Biosynthesis and Metabolism of Choline

Phosphatidylcholine can be synthesized by the pathway shown in Figure 14.3. Decarboxylation of phosphatidylserine to phosphatidylethanolamine (cephalin) is followed by methylation in which S-adenosylmethionine is the methyl donor to yield successively the relatively rare mono- and dimethyl derivatives, then phosphatidylcholine.

Sequential removal of the fatty acids by phospholipase action results in the formation of lysolecithin (glycerophosphorylcholine), then hydrolysis to release choline. Acetylcholine is synthesized in neurons using acetyl CoA.

About 30% of dietary phosphatidylcholine is absorbed intact into the lymphatic system; the remainder is hydrolyzed to lysolecithin in the intestinal mucosa and to free choline in the liver. Free choline in the diet is largely metabolized by intestinal bacteria, forming trimethylamine, which is absorbed and excreted in the urine. Only about 30% of free choline is absorbed intact.

Choline can be used for synthesis of phosphatidylcholine by reaction between CDP-choline and diacylglycerol. Under normal conditions, the major pathway of phosphatidylcholine synthesis is by the incorporation of

Figure 14.3. Biosynthesis of choline, and acetylcholine. Relative molecular masses (Mr): choline, 104.2 (chloride, 139.6); and acetylcholine, 146.3 (chloride, 181.7). CoASH, free coenzyme A.

preformed choline rather than methylation of phosphatidylethanolamine. The activities of the two pathways are coordinately regulated, so that increased choline availability reduces the methylation of phosphatidylethanolamine, whereas decreased availability of preformed choline results in increased de novo synthesis (Lykidis and Jackowski, 2001).

As shown in Figure 14.4, choline catabolism involves two oxidation reactions to form betaine (trimethylglycine), followed by three successive deme-thylations. As discussed in Section 10.9.3, the remethylation of homocysteine to methionine catalyzed by the betaine-dependent methyltransferase

Figure 14.4. Catabolism of choline. Choline dehydrogenase, EC 1.1.99.1; betaine aldehyde dehydrogenase, EC 1.2.1.8; and homocysteine methyltransferase, EC 2.1.1.5. Relative molecular masses (Mr): choline, 104.2; betaine, 117.2; dimethylglycine, 102.2; methylglycine, 88.2; and glycine, 74.2. THF, tetrahydrofolate.

Figure 14.4. Catabolism of choline. Choline dehydrogenase, EC 1.1.99.1; betaine aldehyde dehydrogenase, EC 1.2.1.8; and homocysteine methyltransferase, EC 2.1.1.5. Relative molecular masses (Mr): choline, 104.2; betaine, 117.2; dimethylglycine, 102.2; methylglycine, 88.2; and glycine, 74.2. THF, tetrahydrofolate.

can maintain adequate concentrations of methionine in tissues other than the central nervous system when the activity of methionine synthetase is impaired because of vitamin B12 deficiency.

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