H2o2

Tyrosines

Iodotyrosines

Thyronine y Nx Hormones

TPOoxid

Compound ©

TPOoxid Compound I

Compound 111

figure 6-9 Summary of reactions catalyzed by thyroid peroxidase (TPO) to generate iodotyrosines and thyroid hormones. Five separate reactions have been postulated, which can be separated into two phases. Phase A utilizes reactions 1-3 to generate iodotyrosine, while phase B utilizes reactions 4-6 to effect coupling of iodotyrosines to generate thyronine hormones. In phase A, reaction 1 utilizes H2Oz, which forms a complex with TPO, designated as compound I. Compound I can participate as a substrate in both reactions 2 and 3. Reaction 2 utilizes compound I to oxidize I so as to generate an active iodinating agent (shown here as either an iodinium ion or hypoiodate bound to TPO). Reaction 3 then catalyzes the iodination of tyrosine and regenerates TPO. In phase B, in the absence of iodide, reaction 4 effects the conversion of compound I into compound II. Next, reaction 5 catalyzes the coupling of two iodinated thyronines, which generates a thyronine hormone and regenerates free TPO (see Fig. 6-10). In the presence of excess H2O2, reaction 6 converts compound II into compound III, which is inactive; reaction 6 can be prevented by I. The chemical nature of compounds I, II, and III is not yet known. [Modified with permission from Gentile, F., DiLauro, R., and Salvatore, G. (1995). Biosynthesis and secretion of thyroid hormones. In "Endocrinology" (L. ]. DeGroot et al. eds.), Vol. 1, Chapt. 34, pp. 517-542. W. B. Saunders, Philadelphia, PA.]

Hormones, Second Edition

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