(2E)-Glutaconylcarnitine is an acylcarnitine. The general role of acylcarnitines is to transport acyl-groups, organic acids and fatty acids, from the cytoplasm into the mitochondria so that they can be broken down to produce energy. First,(2E)-glutaconic acid is transported into the cell via the long-chain fatty acid transport protein 1 (FATP1), where it undergoes a reaction to form(2E)-glutaconyl-CoA, facilitated by the Long-chain fatty-acid CoA ligase 1 protein, which adds a CoA to the compound. (2E)-glutaconyl-CoA then enters a reaction with L-carnitine, which is transported into the cell by the organic cation/carnitine transporter 2, to form (2E)-glutaconylcarnitine, catalyzed by carnitine O-palmitoyltransferase. This enzyme resides in the mitochondrial outer membrane, and as the reaction takes place, the (2E)-glutaconylcarnitine is moved into the mitochondrial intermembrane space. Following the reaction, (2E)-glutaconylcarnitine is transported into the mitochondrial matrix by a mitochondrial carnitine/acylcarnitine carrier protein found in the mitochondrial inner membrane. Once in the matrix, (2E)-glutaconylcarnitine and CoA are catalyzed by the carnitine O-palmitoyltransferase 2 enzyme found in the mitochondrial inner membrane to once again form (2E)-glutaconyl-CoA and L-carnitine. (2E)-Glutaconyl-CoA then enters into mitochondrial beta-oxidation to form aceytl-CoA. Acetyl-CoA can go on to enter the TCA cycle, or it can react with L-carnitine to form L-acetylcarnitine and CoA in a reaction catalyzed by Carnitine O-acetyltransferase. This reaction can occur in both directions, and L-acetylcarnitine and CoA can react to form acetyl-CoA and L-carnitine in certain circumstances. Finally, acetyl-CoA in the cytosol can be catalyzed by acetyl-CoA carboxylase 1 to form malonyl-CoA, which inhibits the action of carnitine O-palmitoyltransferase 1, preventing (2E)-glutaconyl-CoA from forming (2E)-glutaconylcarnitine and preventing it from being transported into the mitochondria. Malonyl-CoA can also react to form acetyl-CoA, in a reaction that removes a carbon dioxide molecule catalyzed by malonyl-CoA decarboxylase.

Acylcarnitine (2E)-Glutaconylcarnitine References