Advertisement

Effects of Exogenous L-Dopa on the Metabolism of Methionine and S-Adenosylmethionine in the Brain

  • R. J. Wurtman
  • L. A. Ordonez
Part of the Monographien aus dem Gesamtgebiete der Psychiatrie book series (PSYCHIATRIE, volume 18)

Abstract

The catecholamines dopamine, norepinephrine, and epinephrine are metabolized by oxidative deamination and by O-methylation. This latter pathway is catalyzed by the enzyme catechol-O-methyl-transferase (1); it utilizes S-adenosyl-methionine (SAMe) as the methyl donor (Fig. 1), and its products are, for the most part, methylated on the metahydroxyl group. The catecholamines themselves are formed within only a few specific tissues in the body (21). These include a relatively small number of brain neurons, postganglionic sympathetic neurons, adrenomedullary chromaffin cells, and interneurons within sympathetic ganglia. The catechol-amines can be O-methylated within their cells of origin, within synapses, or, after secretion into the blood stream, within the liver, kidneys, and other organs.

Keywords

Methionine Adenosyltransferase Methionine Concentration Postganglionic Sympathetic Neuron Homocysteine Methyltransferase Methyl Group Metabolism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Axelrod, J., Tomchick, R.: Enzymatic O-methylation of epinephrine and other catechols. J. biol. Chem. 233, 702 (1958)PubMedGoogle Scholar
  2. 2.
    Baldessarini, R.J.: Alterations in tissue levels of S-adenosylmethionine. Biochem. Pharmacol. 15, 741(1966)PubMedCrossRefGoogle Scholar
  3. 3.
    Bartholini, G., Pletscher, A.: Cerebral accumulation and metabolism of C14-dopa after selective inhibition of peripheral decarboxylase. J. Pharmacol, exp. Ther. 161 14(1968)Google Scholar
  4. 4.
    Bridgers, W.F.: Serine transhydroxymethylase in developing mouse brain. J. Neurochem. 15, 1325(1968)PubMedCrossRefGoogle Scholar
  5. 5.
    Broderich, D.S., Candland, K.L., North, J.A., Mangum, J.H.: The isolation of serine transhydroxymethylase from bovine brain. Arch. Biochem. 148, 196 (1972)CrossRefGoogle Scholar
  6. 6.
    Calne, D.B., Karoum, F., Ruthven C.R.J., Sandler, M.: The metabolism of orally administered L-dopa in Parkinsonism. Brit. J. Pharmacol. 37, 57 (1969)CrossRefGoogle Scholar
  7. 7.
    Chalmers, J.P., Baldessarini, R.J., Wurtman, R.J.: Effects of L-dopa on norepinephrine metabolism in the brain. Proc. nat. Acad. Sei. (Wash) 68, 662 (1971)Google Scholar
  8. 8.
    Ferrini, R., Glässer, A.: In vitro decarboxylation of new phenylalanine derivatives. Biochem. Pharmacol. 13, 798 (1964)PubMedCrossRefGoogle Scholar
  9. 9.
    Finkelstein, J.D., Kyle, W.E., Harris, B.J.: Methionine metabolism in mammals. Regulation of homocysteine methyltransferase in rat tissue. Arch. Biochem. 146, 84(1971)PubMedCrossRefGoogle Scholar
  10. 10.
    Langer, B.W.: Organ and intracellular location of the methionine methyl group synthesizing system of the rat. Proc. Soc. exp. Biol. (Ny.) 115, 1088 (1964)CrossRefGoogle Scholar
  11. 11.
    Levitt, M., Nixon, P.F., Pincus, J.H., Bertino, J.R.: Transport characteristics of folates in cerebrospinal fluid; a study utilizing doubly labeled 5-methyltetrahydro-folate and 5-formyltetrahydrofolate. J. clin. Invest. 50, 1301 (1971)PubMedCrossRefGoogle Scholar
  12. 12.
    Lytle, L.D., Hurko, O., Romero, J.A., Cottman, K., Leehey, D., Wurtman, R.J.: The effects of 6-hydroxydopamine pretreatment on the accumulation of dopa and dopamine in brain and peripheral organs following L-dopa administration. J. Neural Transm. 33, 63 (1972)PubMedCrossRefGoogle Scholar
  13. 13.
    Ordonez, L.A., Wurtman, R.J.: Methylation of exogenous 3, 4-dihydroxyphenylalanine: Effects on methyl group metabolism. Biochem. Pharmacol. 22, 134 (1973a)PubMedCrossRefGoogle Scholar
  14. 14.
    Ordonez, L.A., Wurtman, R.J.: Enzymes catalyzing the de novo synthesis of methyl groups in the brain and other tissues of the rat. J. Neurochem. 21, 1447 (1973b)PubMedCrossRefGoogle Scholar
  15. 15.
    Ordonez, L.A., Wurtman, R.J.: Folic acid deficiency and methyl group metabolism in rat brain: Effects of L-dopa. Arch. Biochem. 160, 372 (1974)PubMedCrossRefGoogle Scholar
  16. 16.
    Ordonez, L.A., Ambrus, M., Boyson, S., Goodman, M.N., Ruderman, N.B., Wurtman, R.J.: Skeletal muscle: Reservoir for exogenously administered L-dopa. J. Pharmacol., exp. Ther. 190, 187 (1974)Google Scholar
  17. 17.
    Pan, F., Tarver, H.: Comparative studies on methionine, selenomethionine, and their ethyl analogues as substrates for methionine adenosyltransferase from rat liver. Arch. Biochem. 119, 429 (1967)PubMedCrossRefGoogle Scholar
  18. 18.
    Romero, J.A., Chalmers, J.P., Cottman, K., Lytle, L.D., Wurtman, R.J.: Regional effects of L-dihydroxyphenylalanine (L-dopa) on norepinephrine metabolism in rat brain. J. Pharmacol, exp. Ther. 180, 277 (1972)Google Scholar
  19. 19.
    Romero, J.A., Lytle, L.D., Ordonez, L.A., Wurtman, R.J.: Effects of L-dopa administration on the concentrations of dopa, dopamine, and norepinephrine in various rat tissues. J. Pharmacol, exp. Ther. 184, 67 (1973)Google Scholar
  20. 20.
    Rubin, R.A., Ordonez, L.A., Wurtman, R.J.: Physiological dependence of brain methionine and SAMe concentrations on the serum amino acid pattern. J. Neurochem. 23, 227(1974)PubMedCrossRefGoogle Scholar
  21. 21.
    Wurtman, R.J.: Catecholamines. Boston: Little, Brown and Co., 1966Google Scholar
  22. 22.
    Wurtman, R.J., Chou, C, Rose, C: The fate of Cl4-dihydroxyphenylalanine in the whole mouse. J. Pharmacol, exp. Ther. 174, 351 (1970a)Google Scholar
  23. 23.
    Wurtman, R.J.: Rose, CM., Matthysse, S., Stephenson, J., Baldessarini R.J.: L-dihydroxyphenylalanine: Effect on S-adenosylmethionine in brain. Science 169, 395 (1970b)PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1978

Authors and Affiliations

  • R. J. Wurtman
    • 1
  • L. A. Ordonez
    • 2
  1. 1.Laboratory of Neuroendocrine Regulation, Department of Nutrition and Food ScienceMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Catedra de Fisiopatologia, Instituto de Medicina ExperimentalUniversidad Central de VenezuelaCaracasVenezuela

Personalised recommendations