Fatty adds camitine

Figure 19.5 Movement of fatty adds across inner mitochondrial membrane. The enzymes involved are designated as follows (1) fatty acyl-CoA synthetase (2) palmitoyl-CoA-camitine acyltransferase on the cytosol side of the inner mitochondrial membrane and (3) the same enzyme on the mitochondrial matrix side of the membrane.

Carnitine is used mainly for facilitating the transport of long-chain fatty adds into the mitochondria. As shown in Figure4.53, this transport system requires the participation of two different carnitine acyl transferases. One is located on the outside of the mitochondrial membrane, the other on the inner side. Once fatty acyl-camitine is inside the organelle, its carnitine is released. A separate transport system is used to transport this carnitine from the interior of the mitochondrion back to the cytoplasm for reuse. 

Carnitine is required for transport of longoxidative metabolism as well as in the formation of ketone bcidies, The concentration of free carnitine in muscle is about 4,0 mmol/kg. The concentration of carnitine bound to long-chain fatty adds (fatty acyl-camitine) is lower, about 0,2 mmol/kg. Short-chain fatty adds, including acetic, are also esterified to carnitine, but the functions of these complexes are not clear. There is some indication that keto forms of BCAAs (BCKAs) can also be esterified to carnitine. These complexes can then be transported into the mitochondria for complete oxidation of the BCKAs, The importance of this mode of BCKA transport is not dear (Takakura et ai., 1997). 

In order to be metabolized, long-chain fatty acids must first undergo conjugation to carnitine for transport by the acylcamitine-camitine carrier across the mitochondrial inner membrane [139]. Short-chain fatty acids enter the mitochondria through monocarboxylic acid transporters [139]. Studies were carried out to assess the effects cephaloridine, cephaloglydn and cephalexin on the mitochondrial oxidative metabolism of fatty adds such as butyrate and pahnitate [67]. 

Various pathways are employed for the degradation of branched-chain fatty acids, some of which arise from the metabolism of the branched-chain amino acids (see Leucine). Short-chain fatty adds are converted to their feitty acyl derivatives within the mitochondria, but long-chain fatty adds can be activated only by the endoplasmic reticulum and outer mi-tochondritd membrane. Long-chain acyl-CoA caimot penetrate the itmer mitochondrial membrane, and must be transported into the mitochondria as acyl-camitine (Fig. 3). 

CoASH and thus reforming the true immediate substrate for the oxidatioa According to this hypothesis, acyl carnitine, which is not a substrate for the enzymes of the oxidative process, is an admirable substrate for fatty acid degradation in intact mitochondrial systems. In addition, mitochondria depleted of their endogenous energy donors (ATP, GTP) are unable to oxidize add fatty acids unless ATP and carnitine are both present in the system. This observation clearly proves that acyl-CoA is formed outside of the inner mitochondrial membrane—i.e. outside of the oxidation compartment—and is transported to the inner compartment via the carnitine-linked transport mechanism. In agreement with these results an ATP-dependent thiokinase has been identified in the outer mitochondrial membrane, and an acyl-camitine transferase has been found in the inner mitochondrial membrane. 

---