Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.11.1.8 (thyroid peroxidase)
 3,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myeloperoxidase (MPO), which displays considerable amino acid sequence homology with thyroid peroxidase (TPO) and lactoperoxidase (LPO), was tested for its ability to catalyze iodination of thyroglobulin and coupling of two diiodotyrosyl residues within thyroglobulin to form thyroxine. After 1 min of incubation in a system containing goiter thyroglobulin, I-, and H2O2, the pH optimum of MPO-catalyzed iodination was markedly acidic (approximately 4.0), compared to LPO (approximately 5.4) and TPO (approximately 6.6). The presence of 0.1 N Cl- or Br- shifted the pH optimum for MPO to about 5.4 but had little or no effect on TPO- or LPO-catalyzed iodination. At pH 5.4, 0.1 N Cl- and 0.1 N Br- had a marked stimulatory effect on MPO-catalyzed iodination. At pH 4.0, however, iodinating activity of MPO was almost completely inhibited by 0.1 N Cl- or Br-. Inhibition of chlorinating activity of MPO by Cl- at pH 4.0 has been previously described. When iodination of goiter thyroglobulin was performed with MPO plus the H2O2 generating system, glucose-glucose oxidase, at pH 7.0, the iodinating activity was markedly increased by 0.1 N Cl-. Under these conditions iodination and thyroxine formation were comparable to values observed with TPO. MPO and TPO were also compared for coupling activity in a system that measures coupling of diiodotyrosyl residues in thyroglobulin in the absence of iodination. MPO displayed very significant coupling activity, and, like TPO, this activity was stimulated by a low concentration of free diiodotyrosine (1 microM). The thioureylene drugs, propylthiouracil and methimazole, inhibited MPO-catalyzed iodination both reversibly and irreversibly, in a manner similar to that previously described for TPO-catalyzed iodination.
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PMID:Myeloperoxidase-catalyzed iodination and coupling. 131 92

C57BL/6 mice show thyroid lesions when immunized with porcine thyroid peroxidase (pTPO) emulsified in CFA. We attempted to clarify a thyroiditogenic epitope on pTPO. Thyroid peroxidase treated with cyanogen bromide was fractionated by reverse phase chromatography, and six fractions (A to F) were obtained. Two of these fractions (D and E) stimulated lymph node cells (LNC) primed with pTPO in vitro and induced thyroiditis in vivo. Tricine-SDS-PAGE and rechromatography showed that fraction D consisted solely of a fragment of Mr 9500 Da and that fraction E contained mainly fragments of Mr of 5400 and 9500 Da. The fragment of fraction D was rechromatographed and 20 NH2-terminal amino acids were analyzed. This segment was found to correspond to residue 726-745 of pTPO deduced from cDNA at a probability of 80%. Four peptides ranging from residue 746-827 were first synthesized and tested for their thyroiditogenicity. Only Pep-2 (29 amino acids) could stimulate LNC primed with pTPO and induce thyroiditis. Pep-2 was divided into two smaller peptides (Pep-2-1 and -2-2) and their thyroiditogenicity was tested again. Pep-2-1 corresponding to residue 774-788, GPA-QITCTPRGWDSP, had thyroiditogenicity as well as the ability to stimulate LNC. It was thought that this segment was at least one of the thyroiditogenic epitopes on porcine thyroid peroxidase for C57BL/6 mice.
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PMID:Identification of thyroiditogenic epitope on porcine thyroid peroxidase for C57BL/6 mice. 137 23

A recent paper (Buchberger, W., 1988, J. Chromatogr. 432, 57) on lactoperoxidase-catalyzed bromination of tyrosine and thyroglobulin stated, without evidence, that thyroid peroxidase (TPO) is able to use bromide as a substrate. This was in disagreement with unpublished experiments previously performed in this laboratory, and we undertook, therefore, to examine this subject further. Highly purified porcine TPO was compared with lactoperoxidase (LPO) and chloroperoxidase (CPO) for ability to catalyze bromination of tyrosine, thyroglobulin, and bovine serum albumin (BSA). The incubation mixture contained 50-100 nM peroxidase, 10-500 microM 82Br-, tyrosine (150 microM), thyroglobulin (0.3 or 1 microM), or BSA (7.5 microM), and a source of H2O2. The latter was either generated by glucose (1 mg/ml)-glucose oxidase (0.5 or 1 micrograms/ml), or added initially as a bolus (100 microM). With TPO, formation of organically bound 82Br was undetectable under all conditions in the pH range 5.4-7.0. Lactoperoxidase and CPO, on the other hand, displayed considerable brominating activity. Lactoperoxidase was much more active at pH 5.4 than at pH 7.0 and was more active with BSA as acceptor than with tyrosine or thyroglobulin. The distribution of 82Br among the various amino acids in LPO-brominated thyroglobulin and BSA was determined by HPLC. As expected, monobromotyrosine and dibromotyrosine together comprised the greatest part of the bound 82Br. However, a surprisingly high percentage (20-25%) was present as monobromohistidine. Evidence was also obtained for the presence of a small percentage of the bound 82Br as tetrabromothyronine. Peroxidase-catalyzed bromination probably depends on the oxidation of Br- to Br+ by the Compound I form of the enzyme. Since oxidation of Br- to Br+ requires a stronger oxidant than oxidation of I- to I+, our results suggest that Compound I of LPO and of CPO has a higher oxidation potential than Compound I of TPO. In vivo experiments with rats on a low iodine diet injected with 82Br- showed that even under conditions of high stimulation by thyrotropic hormone, there is negligible formation of organic bromine in the thyroid. Measurements of thyroid:serum concentration ratios for 82Br- in similar rats provided no evidence that Br- is a substrate for the iodide transport system of the thyroid.
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PMID:Peroxidase-catalyzed bromination of tyrosine, thyroglobulin, and bovine serum albumin: comparison of thyroid peroxidase and lactoperoxidase. 189 6

the effects of iodide, thiocyanate and perchlorate, three anions with the same molecular size, on the oxidation of tyrosine to 3,3'-bityrosine by several peroxidases were evaluated at pH 8.8, i.e. in conditions in which iodide is not oxidized. The following results were obtained: 1. Iodide greatly stimulates the rate of bityrosine formation in the presence of thyroid peroxidase. No effect was seen with horseradish peroxidase or lactoperoxidase. Maximal iodide effects were obtained with about 0.5 mM iodide and Km for iodide was equal to about 0.028 mM. These results suggest that thyroid peroxidase contains a simple class of regulatory binding sites for iodide. 2. SCN- mimics iodide effects; maximal stimulatory effects were seen with about 0.5 mM thiocyanate and Km for SCN- was equal to 0.1 mM. The effects of SCN- and those of iodide were not additive. These results suggest that SCN- binds to the same regulatory site as iodide but with a slightly lower affinity. No effect of SCN- was seen with horseradish peroxidase or lactoperoxidase. 3. ClO-4, another anion with the same molecular size as iodide and SCN-, had neither an effect on the oxidation of tyrosine to bityrosine nor did it prevent the stimulatory effect of iodide on this reaction. Bromide was without effect on the same reaction.
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PMID:Regulatory effects of iodide and thiocyanate on tyrosine oxidation catalyzed by thyroid peroxidase. 739 41

The effect of retinoic acid (RA) on thyroid peroxidase (TPO) and thyroglobulin (Tg) gene expression was investigated in cultured human thyrocytes. Thyrocytes dispersed from Graves' thyroid tissues were incubated with TSH 5mU/ml and RA 0, 0.01, 0.1, 1.0 microM for 72 h respectively. The samples were then subjected to Northern gel analysis. Northern gel analysis using the specific cDNA probes showed that RA suppressed the accumulation of TPO and Tg mRNA stimulated by TSH in a time- and dose-responsive manner. Furthermore, RA inhibited forskolin and 8-Bromo-cyclic-AMP-induced TPO and Tg gene expression, suggesting a distal action site for these cAMP mediated gene expressions. Immunoprecipitation analysis using the specific monoclonal antibodies showed that TSH increased newly synthesized 100, 75, 36-kDa [35S] TPO. The increased de novo TPO was markedly inhibited by RA. Tg secretion from monolayer cultures was measured by radioimmunoassay. RA also inhibited TSH-induced Tg secretion in a dose dependent manner. RA did not affect [3H] thymidine uptake into primary cultured human thyrocytes. In conclusion, RA inhibits the synthesis of TPO and Tg via the suppression of thyroid-specific gene expression although the exact site of RA action on these genes in human thyroids remains to be further elucidated. These results suggest that RA may play a regulatory role in Tg and TPO gene expression, subsequently resulting in the suppression of thyroid hormone synthesis.
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PMID:Retinoic acid inhibits human thyroid peroxidase and thyroglobulin gene expression in cultured human thyrocytes. 846 54

Genotype and allele frequencies at seven Variable Number of Tandem Repeats (VNTR) loci currently used for forensic purposes have been estimated in a population sample from Calabria (south Italy). DNA target regions relevant to four microsatellites (THO.1; REN.4; D12S67; DYS19) and three minisatellites (D1S80; 3'APOB; TPO.10) were amplified by Polymerase Chain Reaction (PCR) and analysed by electrophoresis and ethidium bromide or silver staining. For all loci, the observed genotypes were found to be in agreement with those expected by the Hardy-Weinberg equilibrium. Data on allele frequencies were in line with those found in sample groups from northern or central Italy, tested for some of the above polymorphisms.
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PMID:Allele frequency distributions at seven DNA hypervariable loci in a population sample from Calabria (southern Italy). 904 23

Myeloperoxidase (MPO), eosinophil peroxidase, lactoperoxidase, and thyroid peroxidase are heme-containing oxidoreductases (EC 1.7.1.11), which bind ligands and/or undergo a series of redox reactions. Though sharing functional and structural homology, reflecting their phylogenetic origin, differences are observed regarding their spectral features, substrate specificities, redox properties, and kinetics of interconversion of the relevant redox intermediates ferric and ferrous peroxidase, compound I, compound II, and compound III. Depending on substrate availability, these heme enzymes path through the halogenation cycle and/or the peroxidase cycle and/or act as poor (pseudo-)catalases. Based on the published crystal structures of free MPO and its complexes with cyanide, bromide and thiocyanate as well as on sequence analysis and modeling, we critically discuss structure-function relationships. This analysis highlights similarities and distinguishing features within the mammalian peroxidases and intents to provide the molecular and enzymatic basis to understand the prominent role of these heme enzymes in host defense against infection, hormone biosynthesis, and pathogenesis.
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PMID:Active site structure and catalytic mechanisms of human peroxidases. 1628 70