Carnitine palmitoyl transferase reaction

Fatty acids are activated on the outer mitochondrial membrane, whereas they are oxidized in the mitochondrial matrix. A special transport mechanism is needed to carry long-chain acyl CoA molecules across the inner mitochondrial membrane. Activated long-chain fatty acids are transported across the membrane by conjugating them to carnitine, a zwitterionic alcohol. The acyl group is transferred from the sulfur atom of CoA to the hydroxyl group of carnitine to form acyl carnitine. This reaction is catalyzed by carnitine acyltransferase I (also called carnitine palmitoyl transferase I), which is bound to the outer mitochondrial membrane. 

A on the matrix side of the membrane. This reaction, which is catalyzed by carnitine acy[transferase II (carnitine palmitoyl transferase II), is simply the reverse of the reaction that takes place in the cytoplasm. The reaction is thermodynamically feasible because of the zwitterionic nature of carnitine The O-acyl link in carnitine has a high group-transfer potential, apparently because, being zwitterions, carnitine and its esters are solvated differently from most other alcohols and their esters. Finally, the translocase returns carnitine to the cytoplasmic side in exchange for an incoming acyl carnitine. 

Carnitine palmitoyltransferase I (CPTI also called carnitine acyltransferase I, CATI), the enzyme that transfers long-chain fatty acyl groups from CoA to carnitine, is located on the outer mitochondrial membrane (Fig. 23.5). Fatty acylcamitine crosses the inner mitochondrial membrane with the aid of a translocase. The fatty acyl group is transferred back to CoA by a second enzyme, carnitine palmitoyl-transferase II (CPTII or CATII). The carnitine released in this reaction returns to the cytosolic side of the mitochondrial membrane by the same translocase that brings fatty acylcamitine to the matrix side. Long-chain fatty acyl CoA, now located within the mitochondrial matrix, is a substrate for (3-oxidation. 

As shown in Figure 5.28, the first reaction in the synthesis of fatty acids is carboxylation of acetyl CoA to malonyl CoA. This is a biotin-dependent reaction (section 11.12.2) and, as discussed above (section 5.5.1), the activity of acetyl CoA carboxylase is regulated in response to insulin and glucagon. Malonyl CoA is not only the substrate for fatty acid synthesis, but also a potent inhibitor of carnitine palmitoyl transferase, so inhibiting the uptake of fatty acids into the mitochondrion for P-oxidation. 

The second site may include two possibilities one is on the carnitine acyl transferase system and the other involves formation of palmitoyl-S-pantetheine and its non-enzymatic transport through the mitochondrial membranes followed by oxidation in -oxidation system after conversion to palmitoyl CoA. The former possibility may be supported by the difference in effectiveness of pantethine between the palmitate and octanoate oxidation reactions ( Fig.3, 4 and 6 ) and between the ketogenic reactions from these two substrates ( Fig.7 ), because octanoic acid is freely permeable through the mitochondrial membranes. The latter possibility was based on the findings on the formation of acyl pantetheine in rat liver micro-somes [ 10 ] and on the enzymatic interconversion between acyl CoA and acyl pantetheine [ 14 ] and on the much lower susceptibility of acyl pantetheine to3-oxidation than acyl CoA [ 14 ]. But this has been ruled out by the finding that palmitoyl-S-pantetheine did not serve as the substrate of the ketogenic reaction ( fig.7 ). 

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