Peroxidases are widely distributed throughout plants, animals, and microorganisms and carry out a variety of biosynthetic and degradative functions related to the consumption of hydrogen peroxide. Free radicals are produced during this reaction and can bind irreversibly to DNA, which is thought to be a cause of tumorigenesis. The similarity of the peroxidative reaction to one of a series of steps in the reaction of cytochrome P450 with substrates has been well documented. This may suggest the evolutionary relationship between cytochrome P450s and peroxidases. Studies on the structure-function relation of peroxidases, therefore, will help in the understanding of cytochrome P450s. In the case of animals, thyroid peroxidase and myeloperoxidase are the most well-studied peroxidases. Thyroid peroxidase is involved in thyroid hormone synthesis and recently has been indicated to be one of the major antigens of thyroid autoimmune diseases such as Graves' disease and Hashimoto's thyroiditis. On the other hand, myeloperoxidase is involved in bacteriocidal function of leukocytes and has completely different physicochemical properties from those of thyroid peroxidase. We have successfully cloned human thyroid peroxidase. The comparison of its deduced, amino acid sequence with that of the recently reported human myeloperoxidase revealed a surprising fact that both enzymes are diverged from a common ancestral gene and belong to the same gene family. We further isolated and partially sequenced genomic clones of human thyroid peroxidase and found that several exon-intron junctions are well conserved between two enzymes.
