Thyroidal iodotyrosine deiodinase (IYD) is the only known mammalian enzyme that depends on bound flavin mononucleotide (FMN) to catalyze reductive dehalogenation. The ability of FMN to promote one- and two-electron reductions in combination with the ability of the C-I bond to undergo both homolytic and heterolytic cleavage raises possibilities of both radical and polar mechanisms for IYD. Human IYD has been expressed heterologously and characterized with the steady-state and rapid kinetics. Enzyme promotes deiodination, debromination, dechlorination but not defluorination of the respective ortho-halogenated tyrosines. Substrate binding was determined to be faster than dehalogenation based on the measured second order oxidation rate constants and the binding rate constants. Dehalogenation, thus, might be a rate-limiting step. A transient absorbance connected with a neutral blue semiquinone radical was observed during dechlorination and may suggest one-electron chemistry. Reduced enzyme is sensitive to oxidation with the molecular oxygen.This work was supported by a grant (DK 084186) from the National Institutes of Health (to S.E.R.)

Steady-state and pre-steady-state characterization of iodotyrosine deiodinase from human thyroid

244th National Meeting (2012)

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