Phosphatidylcholines (PC) are a class of phospholipids that incorporate a phosphocholine headgroup into a diacylglycerol backbone. They are the most abundant phospholipid in eukaryotic cell membranes and has both structural and signalling roles. In eukaryotes, there exist two phosphatidylcholine biosynthesis pathways: the Kennedy pathway and the methylation pathway. The Kennedy pathway begins with the direct phosphorylation of free choline into phosphocholine followed by conversion into CDP-choline and subsequently phosphatidylcholine. It is the major synthesis route in animals. The methylation pathway involves the 3 successive methylations of phosphoethanolamine to form phosphocholine which is then funnelled into the Kennedy pathway to make phosphatidylcholine. In plants, phosphatidylcholine biosynthesis is implemented using a mix between the two pathways. An alternative of the methylation pathway uses phosphatidylethanolamine as a starting compound, but no enzyme has been found in Arabidopsis to catalyze the first methylation to form phosphatidyl-N-methylethanolamine. Many enzymes involved in this pathway are localized to the cell membrane but are not drawn as such for clarity. Instead, they are indicated with a dark green colour and appear to be free floating in the cytosol. The first reaction of the Kennedy pathway involves the membrane-localized enzyme choline/ethanolamine kinase catalyzing the conversion of choline into phosphocholine. Second, choline-phosphate cytidylyltransferase catalyzes the conversion of phosphocholine to CDP-choline. Last, choline/ethanolaminephosphotransferase, localized to the cell membrane, catalyzes phosphatidylcholine biosynthesis from CDP-choline. It requires either magnesium or manganese ions as cofactors. Note that phosphatidylcholine can be converted to either phosphocholine by a non-specific phospholipase or converted to choline by phospholipase D. Phosphocholine can also be converted to choline via phosphoethanolamine/phosphocholine phosphatase. The methylation pathway begins with serine decarboxylase catalyzing the biosynthesis of ethanolamine from serine. It requires pyridoxal 5'-phosphate as a cofactor. Next, choline/ethanolamine kinase, localized to the cell membrane, catalyzes the conversion of ethanolamine to phosphoethanolamine. Phosphoethanolamine N-methyltransferase (PEAMT), located in the cytosol, then catalyzes three sequential N-methylation steps to convert phosphoethanolamine to phosphocholine. PEAMT uses S-adenosyl-L-methionine as a methyl donor. Phosphocholine then enters the Kennedy pathway. Alternatively, in a subpathway parallel to the Kennedy pathway, phosphoethanolamine can be converted into phosphatidylethanolamine. Phosphatidylethanolamine is also synthesized from phosphatidylserine in the endoplasmic reticulum by phosphatidylserine decarboxylase. Note that phosphatidylethanolamine can be converted to either phosphoethanolamine by a non-specific phospholipase or converted to ethanolamine by phospholipase D. The two methylated intermediates N-methylethanolamine phosphate and N-dimethylethanolamine phosphate can also undergo reactions parallel to the Kennedy pathway to form the methylated intermediates of phosphatidylethanolamine (otherwise catalyzed by phosphatidyl-N-methylethanolamine N-methyltransferase, localized to the endoplasmic reticulum membrane, to form phosphatidylcholine).

Phosphatidylcholine Biosynthesis References