Palmitoyl transferase

The steps in the subsequent utilization of muscle LCFAs may be summarized as follows. The free fatty acids, liberated from triglycerides by a neutral triglyceride lipase, are activated to form acyl CoAs by the mediation of LCFAcyl-CoA synthetase which is situated on the outer mitochondrial membrane. The next step involves carnitine palmitoyl transferase I (CPT I, see Figure 9) which is also located on the outer mitochondrial membrane and catalyzes the transfer of LCFAcyl residues from CoA to carnitine (y-trimethyl-amino-P-hydroxybutyrate). LCFAcyl... 

Carnitine palmitoyl transferase (CPT) deficiencies are commonly associated with myoglobinuria after prolonged exercise typically patients are young men and... 

As soon as Ras sticks to the plasma membrane another lipid anchor is attached to it. A putative palmitoyl transferase which is assumed to reside in the... 

Carnitine acyltransfefase-I (CAT-1) and carnitine acyltran erase-2 (CAT-2) are also refened to as carnitine palmrtoyl transferase-1 (CPT-1) and carnitine palmitoyl transferase-2 (CPT-2). The carnitine transport system is most important for allowing long-chain fatty acids to enter into the mitochondria. 

Figure 7.11 Mechanism of transport of long-chain fatty adds across the inner mitochondrial membrane as fatty acyl carnitine. CRT is the abbreviation for carnitine palmitoyl transferase. CPT-I resides on the outer surface of the inner membrane, whereas CPT-II resides on the inner side of the inner membrane of the mitochondria. Transport across the inner membrane is achieved by a carrier protein known as a translocase. FACN - fatty acyl carnitine, CN - carnitine. Despite the name, CRT reacts with long-chain fatty acids other than palmitate. CN is transported out of the mitochondria by the same translocase.

Despite the fact that cestodes appear to be capable of considerable lipid synthesis, the actual pathways and enzyme systems involved have been little studied. Sphingomyelin synthesis has been investigated in H. diminuta (37), where it probably involves the same five-step pathway thought to occur in vertebrates involving the enzymes serine palmitoyl-transferase,... 

In animals, the production of CO2 from [ Cjpalmitate or octanoate is not consistendy affected by riboflavin deficiency, possibly as a result of increased activity of carnitine palmitoyl transferase, which is more a response to food deprivation than to riboflavin deficiency. However, the production of C02 from [ C] adipic acid is significandy reduced, and responds rapidly (with some overshoot) to repletion with the vitamin. It has been suggested that the abiUty to metabolize a test dose of [ Cjadipic acid may provide a sensitive means of investigating ribodavin nutritional status in human beings (Bates, 1989, 1990). 

The final step in the acylation of Ras is the formation of a palmitoylester bond with a cysteine. Palmitoylation is reversible and could be subject to regulation. In yeast cells, where the protease that removes the COOH-terminal AAX sequence has been deleted by mutation, Ras can not be palmitoylated. In these cells Ras has lost its orientation and ends up in the interior of the cell, rather than at the plasma membrane. Therefore it is thought that farnesylation may target Ras quite indiscriminately to all kinds of cellular membranes, including endoplasmic membranes, and that only palmitoylation traps Ras in the plasma membrane, where the palmitoyl transferase is localized. 5... 

Fig. 3.15 FTase transfers the farnesyl group from farnesyl diphosphate (FPP) to the SH group of a cysteine near the COOH-terminus of the protein. The COOH-terminal tripeptide, AAX (A is an aliphatic amino acid and X is Val-Leu-Ser, or any other amino-acid residue), is removed by a protease. Subsequently, a methyl transferase donates the methyl (CH3) group from S-adenosylmethionine (SAM) to the COOH-terminal Sfarnesylated cysteine. The final step is the attachment of palmrtoyl groups to the cysteines near the farnesylated, carboxymethylated-terminus by a specific palmitoyl transferase.

L-cycloserine is an inhibitor of serine palmitoyl transferase (85), the first committed step in GSL biosynthesis. However, because this inhibitor prevents the synthesis of the highly bioactive ceramide, an interpretation of GSL depletion is equivocal. 

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. 

Malonyl CoA (-) carnitine palmitoyl transferase I (decreasing -oxidation). 

CPT-I deficiency (liver and muscle types) 255120 600528 601987 Carnitine palmitoyl transferase I <1 100,000 Liver disease, hypotonia, renal tubular acidosis AFLP... 

CPT-II deficiency 600649 600650 Carnitine palmitoyl transferase II <1 100,000 Cardiomyopathy, liver disease, congenital anomalies. Adult onset myopathy. ... 

J. D. McGarry, S. E. Mills, C. S. Long, and D.W. Foster, Observations on the affinity for carnitine and malonyl-CoA sensitivity of carnitine palmitoyl transferase I in animal and human tissues. Demonstration of the presence of malonyl-CoA in non-hepatic tissues of the rat, Biochem J 214, 21-28 (1983). 

This hepatomegaly is correlated to PPARa activation of acyl-CoA oxidase (AOX), the first enzyme of peroxisomal /3-oxidation of fatty acids and a gene with a PPRE in its promoter region14. In addition, hepatic mitochondrial /3-oxidation and microsomal w-oxidation of fatty acids are increased, as a direct result of PPARa activation of mRNA of specific enzymes associated with these pathways (carnitine palmitoyl transferase I and cytochrome P4504A, respectively). Activation of fatty acid oxidation by these three pathways would lead to enhanced fatty acid oxidation, given the appropriate substrate. PPARa has also been shown to enhance delivery of fatty acids to the oxidizing systems (Fig. 3). 

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 acyltransferase (also called carnitine palmitoyl transferase)... 

As noted above, there have been reports that link some cases of APLP with a defect in fatty acid metabolism in the fetus. These include fetal deficiencies of long chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD), carnitine-palmitoyl transferase 1 (CPT 1), and medium chain acyl-coenzyme A dehydrogenase (MCAD). The mechanism by which defective fetal fatty acid oxidation causes maternal illness is not known. However, since the fetus uses primarily glucose metabolism for its energy needs, it is likely that toxic products from the placenta, which does use fatty acid oxidation, cause the maternal liver failure. 

---