Mitochondria fatty acid transport into, regulation

Transsport of fatty adds into the mitochondrion is regulated by a mechanism that plays a major role in controlling the overall rate of oxidation of fatty acids. This mechanism is in "communication" with the pathw ay for fatty acid synthesis. The fatty acid transport system is sensitive to the concentration of one fatty acid synthesis intermediate, malonyl-CoA. 

Acyl-CoA synthetase activity towards long-chain fatty-acid substrates is present in the outer mitochondrial membrane. However, fatty acyl-CoAs do not readily traverse biological membranes such as the inner mitochondrial membrane. A highly sophisticated transport system has evolved to allow tight regulation of fatty-acid entry into the mitochondrion (Figure 2). Carnitine palmitoyl transferase 1 (CPTl), located on the inner aspect of the... 

One enzyme regulated by AMPK is acetyl-CoA carboxylase, which produces malonyl-CoA, the first intermediate committed to fatty acid synthesis. Malonyl-CoA is a powerful inhibitor of the enzyme carnitine acyl-transferase I, which starts the process of ]3 oxidation by transporting fatty acids into the mitochondrion (see Fig. 17-6). By phosphorylating and inactivating acetyl-CoA carboxylase, AMPK inhibits fatty acid synthesis while relieving the inhibition (by malonyl-CoA) of )3 oxidation (Fig. 23-37). 

Acylcarnitine can cross only the inner mitochondrial membrane on a countertransport system that takes in acylcarnitine in exchange for free carnitine being returned to the inter-membrane space. Once inside the mitochondrial inner membrane, acylcarnitine transfers the acyl group onto CoA ready to undergo -oxidation. This counter-transport system provides regulation of the uptake of fatty acids into the mitochondrion for oxidation. As long as there is free CoA available in the mitochondrial matrix, fatty acids can be taken up and the carnitine returned to the outer membrane for uptake of more fatty acids. However, if most of the CoA in the mitochondrion is acylated, then there is no need for further fatty uptake immediately and, indeed, it is not possible. 

---