Analysis of Reaction Intermediates in Tryptophan 2,3-Dioxygenase: A Comparison with Indoleamine 2,3-Dioxygenase

• DOI: 10.1021/acs.biochem.6b01005
• Publication Date: 2016-12-01T12:07:24Z
• Authors: Jaswir Basran; Elizabeth S. Booth; Michael Lee; Sandeep Handa; Emma L. Raven
• Keywords: Indoleamine 2,3-dioxygenase; Dioxygenase; Tryptophan Metabolism

Indoleamine 2,3-dioxygenase (IDO) and tryptophan (TDO) are heme-containing enzymes that catalyze the O2-dependent oxidation of l-tryptophan (l-Trp) in biological systems. Although many decades have passed since their discovery, mechanism has not been established. It widely assumed IDO TDO react using same mechanism, although there is no evidence they do. For IDO, a Compound II (ferryl) species accumulates steady state implicated mechanism; TDO, such ever observed. In this paper, we examine kinetics TDO. We find for accumulation during catalysis. Instead, ternary [Fe(II)–O2, l-Trp] complex detected under conditions. The absence due to an intrinsic inability enzyme form ferryl heme, because can be formed directly through different route which ferrous heme reacted with peroxide. interpret data mean rate-limiting step mechanisms same.