On the catalytic mechanism of tryptophan hydroxylase

Graham R. Moran, Agnes Derecskei-Kovacs, Patrick J. Hillas, Paul F. Fitzpatrick

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Tryptophan hydroxylase catalyzes the hydroxylation of tryptophan using tetrahydrobiopterin and molecular oxygen. With tyrosine as a substrate, the amount of C4a-hydroxypterin formed greatly exceeds the amount of dihydroxyphenylalanine formed, consistent with oxygen-oxygen bond cleavage occurring in a step prior to amino acid hydroxylation. With L-indole-2H5- tryptophan, L-4-2H- or L-5-2H-tryptophan as substrate there is no isotope effect on the V/K value for tryptophan. There is an inverse isotope effect on the V(max) value with L-indole-2H5-tryptophan and L-5-2H-tryptophan, but no effect with L-4-2H-tryptophan. Comparison of the measured isotope effects with values of calculated secondary equilibrium isotope effects for tryptophan hydroxylation indicate that the results are most consistent with the formation of a cationic species. Retention of the isotopic label from L- 5-2H-tryptophan in the product confirms that an NIH shift occurs in tryptophan hydroxylase and shows that the direction of shift is from carbon 5 to carbon 4. The degree of retention of the deuterium is higher when the deuterium is initially on carbon 4 rather than carbon 5.

Original languageEnglish (US)
Pages (from-to)4535-4541
Number of pages7
JournalJournal of the American Chemical Society
Issue number19
StatePublished - May 17 2000

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry


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