Sphingomyelin metabolism in rat liver after chronic dietary replacement of choline by N-aminodeanol.

Sphingomyelin (SM) is a structural element of cell membranes and lipoproteins, and participates in signal transduction. To determine whether a choline analog (N-amino-N,N-dimethylaminoethanol, N-aminodeanol, NADe) can be substituted for choline in the SM of liver, rats (male, Sprague-Dawley-derived) were fed a diet that was low in choline and methionine, and contained 35.5 mmol of NADe/kg. After 18 months, liver plasma membranes and microsomes contained 48.9 +/- 3.6 and 93.6 +/- 6.9 nmol/mg protein of phosphatidyl-NADe, respectively, and 3.2 +/- 0.2 and 3.5 +/- 0.1 nmol/mg protein of ceramide phospho-NADe. The SM content of microsomes from NADe-fed rats was about one-third lower than for the control, and phosphatidylcholine (PC) was reduced by < 10%; there was also a small decrease in PC, but not SM, in plasma membranes. In vitro assays of enzymes involved in SM metabolism found no change in PC:ceramide cholinephosphotransferase, but the NADe-fed animals had higher phosphatidylethanolamine:ceramide ethanolaminephosphotransferase activity, greater incorporation of methyl groups from [methyl-3H]-S-adenosyl methionine into SM, and a lower neutral sphingomyelinase activity. These results show that NADe-fed rats from considerable amounts of ceramide phospho- and phosphatidyl-NADe; however, liver plasma membranes retain relatively normal levels of PC and SM, perhaps due to increases in the de novo pathway for SM synthesis and decreases in SM turnover.