Effect of vitamin B12 deficiency on phosphatidylethanolamine methylation in rat liver.

1. In vitamin B12 deficiency the activity of tetrahydropteroylglutamate methyltransferase (EC 2.1.1.13) is depressed and the synthesis of methionine is reduced. Because the methyl group of methionine is largely utilized for the methylation of phosphatidylethanolamine, we investigated the effects of vitamin B12 deficiency on phosphatidylcholine synthesis. 2. The incorporation of injected [14C]formaldehyde into liver phosphatidylcholine was reduced by approximately 50% in vitamin B12-deficient rats. Also the corresponding incorporation of 5-[14C]methyltetrahydrofolic acid tended to decrease. The findings are consistent with a lower conversion of these precursors to methionine. 3. The effect of the deficient methyl-group supply on phosphatidylcholine synthesis was also investigated by the injection of [14C]ethanolamine. The amount (%) of lipid-14C recovered in phosphatidylcholine was significantly reduced in vitamin B12 deficiency. 4. Chemical analysis of liver phospholipids showed that the vitamin B12-deficient rats had a higher proportion of phosphatidylethanolamine and a lower proportion of phosphatidylcholine, indicating that the impaired synthesis of phosphatidylcholine by methylation leads to changes in membrane phospholipid composition.