The Role of Lactoperoxidase‐H2O2 Compounds in the Catalysis of Thyroglobulin Iodination and Thyroid Hormone Synthesis

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Abstract
Lactoperoxidase catalyzes successively, as thyroid peroxidase, the iodination of several tyrosyl residues of thyroglobulin and the coupling of some of them to thyroid hormones. We show the following results in this paper. The iodination reaction is catalyzed by lactoperoxidase compound I whereas lactoperoxidase ‘compound II’ catalyzes the coupling reaction. Lactoperoxidase compound III catalyzes neither reaction. Titration of lactoperoxidase ‘compound II’ by ferrocyanide showed that this enzyme‐H2O2 species is two oxidizing equivalents above the native enzyme, and therefore constitutes a second form of lactoperoxidase ‘compound I’. These two forms of lactoperoxidase ‘compound I’ differ probably from one another in the localization of one of the two oxidizing equivalents either on porphyrin ring: π‐compound I (compound I), or on the apoprotein: R°‐compound 1 (‘compound II’). The difference in specificity between π‐compound I and R°‐compound I in catalyzing the iodination and the coupling reaction respectively, might therefore depend differences both in the distribution of the two oxidizing equivalents and in the structure of the substrates. In the presence of free diiodotyrosine, a halophenol which stimulates at very low concentrations the coupling reaction but has no effect on the iodination reaction, the transfer of electrons between the substrate and lactoperoxidase R°‐compound I is nearly stoichiometric: 1 mole of hormone is produced for each mole of lacto‐peroxidase R°‐compound I. Thus free diiodotyrosine seems to play the role of a very specific co‐factor of the coupling reaction. Iodide and SCN− also stimulate the coupling reaction when the H2O2/enzyme ratio used to prepare lactoperoxidase R°‐compound I is higher than one. They do so by preventing the accumulation of the inactive derivative of lactoperoxidase, compound III, which is formed in the presence of excess H2O2. Iodide prevents the formation of compound III whereas SCN− very rapidly decomposes compound III back to the native enzyme.