Mechanism of Oxygen Activation by Tyrosine Hydroxylase

Thomas A. Dix, Stephen Benkovic, Donald M. Kuhn

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The mechanism by which the tetrahydropterin-requiring enzyme tyrosine hydroxylase (TH) activates dioxygen for substrate hydroxylation was explored. TH contains one ferrous iron per subunit and catalyzes the conversion of its tetrahydropterin cofactor to a 4a-carbinolamine concomitant with substrate hydroxylation. These results are in accord with shared mechanisms of oxygen activation by TH and the more commonly studied tetrahydropterin-dependent enzyme phenylalanine hydroxylase (PAH) and strongly suggest that a peroxytetrahydropterin is the hydroxylating species generated during TH turnover. In addition, TH can also utilize H202 as a cofactor for substrate hydroxylation, a result not previously established for PAH. A detailed mechanism for the reaction is proposed. While the overall pattern of tetrahydropterin-dependent oxygen activation by TH and PAH is similar, the H202-dependent hydroxylation performed by TH provides an indication that subtle differences in the Fe ligand field exist between the two enzymes. The mechanistic ramifications of these results are briefly discussed.

Original languageEnglish (US)
Pages (from-to)3354-3361
Number of pages8
JournalBiochemistry
Volume26
Issue number12
DOIs
StatePublished - Jan 1 1987

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Tyrosine 3-Monooxygenase
Chemical activation
Hydroxylation
Oxygen
Phenylalanine Hydroxylase
Substrates
Enzymes
Iron
Ligands
tetrahydropterin

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Dix, T. A., Benkovic, S., & Kuhn, D. M. (1987). Mechanism of Oxygen Activation by Tyrosine Hydroxylase. Biochemistry, 26(12), 3354-3361. https://doi.org/10.1021/bi00386a016
Dix, Thomas A. ; Benkovic, Stephen ; Kuhn, Donald M. / Mechanism of Oxygen Activation by Tyrosine Hydroxylase. In: Biochemistry. 1987 ; Vol. 26, No. 12. pp. 3354-3361.
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Dix, TA, Benkovic, S & Kuhn, DM 1987, 'Mechanism of Oxygen Activation by Tyrosine Hydroxylase', Biochemistry, vol. 26, no. 12, pp. 3354-3361. https://doi.org/10.1021/bi00386a016

Mechanism of Oxygen Activation by Tyrosine Hydroxylase. / Dix, Thomas A.; Benkovic, Stephen; Kuhn, Donald M.

In: Biochemistry, Vol. 26, No. 12, 01.01.1987, p. 3354-3361.

Research output: Contribution to journalArticle

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