Camitine acyltransferases

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.

Palmitoyl-CoA-camitine acyltransferase is rate controlling in fatty acid degradation. Its effector is malonyl-CoA, which inhibits its activity. 

This reaction is catalyzed by palmitoyl-CoA-camitine acyltransferase and does not require ATP. The acyl-CoA is sufficiently "activated" to be able to react with carnitine. 

Because insulin normally inhibits lipolysis, a diabetic has an extensive lipolytic activity in the adipose tissue. As is seen in Table 21.4, plasma fatty acid concentrations become remarkably high. /3-Oxidation activity in the liver increases because of a low insulin/glucagon ratio, acetyl-CoA carboxylase is relatively inactive and acyl-CoA-camitine acyltransferase is derepressed. /3-Oxidation produces acetyl-CoA which in turn generates ketone bodies. Ketosis is perhaps the most prominent feature of diabetes mellitus. Table 21.5 compares ketone body production and utilization in fasting and in diabetic individuals. It may be seen that, whereas in the fasting state ketone body production is roughly equal to excretion plus utilization, in diabetes this is not so. Ketone bodies therefore accumulate in diabetic blood. 

Derrick, J. Ramsay, R. (19 9) Biochem. 7, 262 801-806. L-Camitine acyltransferase in intact peroxisomes is inhibited by malonyl-CoA. 

Gerbling H, Gandour RD, Moore TS, Gerhardt B. Camitine-acyltransferase activity in plant mitochondria. In Quinn PJ, Harwood JL, editors. Plant Lipid Biochemistry, Structure, Function and Utilization. London Portland Press, 1990 181... 

In the third and final step of the carnitine shuttle, the fatty acyl group is enzymatically transferred from carnitine to intramitochondrial coenzyme A by carnitine acyltransferase II. This isozyme, located on the inner face of the inner mitochondrial membrane, regenerates fatty acyl-CoA and releases it, along with free carnitine, into the matrix (Fig. 17-6). Carnitine reenters the intermembrane space via the acyl-camitine/car-nitine transporter. 

Carnitine acyltransferase 1, which is located on the outer mitochondrial membrane, transfers the fatty acyl group from fatty acyl-CoA to the hydroxyl (OH) group of carnitine. The acyl-camitine then moves across the intermembrane space to a translocase enzyme, which, in turn, moves the acyl-carnitine to carnitine acyltransferase 11, which exchanges the carnitine for Coenzyme A. 

Carnitine is used mainly for facilitating the transport of long-chain fatty adds into the mitochondria. As shown in Figure 4.53, this transport system requires the participation of two different carnitine acyltransferases. One is located on the outside of the mitochondrial membrane, the other on the iimer 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 linked to acyl groups transported into the mitochondria for oxidation (Figure 18.15). Acyl-CoAs in the cytoplasm are converted to acyl-camitine derviatives by action of carnitine acyltransferase I on the outer portion of the mitochondrial inner membrane. A translocase carries the acyl-carnitine into the mitochondria. Once inside the mitochondrial matrix, carnitine is replaced on the acyl group by CoASH. The acyl-CoA then is free to go through oxidation or elongation. 

Carnitine acyltransferases are involved in the transfer of acyl groups from acyl-CoAs to L-camitine i.e. in the reversible conversion of acyl-CoA into acylcamitine. Th enzymes have a wide and overlapping chain-length specificity and a range of cellular loc zations and metabolic functions. The best characterized carnitine acyltransferases are the mitochondrial carnitine palmitoyltransferases (CPT EC 2.3.1.21) flie CPTI and CPTII. The latest progress and current view of the stmctural, functional, regulatory and... 

Figure 4. Effect of L-camitine addition on glycerol-3-phosphate acyltransferase specific activity in highly purified mitochondrial fractions (HPMF). Values are expressed as nmol of palmitoyI-glycerol-3-pho phate (] m-G3P) synthesized/min per mg of protein, (open circles) HPMF alone (open squares) addition of 0.4mM L-camitine or (open triangles) 0.4 mM L-camitine + SOpM malonyl-CoA. Results are representative of four independent experiments.

---