Carnitine acyltransferase II

Acyl coenzyme As are introduced into mitochondria following coenzyme A esterification in the cytoplasm. Mitochondrial entry depends upon a double membrane transport involving carnitine acyltransferases II and I. Excess acetyl CoA is used for KB synthesis. KBs are transported in the blood and ultimately metabolized via the Krebs cycle. KBs are necessary to provide energy to the brain during fasting, a true alternative substrate to glucose. 

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. 

This reaction is catalyzed by carnitine acyltransferase I on the outer membrane (fig. 18.21). A protein carrier in the inner mitochondrial membrane transfers the acyl-carnitine derivatives across the membrane. Once inside the mitochondria, the reaction is reversed by carnitine acyltransferase II to yield a fatty acyl-CoA (see fig. 18.21). Thus, at least two distinct pools of acyl-CoA occur in the cell, one in the cytosol and the other in the mitochondrion. 

Carnitine acyltransferase I, 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-carnitine then moves across the intermembrane space to a translocase enzyme, which, in turn, moves the acyl-carnitine to carnitine acyltransferase II, which exchanges the carnitine for Coenzyme A. 

Elaidoyl-CoA acyltransferase I elaidoyl-Carnitine transport elaidoyl-Carnitine acyltransferase II elaidoyl-CoA of fi oxidation (outside) (outside) (inside) (inside)... 

Carititine (3-hydroxy,4-AT-trimethylaminobutyric acid) has a central role in the transport of fatty acids across the mitochondrial membrane for p -oxidation. At the outer face of the outer mitochondrial membrane, carnitine acyltransferase I catalyzes the reaction shown in Figure 14.1, the transfer of fatty acids from coenzyme A (CoA) to form acyl carnitine esters that cross into the mitochondrial matrix. At the timer face of the inner mitochondrial membrane, carnitine acyltransferase II catalyzes the reverse reaction. 

The fact that the mitochondrial inner membrane is virtually impermeable to long-chain fatty acyl-CoA, while the fatty acid oxidative machinery is located inside the mitochondrial matrix, a space enclosed by the inner membrane, might create a serious problem for cellular energy production. The problem is solved by the development of a transmembrane carnitine-dependent transport system for the long-chain acyl residue of acyl-CoA. Catalyzed by carnitine acyltransferase I (CAT-I), which is attached to the inner surface of the mitochondrial outer membrane, fatty acyl-CoA is converted to fatty acyl-carnitine by replacing the CoA residue with carnitine (Figure 3). Fatty acyl-carnitine is transported across the mitochondrial inner membrane in exchange for a molecule of free carnitine by carnitine-acylcarnitine translocase. After arrival in the mitochondrial matrix, fatty acyl-carnitine is converted back to acyl-CoA by carnitine acyltransferase II (CAT-II), an enzyme located on the inner surface of the mitochondrial inner membrane. 

Fatty acids are activated to form acyl-CoA by acyl-CoA synthetase, an enzyme in the outer mitochrondrial membrane. Acyl-CoA then reacts with carnitine to form an acylcamitine derivative. Carnitine acyltrans-ferase I catalyzes this reaction. After acylcamitine is transported across the inner membrane by a carrier protein, it is subsequently reconverted to carnitine and acyl-CoA by carnitine acyltransferase II. 

The first step, catalyzed by the enzyme carnitine acyltransferase I, is the transfer of the fatty acyl group to carnitine, producing acylcarnitine and coenzyme A. Next a carrier protein located in the mitochondrial inner membrane transfers the acylcarnitine into the mitochondrial matrix. There carnitine acyltransferase II catalyzes the regeneration of fatty acyl CoA, which now becomes involved in the remaining reactions of p-oxidation. 

Acyl-Carnitine + CoASH <=> Acyl-CoA + Carnitine (catalyzed by Carnitine Acyltransferase II)... 

See also Fatty Acids, Carnitine Acyltransferase I, Carnitine Acyltransferase II, Acyl-CoAs, Acyl-Carnitine, CoASH, S-Adenosylmethionine and Biological Methylation... 

Carnitine acyltransferase I is an enzyme outside the mitochondrion that transfers the acyl group on coenzyme A to carnitine in the reaction below. This is the reversal of the reaction catalyzed by Carnitine acyltransferase II inside of the mitochondrion and is essential for transport of the acyl group into the mitochondrion. 

A translocase carries the acyl-carnitine into the mitochondria. Once inside the mitochondrial matrix, carnitine is replaced on the acyl group by CoASH in a reaction catalyzed by carnitine acyltransferase II. 

Carnitine acyltransferase II is an enzyme in the mitochondrial matrix that transfers the incoming acyl group on carnitine to coenzyme A in the reaction below. The reaction is the reversal of the reaction catalyzed by carnitine acyltransferase I outside of the mitochondrion. 

Carnitine acyltransferase I catalyzes exchange of CoA for carnitine to carry acyl group into mitochondrion. Carnitine acyltransferase II on inside of mitochondrion catalyzes reverse reaction to yield acyl-CoA and free carnitine (Figure 18,15)... 

Palmitoyl CoA combines with carnitine in a reaction catalysed by carnitine acyltransferase I (CAT I) located in the mitochondrial outer membrane, to form palmitoyl carnitine. The palmitoyl CoA is regenerated from palmitoyl carnitine by carnitine acyltransferase II (CAT II) located in the mitochondrial inner membrane. 

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