Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have identified genomic clones and corresponding cDNAs that encode a putative peroxidase of Drosophila melanogaster. The gene (DmPO) appears as a single copy gene located on the third chromosome at position 89 D/E. It is interrupted by seven small introns and one unusually large 5' intron (about 11 kb). Sequence analysis of the cDNA showed an open reading frame of 690 amino acids resulting in a protein of 77 kDa. The deduced amino acid sequence reveals an overall homology to myeloeosinophil and thyroid peroxidase, a human superfamily of peroxidases.
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PMID:Molecular characterization of a putative peroxidase gene of Drosophila melanogaster. 148 87

The oxidation of veratryl alcohol (3,4-dimethoxybenzyl alcohol) by lignin peroxidase H2 from Phanerochaete chrysosporium and H2O2 was inhibited by 3-amino-1,2,4-triazole (AT). Inhibition was found to be competitive with respect to veratryl alcohol (K1 = 18 microM) and noncompetitive with respect to H2O2. Unlike bovine lactoperoxidase, catalase, and thyroid peroxidase, AT was not a suicide (mechanism based) inhibitor for lignin peroxidase H2. Binding studies revealed that lignin peroxidase H2 catalyzed insignificant binding of [14C]AT to the enzyme. Apparently AT is a poor substrate for lignin peroxidase H2 and is only slowly oxidized to form a yellow product in the presence of H2O2. The formation of the yellow product was shown to increase with increasing concentrations of veratryl alcohol, suggesting that an intermediate in the oxidation of veratryl alcohol is able to mediate the oxidation of AT. Extensive metabolism of AT to CO2 by the white rot fungus Phanerochaete chrysosporium (approximately 60% in 30 days) was also demonstrated.
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PMID:Inhibition of veratryl alcohol oxidase activity of lignin peroxidase H2 by 3-amino-1,2,4-triazole. 153 63

Cloned cDNA templates of thyroid peroxidase (TPO) have been used in conjunction with the polymerase chain reaction (PCR) to express selected segments of the thyroid microsomal/peroxidase antigen (TMA/TPO) as recombinant protein in E. coli. Six small, different recombinant fragments averaging 120 amino acid residues and one large fragment (269 amino acids) of TPO which together encompass 80% of the extracellular region of the molecule have been produced and autoantibody (aAb) binding sites analysed by immunoblotting. A minimum of six independent, sequential antigenic determinants have been localized on the recombinant proteins and these map to the amino terminal, the central core region and the carboxyl terminal of the TPO molecule. More accurately, the six antigenic sites reside on overlapping recombinant TPO preparations termed R1a + R1b (residues 1 to 160) R1c (residues 145 to 250), R2b (residues 457 to 589), R3a (residues 577-677), R3b (residues 657-767) and R3c (residues 737-845). The large fragment of TPO termed R3 (residues 577-845) encompassing R3a, R3b and R3c also reacts with the aAbs. Different sera from patients with autoimmune thyroid disease contain antibodies to TMA/TPO which differ in their fine specificity. The use of recombinant molecular biological techniques together with PCR to prepare small segments of a large autoantigen as recombinant protein will now allow studies to progress on autoepitope mapping of the precise amino acid sequences of the TPO molecule with the use of synthetic peptides.
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PMID:Mapping of autoantigenic epitopes on recombinant thyroid peroxidase fragments using the polymerase chain reaction. 171 75

Iodination of the isolated thyroglobulin (Tg) by peroxidase was compared with various Tg preparations obtained from patients with thyroid diseases. For the purpose, the iodination process was observed in the incubation medium containing Tg, iodide, H2O2-generating system, and thyroid peroxidase (TPO) or lactoperoxidase (LPO). During the incubation, iodination of Tg preparations increased gradually and reached a plateau after 90 min., and 5 min. incubation with 3mIU or 14mIU of TPO, respectively. The degree of iodination level at the plateau region was different in each Tg preparation, depending on the iodine content of the original starting (native) preparation before incubation. The iodination level of cancer Tg with a very low iodine content (less than 0.1%) was low compared with the normal Tg level (obtained from normal thyroid tissue which contained about 0.4% iodine). The above findings suggest the possible existence of some structural differences of Tg in terms of the susceptibility to the iodination between the preparations of normal and diseased Tgs. As far as the immunological aspect concerned, there was no significant difference in the affinity (avidity) of Tg with polyclonal anti-Tg antibody between the native Tg and the enzymatically iodinated one. These results suggest that the changes of iodine and thyroid hormone contents of Tg by in vitro iodination, has no significant effect on the immunological property of Tg molecule.
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PMID:[Enzymatic iodination of thyroglobulins obtained from patients with thyroid disease]. 175 39

The mechanism of organosulfur oxygenation by peroxidases [lactoperoxidase (LPX), chloroperoxidase, thyroid peroxidase, and horseradish peroxidase] and hydrogen peroxide was investigated by use of para-substituted thiobenzamides and thioanisoles. The rate constants for thiobenzamide oxygenation by LPX/H2O2 were found to correlate with calculated vertical ionization potentials, suggesting rate-limiting single-electron transfer between LPX compound I and the organosulfur substrate. The incorporation of oxygen from 18O-labeled hydrogen peroxide, water, and molecular oxygen into sulfoxides during peroxidase-catalyzed S-oxygenation reactions was determined by LC- and GC-MS. All peroxidases tested catalyzed essentially quantitative oxygen transfer from 18O-labeled hydrogen peroxide into thiobenzamide S-oxide, suggesting that oxygen rebound from the oxoferryl heme is tightly coupled with the initial electron transfer in the active site. Experiments using H2(18)O2, 18O2, and H2(18)O showed that LPX catalyzed approximately 85, 22, and 0% 18O-incorporation into thioanisole sulfoxide oxygen, respectively. These results are consistent with a active site controlled mechanism in which the protein radical form of LPX compound I is an intermediate in LPX-mediated sulfoxidation reactions.
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PMID:Peroxidase-catalyzed S-oxygenation: mechanism of oxygen transfer for lactoperoxidase. 189 13

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 thyroid plasma membrane contains a Ca2(+)-regulated NADPH-dependent H2O2 generating system which provides H2O2 for the thyroid peroxidase-catalyzed biosynthesis of thyroid hormones. The plasma membrane fraction contains a Ca2(+)-independent cytochrome c reductase activity which is not inhibited by superoxide dismutase. But it is not known whether H2O2 is produced directly from molecular oxygen (O2) or formed via dismutation of super-oxide anion (O2-). Indirect evidence from electron scavenger studies indicate that the H2O2 generating system does not liberate O2-, but studies using the modified peroxidase, diacetyldeuteroheme horseradish peroxidase, to detect O2- indicate that H2O2 is provided via the dismutation of O2-. The present results provide indirect evidence that the cytochrome c reductase activity is not a component of the NADPH-dependent H2O2 generator, since it was removed by washing the plasma membranes with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid without affecting H2O2 generation. Spectral studies with diacetyldeuteroheme-substituted horseradish peroxidase showed that the thyroid NADPH-dependent H2O2 generator does not catalyze superoxide anion formation. The O2- adduct compound (compound III) was formed but was completely inhibited by catalase, indicating that the initial product was H2O2. The rate of NADPH oxidation also increased in the presence of diacetylheme peroxidase. This increase was blocked by catalase and was greatly enhanced by superoxide dismutase. The O2- adduct compound (compound III) was produced in the presence of NADPH when glucose-glucose oxidase (which does not produce O2-) was used as the H2O2 generator. NADPH oxidation occurred simultaneously and was enhanced by superoxide dismutase. We conclude that O2- formation occurs in the presence of an H2O2 generator, diacetylheme peroxidase and NADPH, but that it is not the primary product of the H2O2 generator. We suggest that O2- formation results from oxidation of NADPH, catalyzed by the diacetylheme peroxidase compound I, producing NADP degree, which in turn reacts with O2 to give O2-.
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PMID:Mechanism of hydrogen peroxide formation catalyzed by NADPH oxidase in thyroid plasma membrane. 199 28

Thyroid peroxidase is a heme-containing, membrane-bound, glycoprotein enzyme that catalyzes iodination and coupling in the thyroid gland. It is also the antigen for microsomal autoantibodies that are commonly found in the serum of patients with autoimmune thyroid disease. We examined the effect of deglycosylation on the catalytic functions and the immunoreactivity of this enzyme. A highly purified, solubilized, large tryptic fragment of porcine thyroid peroxidase, retaining all of the N-linked glycosylation sites of the native enzyme and displaying full catalytic activity was used. It was deglycosylated by treatment with N-glycanase under nondenaturing conditions. The loss in relative molecular mass after treatment, determined by gel electrophoresis, was about 75% of the estimated molecular weight of the glycan portion of porcine thyroid peroxidase. Lectin blots performed with horseradish peroxidase-conjugated concanavalin A showed a similar loss in relative molecular mass but some residual carbohydrate. The intensity of the carbohydrate stain was consistent with the loss of about 75% of the glycans. Despite this loss, three different assays for catalytic activity of porcine thyroid peroxidase were not significantly decreased. Immunoreactivity measured by immunoblotting and by enzyme-linked immunosorbent assay was also unimpaired. These findings suggest that N-glycanase-sensitive glycans in porcine thyroid peroxidase do not act as antigenic determinants and play a minor role, if any, in catalytic activity and, presumably therefore, in the maintenance of protein conformation.
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PMID:Enzymatic deglycosylation of porcine thyroid peroxidase: effects on catalytic activity and immunoreactivity. 200 Jun 95

Insulin-dependent diabetes is associated with other autoimmune diseases and subclinical hypothyroidism has been reported in pregnant diabetic women. We studied the thyroid function of 85 women with diabetes during pregnancy and after delivery, as well as various autoantibodies. During pregnancy, thyroid microsomal antibodies were present in 17/85, antibodies against thyroid peroxidase in 16/85, thyroglobulin antibodies in 2/85, parietal cell antibodies in 23/85, adrenal antibodies in 4/77, rheumatoid factor in 15/85, and thyroid-stimulating antibodies in 43/85. Presence of antibodies was not combined with thyroid dysfunction, but TSH and HbA1c was increased (p less than 0.005) in women with thyroid antibodies. The gestational age of the infants was lower (p less than 0.01) in women with positive thyroid-stimulating antibody titre, whereas the ponderal index was only lower in those with peroxidase antibodies (p less than 0.05). After delivery, microsomal and peroxidase antibodies were positive in 10 (17.5%) of 57 patients followed. Six women developed postpartum thyroiditis (10.5%), of whom 5 were positive for both microsomal and peroxidase antibodies; two of those showing a hyperthyroid phase also had positive thyroid-stimulating antibody titre. We conclude that autoantibodies occur with increased incidence in pregnant diabetic women. Thyroid antibodies are related to a slightly reduced thyroid capacity and involve a high risk of postpartum thyroiditis. Further, thyroid antibodies seem to influence the nutritional status of the infant.
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PMID:Thyroid function and autoimmune manifestations in insulin-dependent diabetes mellitus during and after pregnancy. 202 11

We have reported that some anti-thyroid peroxidase antibodies inhibit the activity of thyroid peroxidase in vitro. These thyroid peroxidase activity-inhibiting immunoglobulins seem to inhibit thyroid function in some patients, but the relationship between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function is not simple. We designed this study to explore this lack of a simple relationship. We stained immunoglobulin G deposits by immunofluorescence staining or the peroxidase-antiperoxidase method, and stained endogenous thyroid peroxidase activity by enzyme histochemistry in thyroid sections. When cryostat thyroid sections were incubated with thyroid peroxidase activity-inhibiting immunoglobulins, immunoglobulin G deposits were seen as lines of stain on the apical border and as intracellular staining, and endogenous thyroid peroxidase activity was inhibited. In paraffin-embedded thyroid sections from 5 Hashimoto's patients and 6 Graves' patients, immunoglobulin G deposits were not found on the apical border of the follicular epithelium. In frozen thyroid sections from 22 Graves' patients, no clear deposits of immunoglobulin G on this apical border were seen. In organ-cultured thyroid slices incubated with thyroid peroxidase activity-inhibiting immunoglobulins, endogenous thyroid peroxidase activity was not inhibited. In conclusion, thyroid peroxidase activity-inhibiting immunoglobulins may reach its antigen only with difficulty. This is one of the reasons why no simple relationship is observed between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function.
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PMID:Why no simple relationship between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function in autoimmune thyroid disease? 203 41


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