PE methylation pathway

The CDP-choline pathway to PC (Figure 6.1) occurs in a number of tissues, but the PE methylation pathway (Figure 6.2) occurs mainly in the liver and accounts... 

All nucleated cells contain PC and utilize the CDP-choline pathway. Thus, it was not obvious why the alternative pathway for PC synthesis, the PE methylation pathway (Fig. 4), survived during evolution. Nor was it obvious why PE methyltransferase (PEMT) activity is essentially a liver-specific enzyme whereas 2% or less of the hepatic PEMT activity is found in other tissues. In addition to producing PC, PEMT generates three... 

FIGURE 6.2 Phosphatidylcholine (PC) synthesis by the CDP-ethanolamine pathway. Structures of ethanolamine and choline. The nucleotide moiety S-adenosyl methionine (SAM) is required to transfer the methyl group of methionine to phosphatidylethanolamine (PE) to form PC. In the process, SAM is converted to S-adenosyl homocysteine (SAH). The nitrogen atom of PC has four covalent bonds and is called a quaternary amine. It bears a positive charge that is not influenced by changes in the pH of the surroimding fluids. The PE methyltransferase pathway of PC synthesis occurs only in the liver. 

An alternative pathway for PC biosynthesis, of quantitative significance only in liver, is the conversion of PE to PC via PE methylation (Fig. 4). This pathway was first observed... 

The methylation pathway for PC synthesis in castor bean endosperm was examined by Moore (1976). Activity was found mainly in the ER but also in mitochondria. The pH optimum for methylation was found to be 9, and the Km for 5-adenosylmethionine was 31 itM. Moore (1976) verified the findings of Marshall and Kates (1973, 1974) that PE was a very poor substrate and that DMPE was the best acceptor. Moore (1976) determined that the activity of the methylation reaction under optimal conditions was only that of PC formation from CDP-choUne. In spite of these results in vitro it should be noted that, when dimethylethanolamine is supplied to aging potato discs, there is no indication of its utilization for PC synthesis DMPE is the major product, and PC synthesis is inhibited (Waring and Laties, 1977). 

A minor pathway to synthesize PC, which is mainly active in liver cells, utilizes the enzyme phosphatidylethanolamine-A-methyltransferase (PEMT), which converts phosphatidylethanolamine (PE) to PC by the subsequent transfer of three methyl groups from S-adenosylmethionine (Vance et al, 1997). The PEMT pathway, which links PE synthesis to PC, was found to be critical for PC homeostasis in the Uver dining choline deficiency (Walkey et al, 1997). 

Bacteria generally do not contain PC but Rhodobacter sphaeroides and some other bacteria make PC by the methylation of PE. Interestingly, this methyltransferase is a soluble protein that has virtually no homology to PEMT or the yeast enzymes (V. Arondel, 1993). Also, in some bacteria, such as Sinorhizobium meliloti, a novel choline-dependent pathway was discovered in which choline reacts with CDP-DG to form PC (O. Geiger, 2003). 

Synlhesis of these previous methyl- and ethyl-branched PEs has been suceess-ful using different approaches in the preparation of the respective a,co-diene monomers. However, an easy and very productive pathway for these monomers is based on the double alkylation of ethyl acetoacetate" " " " " or diethyhnalonate." " ... 

Both Kennedy pathway through CDP-choline and successive methylation from PE to PC catalyzed by A-methyltransferases [2, 3] play equal roles in... 

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