Re:Factors influencing the study of peroxidase-generated iodine species

December 8, 2008

1: Thyroid. 2008 Jul;18(7):769-74. Links

Factors influencing the study of peroxidase-generated iodine species and implications for thyroglobulin synthesis.

Kessler J, Obinger C, Eales G.

Symbollon Pharmaceuticals, Inc., Framingham, Massachusetts, USA. jackkessler@...

A key issue in the mechanism of thyroglobulin (Tg) iodination by

thyroperoxidase (TPO) is whether a TPO-bound iodine intermediate

directly iodinates Tg-incorporated tyrosines (specific iodination) or

whether reactive iodine species released from TPO effectuate Tg

iodination (nonspecific iodination). We addressed these alternatives by

(a) determining the aqueous equilibria of the iodine species

potentially involved in the kinetic studies of TPO-mediated iodination,

and ( reviewing the structure of the substrate channel in mammalian

peroxidases. Redox-potentiometric analysis of aqueous iodine combined

with integrated mathematical modelling demonstrates that I2 reacts with

water to form several iodine species including hypoiodious acid (HOI).

The HOI/I2 ratio depends on time, iodide concentration, buffering

agents, and pH varying dramatically from pH 4 to 7.4. These factors may

confound the use of is-Menten kinetics to determine the

mechanism of TPO-catalyzed iodination since both I2 and HOI iodinate

tyrosine but with different specificities and reaction rates.

Consequently there is as yet no conclusive kinetic evidence that

iodination occurs via formation of a TPO-bound iodinated intermediate.

Furthermore, knowledge of TPO structure, gained from X-ray

crystallographic studies indicates that access of Tg-bound tyrosyl

groups to the active site of TPO is not possible. Thus the emerging

conclusion is that the mechanism of Tg iodination is nonspecific. This

is consistent with the occurrence of thyroid hormone formation in

prevertebrate ascidians which exhibit TPO-like activity but lack the Tg

gene.

Recommended Posts