Choline redistribution during adaptation to choline deprivation.

Choline is an important nutrient for mammals. Choline can also be generated by the catabolism of phosphatidylcholine synthesized in the liver by the methylation of phosphatidylethanolamine by phosphatidylethanolamine N-methyltransferase (PEMT). Complete choline deprivation is achieved by feeding Pemt(-)(/)(-) mice a choline-deficient diet and is lethal due to liver failure. Mice that lack both PEMT and MDR2 (multiple drug-resistant protein 2) successfully adapt to choline deprivation via hepatic choline recycling. We now report another mechanism involved in this adaptation, choline redistribution. Normal levels of choline-containing metabolites were maintained in the brains of choline-deficient Mdr2(-)(/)(-)/Pemt(-)(/)(-) mice for 90 days despite continued choline consumption via oxidation. Choline oxidase activity had not been previously detected in the brain. Plasma levels of choline were also maintained for 90 days, whereas plasma phosphatidylcholine levels decreased by >60%. The injection of [(3)H]choline into Mdr2(-)(/)(-)/Pemt(-)(/)(-) mice revealed a redistribution of choline among tissues. Although CD-Pemt(-)(/)(-) mice failed to adapt to choline deprivation, choline redistribution was also initiated in these mice. The data suggest that adaptation to choline deprivation is not restricted to liver via choline recycling but also occurs in the whole animal via choline redistribution.