ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P161. Oxidation of L-Tryptophan in Biology
E. Raven a , J. Basran b , S. Rafice a , N. Chauhan a , I. Efimov a , M. Cheesman c
a Chemistry, University of Leicester, University Road, LE1 7RH, Leicester, United Kingdom,
b Biochemistry, University of Leicester, Lancaster Road, le1 9hn, Leicester, United Kingdom
c Chemical Sciences and Pharmacy, University of East Anglia, Earlham Road, NR4 7TJ, Norwich, United
Kingdom
e-mail: emma.raven@le.ac.uk
The L-kynurenine pathway – which leads to the formation of NAD – is the major catabolic route of L-tryptophan
metabolism in biology. The initial step in this pathway is oxidation of L-tryptophan to N-formylkynurenine,
Scheme 1. In all biological systems examined to date, this is catalysed by one of two heme enzymes, tryptophan
2, 3-dioxygenase (TDO) or indoleamine 2, 3 dioxygenase (IDO), in a reaction mechanism that involves binding
of dioxygen to ferrous heme. Although they catalyse the same reaction, TDO and IDO are otherwise distinct and
we know little about their structure and mechanism.
There is essentially nothing known about human TDO. Here, we describe spectroscopic, kinetic and redox
analyses on recombinant human TDO [1]. We find unexpected differences between human TDO and the closely
related human IDO [2] in terms of both substrate binding and the catalytic reaction intermediates. These data
widen the scope of information available on these new heme dioxygenase enzymes and we use it to make
functional comparisons both with human IDO and more generally across the heme dioxygenase family.
References:
[1] Basran, J.; Rafice, S.; Chauhan, N.; Efimov, I.; Cheesman, M. R.; Ghamsari, L.; Raven, E. L. Biochemistry
2008, 47, 4752-4760.
[2] Chauhan, N.; Basran, J.; Efimov, I.; Svistunenko, D. A.; Seward, H. E.; Peter C. E. Moody, Raven, E. L.
Biochemistry 2008, 47, 4761-4769.
_____________________________________________________________________
280