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Sexually Dimorphic Activation of Liver and Brain Phosphatidylethanolamine N-Methyltransferase by Dietary Choline Deficiency

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Abstract

Phosphatidylethanolamine N-methyltransferase (PEMT) activity was measured by a radioenzymatic assay in homogenates of brain and liver obtained from Sprague Dawley rats fed a choline-free or control (0.3 g/kg of choline chloride) diet for seven days. Choline deficiency increased PEMT activity in the liver of male rats by 34% but had no effect on hepatic PEMT in females. In contrast, brain PEMT activity was increased in brain of choline deficient females (by 49%) but was unaltered in males. Activation of the PE methylation pathway in female brain may constitute a compensatory mechanism to sustain PC synthesis during choline deficiency.

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REFERENCES

  1. Zeisel, S. H., and Blusztajn, J. K. 1994. Choline and human nutrition. Annu. Rev. Nutr. 14:269–296.

    Google Scholar 

  2. Bremer, J., and Greenberg, D. M. 1961. Methyl transferring enzyme system of microsomes in the biosynthesis of lecithin (phosphatidylcholine). Biochim. Biophys. Acta 46:205–216.

    Google Scholar 

  3. Bremer, J., and Greenberg, D. M. 1960. Biosynthesis of choline in vitro. Biochim. Biophys. Acta 37:173–175.

    Google Scholar 

  4. Bremer, J., Figard, P. H., and Greenberg, D. M. 1960. The biosynthesis of choline and its relation to phospholipid metabolism. Biochim. Biophys. Acta 43:477–488.

    Google Scholar 

  5. Blusztajn, J. K., Zeisel, S. H., and Wurtman, R. J. 1979. Synthesis of lecithin (phosphatidylcholine) from phosphatidylethanolamine in bovine brain. Brain Res. 179:319–327.

    Google Scholar 

  6. Mozzi, R., and Porcellati, G. 1979. Conversion of phosphatidylethanolamine to phosphatidylcholine in rat brain by the methylation pathway. FEBS Lett. 100:363–366.

    Google Scholar 

  7. Crews, F. T., Hirata, F., and Axelrod, J. 1980. Phospholipid methyltransferase asymmetry in synaptosomal membranes. Neurochem. Res. 5:983–990.

    Google Scholar 

  8. Crews, F. T., Hirata, F., and Axelrod, J. 1980. Identification and properties of methyltransferase that synthesize phosphatidylcholine in rat brain synaptosomes. J. Neurochem. 34:1491–1498.

    Google Scholar 

  9. Blusztajn, J. K., and Wurtman, R. J. 1981. Choline biosynthesis by a preparation enriched in synaptosomes from rat brain. Nature 290:417–418.

    Google Scholar 

  10. Crews, F. T., Calderini, G., Battistella, A., and Toffano, G. 1981. Age dependent changes in the methylation of rat brain phospholipids. Brain Res. 229:256–259.

    Google Scholar 

  11. Blusztajn, J. K., Zeisel, S. H., and Wurtman, R. J. 1985. Developmental changes in the activity of phosphatidylethanolamine N-methyltransferases in rat brain. Biochem. J. (Lond) 232:505–511.

    Google Scholar 

  12. Lakher, M., and Wurtman, R. J. 1987. In vivo synthesis of phosphatidylcholine in rat brain via the phospholipid methylation pathway. Brain Res. 419:131–140.

    Google Scholar 

  13. Bjornstad, P., and Bremer, J. 1966. In vivo studies on pathways for the biosynthesis of lecithin in the rat. J. Lipid Res. 7:38–45.

    Google Scholar 

  14. Sundler, R., and Akesson, B. 1975. Regulation of phospholipid biosynthesis in isolated rat hepatocytes. J. Biol. Chem. 250:3359–3367.

    Google Scholar 

  15. Ridgway, N. D., Yao, Z., and Vance, D. E. 1989. Phosphatidylethanolamine levels and regulation of phosphatidylethanolamine N-methyltransferase. J. Biol. Chem. 264:1203–1207.

    Google Scholar 

  16. Glenn, J. L., and Austin, W. 1971. The conversion of phosphatidyl ethanolamines to lecithins in normal and choline-deficient rats. Biochim. Biophys. Acta 231:153–160.

    Google Scholar 

  17. Cui, Z., and Vance, D. E. 1996. Expression of phosphatidylethanolamine N-methyltransferase-2 is markedly enhanced in long term choline-deficient rats. J. Biol. Chem. 271:2839–2843.

    Google Scholar 

  18. Hoffman, D. R., Haning, J. A., and Cornatzer, W. E. 1981. Effect of a methyl-deficient diet on rat liver phosphatidylcholine biosynthesis. Can. J. Biochem. 59:543–550.

    Google Scholar 

  19. Schneider, W. J., and Vance, D. E. 1978. Effect of choline deficiency on the enzymes that synthesize phosphatidylcholine and phosphatidylethanolamine in rat liver. Eur. J. Biochem. 85:181–187.

    Google Scholar 

  20. Blusztajn, J. K., and Wurtman, R. J. 1983. Choline and cholinergic neurons. Science 221:614–620.

    Google Scholar 

  21. Blusztajn, J. K., Liscovitch, M., and Richardson, U. I. 1987. Synthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line. Proc. Natl. Acad. Sci. USA. 84:5474–5477.

    Google Scholar 

  22. Lee, H.-C., Fellenz-Maloney, M.-P., Liscovitch, M., and Blusztajn, J. K. 1993. Phospholipase D-catalyzed hydrolysis of phosphatidylcholine provides the choline precursor for acetylcholine synthesis in a human neuronal cell line. Proc. Natl. Acad. Sci. USA 90:10086–10090.

    Google Scholar 

  23. Zeisel, S. H., Zola, T., DaCosta, K.-A., and Pomfret, E. A. 1989. Effect of choline deficiency on S-adenosylmethionine and methionine concentrations in rat liver. Biochem. J. 259:725–729.

    Google Scholar 

  24. Hoffman, D. R., Uthus, E. O., and Cornatzer, W. E. 1980. Effect of diet on choline phosphotransferase, phosphatidylethanolamine methyltransferase and phosphatidyldimethylethanolamine methyltransferase in liver microsomes. Lipids 15:439–446.

    Google Scholar 

  25. Cui, Z., Vance, J. E., Chen, M. H., Voelker, D. R., and Vance, D. E. 1993. Cloning and expression of a novel phosphatidylethanolamine N-methyltransferase. A specific biochemical and cytological marker for a unique membrane fraction in rat liver. J. Biol. Chem. 268:16655–16663.

    Google Scholar 

  26. Wecker, L., and Trommer, B. A. 1984. Effects of chronic (dietary) choline availability on the transport of choline across the blood-brain barrier. J. Neurochem. 43:1762–1765.

    Google Scholar 

  27. Oldendorf, W. H., Crane, P. D., Braun, L. D., Wade, L. A., and Diamond, J. M. 1983. Blood-brain barrier transport of basic amino acids is selectively inhibited at low pH. J. Neurochem. 40:797–800.

    Google Scholar 

  28. Cornford, E. M., Braun, L. D., and Oldendorf, W. H. 1978. Carrier mediated blood-brain barrier transport of choline and certain choline analogs. J. Neurochem. 30:299–308.

    Google Scholar 

  29. Braun, L. D., Cornford, E. M., and Oldendorf, W. H. 1980. Newborn rabbit blood-brain barrier is selectively permeable and differs substantially from the adult. J. Neurochem. 34:147–152.

    Google Scholar 

  30. Growdon, J. H., and Logue, M. 1982. Choline, HVA, and 5-HIAA levels in cerebrospinal fluid of patients with Alzheimer's disease. Pages 35–43, in Corkin, S., Davis, K. L., Growdon, J. H., Usdin, E. and Wurtman, R. J. (eds) Alzheimer's disease: a report of progress in research, Raven Press, New York.

    Google Scholar 

  31. Okuyama, S., and Ikeda, Y. 1988. Determination of acetylcholine and choline in human cerebrospinal fluid using high-performance liquid chromatography combined with an immobilized enzyme reactor: Ageing-induced change of acetylcholine level. J. Chromatogr. 431:389–394.

    Google Scholar 

  32. Klein, J., Köppen, A., and Löffelholz, K. 1990. Small rises in plasma choline reverse the negative arteriovenous difference of brain choline. J. Neurochem. 55:1231–1236.

    Google Scholar 

  33. Klein, J., Köppen, A., and Löffelholz, K. 1991. Uptake and storage of choline by rat brain: Influence of dietary choline supplementation. J. Neurochem. 57:370–375.

    Google Scholar 

  34. Cohen, B. M., Renshaw, P. F., Stoll, A. L., Wurtman, R. J., Yurgelun-Todd, D., and Babb, S. M. 1995. Decreased brain choline uptake in older adults—An in vivo proton magnetic resonance spectroscopy study. JAMA 274:902–907.

    Google Scholar 

  35. Toran-Allerand, C. D., Miranda, R. C., Bentham, W. D. L., Sohrabji, F., Brown, T. J., Hochberg, R. B., and MacLusky, N. J. 1992. Estrogen receptors colocalize with low-affinity nerve growth factor receptors in cholinergic neurons of the basal forebrain. Proc. Natl. Acad. Sci. USA 89:4668–4672.

    Google Scholar 

  36. Gibbs, R. B. 1996. Expression of estrogen receptor-like immunoreactivity by different subgroups of basal forebrain cholinergic neurons in gonadectomized male and female rats. Brain Res. 720:61–68.

    Google Scholar 

  37. Blusztajn, J. K., Lopez Gonzalez-Coviella, I., Logue, M., Growdon, J. H., and Wurtman, R. J. 1990. Levels of phospholipid catabolic intermediates, glycerophosphocholine and glycerophosphoethanolamine, are elevated in brains of Alzheimer's disease but not of Down's syndrome patients. Brain Res. 536:240–244.

    Google Scholar 

  38. Nitsch, R. M., Blusztajn, J. K., Pittas, A. G., Slack, B. E., Growdon, J. H., and Wurtman, R. J. 1992. Evidence for a membrane defect in Alzheimer disease brain. Proc. Natl. Acad. Sci. USA 89:1671–1675.

    Google Scholar 

  39. Wurtman, R. J., Blusztajn, J. K., and Maire, J.-C. 1985. “Autocannibalism” of choline-containing membrane phospholipids in the pathogenesis of Alzheimer's disease. Neurochem. Int. 7:369–372.

    Google Scholar 

  40. Bowen, D. M., Smith, C. B., White, P., and Davison, A. N. 1976. Neurotransmitter related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain 99:459–496.

    Google Scholar 

  41. Bierer, L. M., Haroutunian, V., Gabriel, S., Knott, P. J., Carlin, L. S., Purohit, D. P., Perl, D. P., Schmeidler, J., Kanof, P., and Davis, K. L. 1995. Neurochemical correlates of dementia severity in Alzheimer's disease: Relative importance of the cholinergic deficits. J. Neurochem. 64:749–760.

    Google Scholar 

  42. McGeer, P. L., McGeer, E. G., Suzuki, J., Dolman, C. E., and Nagai, T. 1984. Aging, Alzheimer's disease, and the cholinergic system of the basal forebrain. Neurology 34:741–745.

    Google Scholar 

  43. Perry, E. K., Tomlinson, B. E., Blessed, G., Bergman, K., Gibson, P. H., and Perry, R. H. 1978. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br. Med. J. 2:1457–1459.

    Google Scholar 

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Johnson, P.I., Blusztajn, J.K. Sexually Dimorphic Activation of Liver and Brain Phosphatidylethanolamine N-Methyltransferase by Dietary Choline Deficiency. Neurochem Res 23, 583–587 (1998). https://doi.org/10.1023/A:1022470301550

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