pathway culminating in ATP synthesis. In the second reaction, 2-trans-enoyl-CoA is reversibly hydrated to 3-hydroxyacyl-CoA by Echs1. 3-hydroxyacyl-CoA undergoes NAD-dependent dehydrogenation to produce 3-ketoacyl-CoA, a reaction catalyzed by Hadh. The last step involves a thiolase-mediated (Acaa2) cleavage of the thioester bond to release acetyl-CoA and an acyl-CoA which is two carbons shorter and enters another round of the spiral. The last three steps of the beta-oxidation of long-chain acyl-CoA esters - the hydratase, dehydrogenase and thiolase reactions - are carried out by a trifunctional enzyme. The protein consists of two subunits: the alpha subunit (Hadha) catalyzes the first two reactions, the beta subunit (Hadhb) catalyzes the third. While the mono-enzymes are soluble matrix proteins, the trifunctional enzyme is associated with the inner mitochondrial membrane. Disorders of beta-oxidation pathway have been associated with several conditions. To see the ontology report for GViewer, annotations and download, click here
[Click to see the ontology report for associated GO term - GO:0006635, related Kegg map - map00071]...(less)