Biochemical mechanisms leading to tryptophan 2,3-dioxygenase activation
Autor(es): Li, Junsuo S.; Han, Qian; Fang, Jianmin; Rizzi, Menico; James, Anthony A.; Li, Jianyong
Resumo: Tryptophan 2,3-dioxygenose (TDO) is the first enzyme in the tryptophon oxidation pathway. It is a hemoprotein and its heme prosthetic group is present as a heme-ferric (heme-Fe3+) form that is not active. To be able to oxidize tryptophon, the heme-Fe3+ 31 form of the enzyme must be reduced to a heme-ferrous (heme-Fe2+) form and this study describes conditions that promote TDO activation. TDO is progressively activated upon mixing with tryptophan in a neutral buffer, which leads to on impression that tryptophon is responsible for TDO activation. Through extensive analysis of factors resulting in TDO activation during incubation with tryptophan, we conclude that tryptophan indirectly activates TDO through promoting the production of reactive oxygen species. This consideration is supported by the virtual elimination of the initial lag phase when either preincubated tryptophan solution was used as the substrate or a low concentration of superoxide of hydrogen peroxide was incorporated into the freshly tryptophon and TDO mixture. However, accumulation of these reactive oxygen species also leads to the inactivation of TDO, so that both TDO activation and inactivation proceed with the specific outcome depending greatly on the concentrations of superoxide and hydrogen peroxide. As a consequence, the rate of TDO catalysis varies depending upon the proportion of the active to inactive forms of the enzyme, which is in a dynamic relationship in the reaction mixture. These data provide some insight towards elucidating the molecular regulation of TDO in vivo.
Palavras-Chave: Tryptophan 2,3-dioxygenase; Aedes aegypti; Superoxide; Hydrogen peroxide; Ascorbate
Imprenta: Archives of Insect Biochemistry and Physiology, v. 64, n. 2, p. 74-87, 2007
Identificador do objeto digital: 10.1002/arch.20159
Descritores: Aedes aegypti - Cell
Data de publicação: 2007
