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Synthesis and Quantitative Aspects of Dihydrobiopterin Control of Cerebral Serotonin Levels

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Serotonin

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 133))

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Abstract

Soon after the isolation of 7,8-dihydrobiopterin from rat liver,1 the structure of the naturally occurring cofactor of hydroxylases 5,6,7,8-tetrahydrobiopterin (BH4) was established. Unequivocal proof of the biosynthesis of its precursors quinonoid-D-erythrodihydroneopterin triphosphate and quinonoid-L-erythrodihydrobiopterin from GTP was documented in a series of reports.2,3,4,5 Significant to the understanding of the formation of BH4 was the characterization of an enzyme, quinonoid dihydrobiopterin reductase (DHPR) (EC1.6.99.7) which catalyzes the reduction of quinonoid-L- erythrodihydrobiopterin (q-BH2) in presence of NADH2 or NADPH2.6,7 The coupled oxido-reductive reaction q-BH2+2H++2e−⇌BH4+O2+substrate → product +H2O enables the fast shuttle of 2H++2e−.

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References

  1. S. Kaufman, The structure of phenylalanine hydroxylase cofactor, Proc. Nat. Acad. Sci. U.S.A. 50:1085–1092 (1963).

    Article  CAS  Google Scholar 

  2. E. M. Gâl and A. D. Sherman, Biopterin II: Evidence for cerebral synthesis of 7,8-dihydrobiopterin in vivo and in vitro, Neurochem. Res. 1:627–639 (1976).

    Article  Google Scholar 

  3. E. M. Gâl, J. M. Nelson, and A. D. Sherman, Biopterin III: Purification and characterization of enzymes involved in the cerebral synthesis of 7,8-dihydrobiopterin, Neurochem. Res. 3:69–88 (1978).

    Article  PubMed  Google Scholar 

  4. E. M. Gâl, F. A. Henn, and A. Sherman, Biopterin IV: Regional and subcellular aspects of L-erythro-7,8-dihydrobiopterin synthesis in brain, Neurochem. Res. 3:493–499 (1978).

    Article  PubMed  Google Scholar 

  5. E. M. Gâl and A. D. Sherman, 6-(D-erythro-1’,2’,3’-trihydroxypropyl)-7,8-dihydropterin triphosphate synthetase, Fed. Proc. 38:324 (1979).

    Google Scholar 

  6. J. E. Crame, E. S. Hall, and S. Kaufman, The isolation and characterization of dihydropteridine reductase from sheep liver, J.Biol. Chem. 247:6082–6091 (1972).

    Google Scholar 

  7. H. Snady and J. M. Musacchio, Quinonoid dihydropterin reductaseII regional and subcellular distribution of rat brain enzyme, Biochem Pharmacol. 27:1947–1953 (1978).

    Article  PubMed  CAS  Google Scholar 

  8. E. M. Gail, Biosynthesis and function of unconjugated pterins in the mammalian tissues, In “Advances in Neurochemistry vol. 4,” B.W. Agranoff and M. H. Aprison, eds., Plenum Publishing, New York (in press).

    Google Scholar 

  9. E. M. Gâl, G. Hanson, and A. D. Sherman, Biopterin I: Profile and quantitation in rat brain, Neurochem. Res. 1:511–523 (1976).

    Article  Google Scholar 

  10. R. A. Levine, D. M. Kuhn, and W. Lovenberg, The regional distribution of hydroxylase cofactor in rat brain, J. Neurochem. 32:1575–1578 (1979).

    Article  PubMed  CAS  Google Scholar 

  11. E. M. Gál and A. D. Sherman, Rapid isolation and quantitation of biopterin, neopterin, and their guanine ribotide precursor from biological samples, Prep. Biochem. 7(2):155–164 (1978).

    Google Scholar 

  12. H.-Ch. Curtius, A. Niederwieser, M. Viscontini, A. Otten, J. Schaub, S. Scheibenreiter, and H. Schmidt, Atypical phenylketonuria due to tetrahydrobiopterin deficiency. Diagnosis and treatment with tetrahydrobiopterin, dihydrobiopterin and sepiapterin, Clin. Chini. Acta. 93:251–262 (1979).

    Article  CAS  Google Scholar 

  13. E. M. Gel and A. D. Sherman, Phosphorylation, a factor controlling the synthesis of L-erythrodihydrobiopterin (BH2), Biochem, Biophys. Res. Com. 83:593–598 (1978).

    Article  Google Scholar 

  14. E. M. Gel, M. R. Dawson, D. T. Dudley, and A. D. Sherman, Biopterin VI: Purification and primary amino acid sequence of mammalian D-erythro-7,8-dihydroneopterin triphosphate synthetase, Neurochem. Res. 4:605–626 (1979).

    Article  Google Scholar 

  15. K. Fukushima, W. E. Richter, Jr., and T. Shiota, Partial purification of 6-(D-erythro-1’,2’,3’-trihydroxypropyl)-7, 8-dihydropterin triphosphate synthetase from chicken liver, J. Biol. Chem. 252:5750–5755 (1977).

    PubMed  CAS  Google Scholar 

  16. E. M. Ggl, J. A. Bybee, and A. D. Sherman, Biopterin V: De novo synthesis of dihydrobiopterin: evidence for its quinonoid structure and lack of dependence of its reduction to tetrahydrobiopterin on dihydrofolate reductase, J. Neurochem. 32:179–186 (1979).

    Article  Google Scholar 

  17. W. P. Bullard, P. B. Guthrie, V. Russo, and A. J. Mandell, Regional and subcellular distribution and some factors in the regulation of reduced pterins in rat brain, J. Pharmacol. Exp. Ther. 206:4–20 (1978).

    PubMed  CAS  Google Scholar 

  18. A. D. Sherman and E. M. Ggl, Lack of dependence of amine or prostaglandin biosynthesis on absolute cerebral level of pteridine cofactor, Life Sciences. 23:1675–1680 (1978).

    Article  PubMed  CAS  Google Scholar 

  19. E. M. Gel and A. D. Sherman, Synthesis and metabolism of L-kynurenine in rat brain, J. Neurochem. 30:607–613 (1978).

    Article  Google Scholar 

  20. R. Kettler, G. Bartholini, and A. Pletscher, In vivo enhancement of tyrosine hydroxylation in rat striatum by tetrahydrobiopterin, Nature. 249:476–478 (1974).

    Article  PubMed  CAS  Google Scholar 

  21. E. M. Gel, Tryptophan-5-hydroxylase: function and control, In: “Advances in Biochem. Psychopharmacol., Vol. 11,” E. Costa, G. L. Gessa, and M. Sandler, eds., Raven Press, New York, pp. 1–10 (1974).

    Google Scholar 

  22. S. W. Bailey and J. E. Ayling, Separation and properties of the 6-diastereoisomers of L-erythrotetrahydrobiopterin and their reactivities with phenylalanine hydroxylase, J. Biol. Chem. 253:1598–1605 (1978).

    PubMed  CAS  Google Scholar 

  23. T. Nagatsu, K. Mizutani, I. Nagatsu, S. Matsuura, and T. Sugimoto, Pteridines as cofactor of inhibitor of tyrosine hydroxylase, Biochem. Pharmacol. 21:1945–1953 (1972).

    Article  PubMed  CAS  Google Scholar 

  24. T. Lloyd and J. Weisz, Direct inhibition of tyrosine hydroxylase activity by catechol estrogens, J. Biol. Chem. 253:4841–4843 (1978).

    PubMed  CAS  Google Scholar 

  25. S. P. Mann and J. I. Gordon, Inhibition of guinea-pig brain tyrosine hydroxylase by catechols and biopterin, J. Neurochem. 33:133–138 (1979).

    Article  PubMed  CAS  Google Scholar 

  26. B. Jarrott, The cellular localization and physiological role of catechol-O-methyl transferase in the body, In: “Frontiers in Cathecholamine Research,” E. Usdin and S. Snyder, eds., Pergamon Press, New York, pp. 133–138 (1973).

    Google Scholar 

  27. B. Zivkovic, A. Guidotti, and E. Costa, Effects of Neuroleptics on striatal tyrosine hydroxylase: Changes in affinity for the pteridine cofactor, Molec. Pharmacol. 10:727–735 (1975).

    Google Scholar 

  28. M. Hamon, S. Bourgoin, F. Artaud, and F. Hery, Rat brain stem tryptophan hydroxylase: mechanism of activation by calcium, J. Neurochem. 28:811–818 (1977).

    Article  PubMed  CAS  Google Scholar 

  29. R. H. Roth and P. M. Salzman, Role of calcium in the depolarization-induced activation of tyrosine hydroxylase, In: “Structure and Function of Monoamine Enzymes,” E. Usdin, N. Weiner, and M. B. H. Youdim, eds., Dekker, New York, pp. 149–168 (1977).

    Google Scholar 

  30. S. Kaufman, Metabolism of the phenylalanine hydroxylation cofactor, J. Biol. Chem. 242:3934–3943 (1967).

    PubMed  CAS  Google Scholar 

  31. E. M. Gal, M. Poczik, and F. D. Marshall, Hydroxylation of tryptophan to 5-hydroxytryptophan by brain tissue in vivo, Biochem. and Biophys. Res. Com. 12:39–43 (1963).

    Article  CAS  Google Scholar 

  32. D. G. Grahame-Smith, Tryptophan hydroxylation in brain, Biochem. and Biophys. Res. Com. 16:586–592 (1964).

    Article  CAS  Google Scholar 

  33. E. M. Gal, J. C. Armstrong, and B. Ginsberg, The nature of in vitro hydroxylation of L-tryptophan by brain tissue. J. Neurochem. 13:643–654 (1966).

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Neurochemical Research Laboratories Department of Psychiatry, College of Medicine University of Iowa, Iowa City, Iowa, 52242, USA

    E. Martin Gál

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  1. E. Martin Gál
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Editors and Affiliations

  1. The University of Texas Medical Branch, Galveston, Texas, USA

    Bernard Haber

  2. Veterans Administration Medical Center, Brockton, Massachusetts, USA

    Sabit Gabay

  3. Brown University Division of Psychiatry and Human Behavior, Providence, Rhode Island, USA

    Sabit Gabay

  4. University of Athens School of Medicine, Athens, Greece

    M. R. Issidorides  & S. G. A. Alivisatos  & 

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© 1981 Plenum Press, New York

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Gál, E.M. (1981). Synthesis and Quantitative Aspects of Dihydrobiopterin Control of Cerebral Serotonin Levels. In: Haber, B., Gabay, S., Issidorides, M.R., Alivisatos, S.G.A. (eds) Serotonin. Advances in Experimental Medicine and Biology, vol 133. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-3860-4_10

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  • DOI: https://doi.org/10.1007/978-1-4684-3860-4_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-3862-8

  • Online ISBN: 978-1-4684-3860-4

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