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Amino Acids

, Volume 34, Issue 3, pp 455–464 | Cite as

Oxygen dependence of tyrosine hydroxylase

  • M. Rostrup
  • A. Fossbakk
  • A. Hauge
  • R. Kleppe
  • E. Gnaiger
  • J. Haavik
Article

Summary.

The effects of dioxygen on tyrosine hydroxylase (TH) activity was studied, measuring the formation of DOPA from tyrosine, 3H2O from 3,5-3H-tyrosine, or by direct oxygraphic determination of oxygen consumption. A high enzyme activity was observed during the initial 1–2 min of the reactions, followed by a decline in activity, possibly related to a turnover dependent substoichiometrical oxidation of enzyme bound Fe(II) to the inactive Fe(III) state. During the initial reaction phase, apparent K m-values of 29–45 µM for dioxygen were determined for all human TH isoforms, i.e. 2–40 times higher than previously reported for TH isolated from animal tissues. After 8 min incubation, the K m (O2)-values had declined to an average of 20 ± 4 µM. Thus, TH activity may be severely limited by oxygen availability even at moderate hypoxic conditions, and the enzyme is rapidly and turnover dependent inactivated at the experimental conditions commonly employed to measure in vitro activities.

Keywords: Catecholamines – Human – Hypoxia – Oxygen – Tyrosine hydroxylase 

Abbreviations:

BH4

(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin

4aOH-BH4

4a-hydroxytetrahydrobiopterin

q-BH2

quinonoid dihydrobiopterin

DTT

dithiothreitol

hTH

human tyrosine hydroxylase

PAH

phenylalanine hydroxylase

TH

tyrosine hydroxylase

Enzymes: phenylalanine hydroxylase

EC 1.14.16.1

tyrosine hydroxylase

EC 1.14.16.2

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References

  1. Almas, B, Le Bourdelles, B, Flatmark, T, Mallet, J, Haavik, J 1992Regulation of recombinant human tyrosine hydroxylase isozymes by catecholamine binding and phosphorylation. Structure/activity studies and mechanistic implicationsEur J Biochem209249255PubMedCrossRefGoogle Scholar
  2. Andersson, KK, Vassort, C, Brennan, BA, Que, L,Jr, Haavik, J, Flatmark, T, Gros, F, Thibault, J 1992Purification and characterization of the blue-green rat phaeochromocytoma (PC12) tyrosine hydroxylase with a dopamine-Fe(III) complex. Reversal of the endogenous feedback inhibition by phosphorylation of serine-40Biochem J284687695PubMedGoogle Scholar
  3. Bisgard, GE 1995Increase in carotid body sensitivity during sustained hypoxiaBiol Signals4292297PubMedCrossRefGoogle Scholar
  4. Brown, RM, Kehr, W, Carlsson, A 1975Functional and biochemical aspects of catecholamine metabolism in brain under hypoxiaBrain Res85491509PubMedCrossRefGoogle Scholar
  5. Czyzyk-Krzeska, MF, Furnari, BA, Lawson, EE, Millhorn, DE 1994Hypoxia increases rate of transcription and stability of tyrosine hydroxylase mRNA in pheochromocytoma (PC12) cellsJ Biol Chem269760764PubMedGoogle Scholar
  6. Davis, JN 1976Brain tyrosine hydroxylation: alteration of oxygen affinity in vivo by immobilization or electroshock in the ratJ Neurochem27211215PubMedCrossRefGoogle Scholar
  7. Davis, JN, Carlsson, A 1973Effect of hypoxia on tyrosine and tryptophan hydroxylation in unanaesthetized rat brainJ Neurochem20913915PubMedCrossRefGoogle Scholar
  8. Feinsilver, SH, Wong, R, Raybin, DM 1987Adaptations of neurotransmitter synthesis to chronic hypoxia in cell cultureBiochim Biophys Acta9285662PubMedCrossRefGoogle Scholar
  9. Fisher, DB, Kaufman, S 1972The inhibition of phenylalanine and tyrosine hydroxylases by high oxygen levelsJ Neurochem1913591365PubMedCrossRefGoogle Scholar
  10. Fitzpatrick, PF 1991Steady-state kinetic mechanism of rat tyrosine hydroxylaseBiochemistry3036583662PubMedCrossRefGoogle Scholar
  11. Fitzpatrick, PF 2003Mechanism of aromatic amino acid hydroxylationBiochemistry421408314091PubMedCrossRefGoogle Scholar
  12. Fitzpatrick, PF, Chlumsky, LJ, Daubner, SC, O’Malley, KL 1990Expression of rat tyrosine hydroxylase in insect tissue culture cells and purification and characterization of the cloned enzymeJ Biol Chem26520422047PubMedGoogle Scholar
  13. Flatmark, T, Almas, B, Knappskog, PM, Berge, SV, Svebak, RM, Chehin, R, Muga, A, Martinez, A 1999Tyrosine hydroxylase binds tetrahydrobiopterin cofactor with negative cooperativity, as shown by kinetic analyses and surface plasmon resonance detectionEur J Biochem262840849PubMedCrossRefGoogle Scholar
  14. Fossbakk, A, Haavik, J 2005An oxygraphic method for determining kinetic properties and catalytic mechanism of aromatic amino acid hydroxylasesAnal Biochem343100105PubMedCrossRefGoogle Scholar
  15. Frantom, PA, Seravalli, J, Ragsdale, SW, Fitzpatrick, PF 2006Reduction and oxidation of the active site iron in tyrosine hydroxylase: kinetics and specificityBiochemistry454338CrossRefGoogle Scholar
  16. Gnaiger, E, Steinlechner-Maran, R, Mendez, G, Eberl, T, Margreiter, R 1995Control of mitochondrial and cellular respiration by oxygenJ Bioenerg Biomembr27583596PubMedCrossRefGoogle Scholar
  17. Goodwill, KE, Sabatier, C, Marks, C, Raag, R, Fitzpatrick, PF, Stevens, RC 1997Crystal structure of tyrosine hydroxylase at 2.3 A and its implications for inherited neurodegenerative diseasesNat Struct Biol4578585PubMedCrossRefGoogle Scholar
  18. Gozal, E, Shah, ZA, Pequignot, JM, Pequignot, J, Sachleben, LR, Czyzyk-Krzeska, MF, Li, RC, Guo, SZ, Gozal, D 2005Tyrosine hydroxylase expression and activity in the rat brain: differential regulation after long-term intermittent or sustained hypoxiaJ Appl Physiol99642649PubMedCrossRefGoogle Scholar
  19. Grima, B, Lamouroux, A, Boni, C, Julien, JF, Javoy-Agid, F, Mallet, J 1987A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristicsNature326707711PubMedCrossRefGoogle Scholar
  20. Haavik, J, Andersson, KK, Petersson, L, Flatmark, T 1988Soluble tyrosine hydroxylase (tyrosine 3-monooxygenase) from bovine adrenal medulla: large-scale purification and physicochemical propertiesBiochim Biophys Acta953142156PubMedGoogle Scholar
  21. Haavik, J, Flatmark, T 1980Rapid and sensitive assay of tyrosine 3-monooxygenase activity by high-performance liquid chromatography using the native fluorescence of DOPAJ Chromatogr198511515PubMedCrossRefGoogle Scholar
  22. Haavik, J, Flatmark, T 1983Isolation and characterization of quinonoid dihydropterins by high-performance liquid chromatographyJ Chromatogr257361372CrossRefGoogle Scholar
  23. Haavik, J, Flatmark, T 1987Isolation and characterization of tetrahydropterin oxidation products generated in the tyrosine 3-monooxygenase (tyrosine hydroxylase) reactionEur J Biochem1682126PubMedCrossRefGoogle Scholar
  24. Haavik, J, Le Bourdelles, B, Martinez, A, Flatmark, T, Mallet, J 1991Recombinant human tyrosine hydroxylase isozymes. Reconstitution with iron and inhibitory effect of other metal ionsEur J Biochem199371378PubMedCrossRefGoogle Scholar
  25. Haavik, J, Martinez, A, Olafsdottir, S, Mallet, J, Flatmark, T 1992The incorporation of divalent metal ions into recombinant human tyrosine hydroxylase apoenzymes studied by intrinsic fluorescence and 1H-NMR spectroscopyEur J Biochem2102331PubMedCrossRefGoogle Scholar
  26. Hayashi, Y, Miwa, S, Lee, K, Koshimura, K, Hamahata, K, Hasegawa, H, Fujiwara, M, Watanabe, Y 1990Enhancement of in vivo tyrosine hydroxylation in the rat adrenal gland under hypoxic conditionsJ Neurochem5411151121PubMedCrossRefGoogle Scholar
  27. Hirsila, M, Koivunen, P, Gunzler, V, Kivirikko, KI, Myllyharju, J 2003Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factorJ Biol Chem2783077230780PubMedCrossRefGoogle Scholar
  28. Ikeda, M, Fahien, LA, Udenfriend, S 1966A kinetic study of bovine adrenal tyrosine hydroxylaseJ Biol Chem24144524456PubMedGoogle Scholar
  29. Katz, IR 1980Oxygen affinity of tyrosine and tryptophan hydroxylases in synaptosomesJ Neurochem35760763PubMedCrossRefGoogle Scholar
  30. Knappskog, M, Eiken, HG, Martinez, A, Olafsdottir, S, Haavik, J, Flatmark, T, Apold, J 1993Expression of wild type and mutant forms of human phenylalanine hydroxylase in E. coli Adv Exp Med Biol3385962PubMedGoogle Scholar
  31. Koch, R 1996Tyrosine supplementation for phenylketonuria treatmentAm J Clin Nutr64974975PubMedGoogle Scholar
  32. Kuhn, DM, Aretha, CW, Geddes, TJ 1999Peroxynitrite inactivation of tyrosine hydroxylase: mediation by sulfhydryl oxidation, not tyrosine nitrationJ Neurosci191028910294PubMedGoogle Scholar
  33. Leuenberger, U, Gleeson, K, Wroblewski, K, Prophet, S, Zelis, R, Zwillich, C, Sinoway, L 1991Norepinephrine clearance is increased during acute hypoxemia in humansAm J Physiol261H1659H1664PubMedGoogle Scholar
  34. Meyer-Klaucke, W, Winkler, H, Schunemann, V, Trautwein, AX, Nolting, HF, Haavik, J 1996Mossbauer, electron-paramagnetic-resonance and X-ray-absorption fine-structure studies of the iron environment in recombinant human tyrosine hydroxylaseEur J Biochem241432439PubMedCrossRefGoogle Scholar
  35. Numata, Y, Kato, T, Nagatsu, T, Sugimoto, T, Matsuura, S 1977Effects of stereochemical structures of tetrahydrobiopterin on tyrosine hydroxylaseBiochim Biophys Acta480104112PubMedGoogle Scholar
  36. Ramsey, AJ, Hillas, PJ, Fitzpatrick, PF 1996Characterization of the active site iron in tyrosine hydroxylase. Redox states of the ironJ Biol Chem2712439524400PubMedCrossRefGoogle Scholar
  37. Rolett, EL, Azzawi, A, Liu, KJ, Yongbi, MN, Swartz, HM, Dunn, JF 2000Critical oxygen tension in rat brain: a combined (31)P-NMR and EPR oximetry studyAm J Physiol Regul Integr Comp Physiol279R9R16PubMedGoogle Scholar
  38. Rostrup, M 1998Catecholamines, hypoxia and high altitudeActa Physiol Scand162389399PubMedCrossRefGoogle Scholar
  39. Sevre, K, Bendz, B, Hanko, E, Nakstad, AR, Hauge, A, Kasin, JI, Lefrandt, JD, Smit, AJ, Eide, I, Rostrup, M 2001Reduced autonomic activity during stepwise exposure to high altitudeActa Physiol Scand173409417PubMedCrossRefGoogle Scholar
  40. Siggaard-Andersen, O, Fogh-Andersen, N, Gothgen, IH, Larsen, VH 1995Oxygen status of arterial and mixed venous bloodCrit Care Med2312841293PubMedCrossRefGoogle Scholar
  41. Smith, RH, Guilbeau, EJ, Reneau, DD 1977The oxygen tension field within a discrete volume of cerebral cortexMicrovasc Res13233240PubMedCrossRefGoogle Scholar
  42. Thony, B, Blau, N 2006Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductaseHum Mutat27870878PubMedCrossRefGoogle Scholar
  43. Wallick, DE, Bloom, LM, Gaffney, BJ, Benkovic, SJ 1984Reductive activation of phenylalanine hydroxylase and its effect on the redox state of the non-heme ironBiochemistry2312951302PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • M. Rostrup
    • 1
  • A. Fossbakk
    • 2
  • A. Hauge
    • 3
  • R. Kleppe
    • 2
  • E. Gnaiger
    • 4
  • J. Haavik
    • 2
  1. 1.Cardiovascular and Renal Research Centre, Department of Acute MedicineUllevaal University HospitalOsloNorway
  2. 2.Department of Biomedicine, Haukeland University HospitalUniversity of BergenBergenNorway
  3. 3.School of Medicine, The Institute of PhysiologyUniversity of OsloOsloNorway
  4. 4.D. Swarovski Research Laboratory, Department of Transplant SurgeryUniversity Hospital InnsbruckInnsbruckAustria

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