Methylation of phosphatidylethanolamine

Yeast pathways for the synthesis of phosphatidylserine, phosphatidylethanolamine, and phosphatidylglycerol are similar to those in bacteria phosphatidylcholine is formed by methylation of phosphatidylethanolamine. 

Methionine is intimately related to lipid metabolism in the liver. Methionine deficiency is one of the causes of the fatty liver syndrome. Lack of methionine prevents the methylation of phosphatidylethanolamine to phosphatidylcholine, resulting in an ability by the liver to build and export very low density lipoprotein. The syndrome can be treated by the administration of choline, and for this reason, choline has often been referred to as the lipotropic factor. 

D. In the absence of dietary choline, PC can be synthesized de novo from glucose. The last step in this pathway involves methylation of phosphatidylethanolamine. 

Phosphatidylcholine can also be synthesized by the stepwise methylation of phosphatidylethanolamine. Methyl groups are transferred from 5-adenosyl-L-methionine and this pathway is a minor one in animals (20% of liver phosphatidylcholine synthesis but undetectable in other tissues Bell and Coleman, 1980) and plants (Moore, 1982). In those bacteria which contain phosphatidylcholine, it is made by stepwise methylation of phosphatidylethanolamine (Lennarz, 1970). 

These studies with bacteria indicate that, although animals and bacteria have a number of. similar pathways for phospholipid formation, there are several marked differences. Thus the major if not sole padiway for phosphatidylethanolamine (and phosphatidylserine) synthesis in bacteria is via CDP-diglyceride, while in animals this compound is formed from diglyceiide and CDP-ethanolamine (Keimedy and Weiss, 1956). Similarly, the major pathway for phosphatidylcholine sjmthesis in bacteria is via methylation of phosphatidylethanolamine, whereas in animals this compound is formed via diglyceride and CDP-choline (Kennedy and Weiss, 1956), as well as by methylation of phosphatidylethanolamine (Bremer and Greenberg, 1961). 

Mason JT, O Leary TJ. Effects of headgroup methylation and acyl chain length on the volume of melting of phosphatidylethanolamines. Biophys. J. 1990 58 277-281. 

Hay and Morrison (1971) later presented additional data on the fatty acid composition and structure of milk phosphatidylethanolamine and -choline. Additionally, phytanic acid was found only in the 1-position of the two phospholipids. The steric hindrance presented by the four methyl branches apparently prevents acylation at the 2-position. The fairly even distribution of monoenoic acids between the two positions is altered when the trans isomers are considered, as a marked asymmetry appears with 18 1 between the 1- and 2-positions of phosphatidylethanolamine, but not of phosphatidylcholine. Biologically, the trans isomers are apparently handled the same as the equivalent saturates because the latter have almost the same distribution. There are no appreciable differences in distribution of cis or trans positional isomers between positions 1 and 2 in either phospholipid. Another structural asymmetry observed is where cis, cis nonconjugated 18 2s are located mostly in the 2-position in both phospholipids. It appears that one or more trans double bonds in the 18 2s hinders the acylation of these acids to the 2-position. 

The major (salvage) pathways for the formation of phosphatidylcholine and ethanolamine are illustrated in Figure 19.16. Free (dietary) choline and etha-nolamine are converted to their CDP derivatives, which then react with diacyl-glycerol to form phosphatidylcholine and ethanolamine. In the lungs, another pathway forms dipalmitoyl phosphatidylcholine, a powerful surfactant. Phos-phatidylethanolamine may be methylated by S-adenosylmethionine (SAM see Chapter 20) to yield phosphatidylcholine. The reaction is catalyzed by two enzymes the first methyl group is transferred via phosphatidylethanolamine N-methyltransferase I. The other two methyl groups are transferred by phosphatidylethanolamine N-methyltransferase II. Some authorities believe that the two enzymes are identical. It has also been proposed that methylation of phospha-... 

Phosphatidylserine arises by an exchange of the ethanolamine residue of phosphatidylethanolamine for a seryl group. Decarboxylation of the serine of phosphatidylserine reforms phosphatidylethanolamine. Three successive methylation reactions convert phosphatidylethanolamine to phosphatidylcholine. 5-Adenosyl-methionine is the methyl-group donor (Chap. 15) (see Fig. 13-14). 

Triglyceride and phospholipid formation. This figure depicts the formation of triacylglycerol from a-glycerolphosphate and fatty-acyl CoA. The formation of phosphatidylethanolamine and phosphatidylcholine from scratch (i.e., from serine and methionine methyl groups) is also shown. The formation of phosphatidylcholine, starting with choline, is also depicted and is the major pathway for phosphatidylcholine synthesis. 

The conversion of phosphatidylethanolamine, a component of cell membranes, into phosphatidylcholine requires three methylations by three equivalents of SAM. (Biological cell membranes will be discussed in Section 26.4 the use of A -methyltetrahydrofolate as a biological methylating agent is discussed in more detail in Section 25.8.)... 

Choline is a common component of the diet bnt also can be synthesized in the human as part of the pathway for the synthesis of phospholipids (see Chapter 33). The only route for choline synthesis is via the sequential addition of three methyl groups from SAM to the ethanolamine portion of phosphatidylethanolamine to form phosphatidylcholine. Phosphatidylcholine is subsequently hydrolyzed to release choline or phosphocholine. Conversion of phosphatidylethanolamine to phosphatidylcholine occurs in many tissues, including liver and brain. This conversion is B6- and B 12-dependent. 

Haydn Pritchard, P., P.K. Chiang, G.L. Cantoni, and D.E. Vance. 1982. Inhibition of phosphatidylethanolamine V-methylation by 3 -deazaadenosine stimulates the synthesis of phosphatidylcholine via the CDP-choline pathway. J. Biol. Chem. 257(11) 6362-6367. 

Chaboaff, E., and A. S. Kbston The metabolism of aminoethylphosphoric acid, followed by means of the radioactive phosphorus isotope. J. biol. Chem. 134, 515—22 (1940). Chojnacki, T., T. Korzybski, and G. B. Ansell The methylation of natural and unnatural analogues of pjabelled phosphatidylethanolamine by brain and liver tissue. Biochem. J. 90, 18P—19P (1964). 

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