Thiourea and Cyanamide as Inhibitors of Thyroid Peroxidase: The Role of Iodide*

Davidson, Bert J.; Soodak, Morris; Strout, H V; Neary, Joseph T.; Nakamura, Charles E.; Maloof, Farahe

doi:10.1210/endo-104-4-919

Cited by 38 publications

(14 citation statements)

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“…Although cyanide and aminotriazole can directly inhibit myeloperoxidase, they can also react with HOC1 (30). It should be noted that a variety of peroxidase inhibitors seem to mediate their effects by interacting with the activated halide rather than directly with the enzyme (33,34). Finally, a Cl-requirement was based on the inhibitory effects of Cl--free conditions on chloramine formation.…”

Section: Discussionmentioning

confidence: 99%

Chlorination of Taurine by Human Neutrophils

Weiss¹,

Klein²,

Slivka³

et al. 1982

J. Clin. Invest.

750

237

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A B S T R A C T The model hydrogen peroxide-myeloperoxidase-chloride system is capable of generating the powerful oxidant hypochlorous acid, which can be quantitated by trapping the generated species with the ,-amino acid, taurine. The resultant stable product, taurine chloramine, can be quantitated by its ability to oxidize the sulfhydryl compound, 5-thio-2-nitrobenzoic acid to the disulfide,5,5'-dithiobis(2-nitrobenzoic acid) or to oxidize iodide to iodine. Using this system, purified myeloperoxidase in the presence of chloride and taurine converted stoichiometric quantities of hydrogen peroxide to taurine chloramine. Chloramine generation was absolutely dependent on hydrogen peroxide, myeloperoxidase, and chloride and could be inhibited by catalase, myeloperoxidase inhibitors, or chloride-free conditions. In the presence of taurine, intact human neutrophils stimulated with either phorbol myristate acetate or opsonized zymosan particles generated a stable species capable of oxidizing 5-thio-2-nitrobenzoic acid or iodide. Resting cells did not form this species. The oxidant formed by the stimulated neutrophils was identified as taurine chloramine by both ultraviolet spectrophotometry and electrophoresis. Taurine chloramine formation by the neutrophil was dependent on the taurine concentration, time, and cell number. Neutrophil-dependent chloramine generation was inhibited by catalase, the myeloperoxidase inhibitors, azide, cyanide, or aminotriazole and by chloride-free conditions, but not by superoxide dismutase or hydroxyl radical scavengers. Thus, it appears that stimulated human neutrophils can utilize the hydrogen peroxide-myeloperoxidasechloride system to generate taurine chloramine. Based on the demonstrated ability of the myeloperoxidase Drs. Klein, Slivka, and Wei completed this work in partial fulfillment of an Honors Degree from the University of Michigan.

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Section: Discussionmentioning

confidence: 99%

Chlorination of Taurine by Human Neutrophils

Weiss¹,

Klein²,

Slivka³

et al. 1982

J. Clin. Invest.

750

237

View full text Add to dashboard Cite

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“…As previously mentioned, the reaction between iodide and H 2 O 2 generally requires a peroxidase catalyst (Luther et al, 1995). We therefore examined the effects of thiourea and aminotriazole, two peroxidase inhibitors (Wood and Legg, 1970;Davidson et al, 1979), on iodide accumulation. We found a statistically significant decrease in larval iodine influx with increasing thiourea concentration (from 1 to 1000nmoll -1 ) during a 30min incubation (F 4,2 =6.16,P<0.05;Table2).…”

Section: Sodium-independent Iodine Uptake Mechanismsmentioning

confidence: 99%

Iodine accumulation in sea urchin larvae is dependent on peroxide

Miller

Heyland

2012

Journal of Experimental Biology

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SUMMARYIodine has many important biological functions and its concentrations vary with the environment. Recent research has provided novel insights into iodine uptake mechanisms in marine bacteria and kelp through hydrogen peroxide-dependent diffusion (PDD). This mechanism is distinct from sodium-dependent mechanisms known from vertebrates. In vertebrates, iodine accumulates in the thyroid gland by the action of the apical iodide transporter (AIT) and the sodium/iodide symporter (NIS). Neither of these proteins has, thus far, been identified outside of the chordates, and PDD (as an iodine uptake mechanism) has never been studied in animals. Using 125 I as a marker for total iodine influx, we tested iodine uptake via sodium-dependent transport versus PDD in embryos and larvae of the sea urchin Strongylocentrotus purpuratus. We found that iodine uptake in S. purpuratus is largely independent of NIS/AIT. Instead, we found that uptake is dependent on the presence and production of hydrogen peroxide, indicating that sea urchin larvae use PDD as a mechanism for iodine acquisition. Our data, for the first time, provide conclusive evidence for this mechanism in an animal. Furthermore, our data provide preliminary evidence that sodium-dependent iodine uptake via active transporter proteins is a synapomorphy of vertebrates. Supplementary material available online at

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“…Thiourea as well as a series of 35 different derivatives of this compound have already been shown to be potent inhibitors of different peroxidases [57, 116]. The ability to inhibit peroxidase activity has been demonstrated to be very strong in the case of some thiourea derivatives such as o -phenetylthiourea, which inhibits horseradish peroxidase 6 times more strongly than the parental compound [57].…”

Section: Peroxidase-mediated Mechanismsmentioning

confidence: 99%

Peroxidase-Mediated Mechanisms Are Involved in the Melanocytotoxic and Melanogenesis-Inhibiting Effects of Chemical Agents

Kasraee¹

2002

Dermatology

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Melanogenesis is based on the enzymatic conversion of the amino acid tyrosine, through a series of intermediates, to melanin pigments. The nature of the enzymes involved in the different steps of melanogenesis has been intensely debated. However, it is now believed that tyrosinase is responsible for the conversion of tyrosine to dopa and of dopa to dopaquinone, and that peroxidase accomplishes the oxidative polymerization of the eventually formed indoles to eumelanin pigments. Some very few investigators have also considered a main role for peroxidase in initiating melanogenesis. At present, most different hypotheses are focused on tyrosinase-mediated mechanisms to elucidate the melanocytotoxic and depigmenting activities of chemicals. However, many properties of these agents cannot be explained by such mechanisms. Most of the melanocytotoxic agents (e.g. hydroquinone, catechols, butylated hydroxyanisole) can be converted to cytotoxic species, such as quinones, by the peroxidase-H₂O₂ system. On the other hand, many of the melanogenesis inhibitors which are not known to inhibit tyrosinase (e.g. glucocorticoids, ascorbic acid, indomethacin) have the capacity to strongly inhibit peroxidase activity. We have proposed that peroxidase-mediated mechanisms, in addition to or in several instances rather than tyrosinase-mediated mechanisms, can explain the melanocytotoxic and depigmenting properties of such agents.

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Thiourea and Cyanamide as Inhibitors of Thyroid Peroxidase: The Role of Iodide*

Cited by 38 publications

References 0 publications

Chlorination of Taurine by Human Neutrophils

Chlorination of Taurine by Human Neutrophils

Iodine accumulation in sea urchin larvae is dependent on peroxide

Peroxidase-Mediated Mechanisms Are Involved in the Melanocytotoxic and Melanogenesis-Inhibiting Effects of Chemical Agents

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