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Oxygen dependence of tyrosine hydroxylase

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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.

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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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Authors and Affiliations

  1. Cardiovascular and Renal Research Centre, Department of Acute Medicine, Ullevaal University Hospital, Oslo, Norway

    M. Rostrup

  2. Department of Biomedicine, Haukeland University Hospital, University of Bergen, Bergen, Norway

    A. Fossbakk, R. Kleppe & J. Haavik

  3. School of Medicine, The Institute of Physiology, University of Oslo, Oslo, Norway

    A. Hauge

  4. D. Swarovski Research Laboratory, Department of Transplant Surgery, University Hospital Innsbruck, Innsbruck, Austria

    E. Gnaiger

Authors
  1. M. Rostrup
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  2. A. Fossbakk
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  3. A. Hauge
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  4. R. Kleppe
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  5. E. Gnaiger
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  6. J. Haavik
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Authors’ address: Jan Haavik, Department of Biomedicine, University of Bergen, 5009 Bergen, Norway

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Rostrup, M., Fossbakk, A., Hauge, A. et al. Oxygen dependence of tyrosine hydroxylase. Amino Acids 34, 455–464 (2008). https://doi.org/10.1007/s00726-007-0547-7

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  • DOI: https://doi.org/10.1007/s00726-007-0547-7

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