Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

In the microsomal fraction of thyroid glands, the temperature dependence of DPH fluorescence polarization showed a discontinuity in the range of 29-33 degrees C. The transition temperatures of DMPC, DPPC and DSPC are near to the observed for the microsomal fraction. So that, thyroid peroxidase (TPO) was incorporated into liposomes made with these phospholipids. When DPH was incorporated in this peroxidase-liposome complex, a less pronounced phase transition was observed in the profiles of temperature dependence of DPH polarization, and the incorporation of the enzyme decreased the Tc. Arrhenius plots of TPO incorporated into liposomes showed discontinuities at similar temperatures observed by fluorescence polarization. The decrease of transition temperature of liposomes induced by thyroid peroxidase incorporation suggests that this enzyme seems to need a fluid medium for its enzyme activity.
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PMID:Incorporation of bovine thyroid peroxidase in liposomes. 654 98

The peroxidase and FAD-containing monooxygenase activities of porcine thyroid subcellular preparations were measured and it was observed that FAD-containing monooxygenase activity was considerably lower than that of peroxidase. The end product of 1-methyl-2[14C]thioimidazole oxidation catalysed by thyroid peroxidase was confirmed to be 1-methylimidazole by mass spectrometry. In the presence of thyroid peroxidase 1-methyl-2-thioimidazole would appear initially to be oxidised to bis(1-methylimidazole)-2,2'-disulphide. The extent of oxidation was dependent on the iodide concentration in the reaction mixture.
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PMID:The role of porcine thyroid peroxidase and FAD-containing monooxygenase in the metabolism of 1-methyl-2-thioimidazole (methimazole). 665 20

Mechanisms that have been proposed for peroxidase-catalyzed iodination require the utilization of 1 mol of H2O2 for organic binding of 1 mol of iodide. When we measured the stoichiometry of this reaction using thyroid peroxidase or lactoperoxidase at pH 7.0, we consistently obtained a ratio less than 1.0. This was shown to be attributable to catalase-like activity of these enzymes, resulting in unproductive cleavage of H2O2. This catalatic activity was completely iodide-dependent. To elucidate the mechanism of the iodide-dependent catalatic activity, the effects of various agents were investigated. The major observations may be summarized as follows: 1) The catalatic activity was inhibited in the presence of an iodine acceptor such as tyrosine. 2) The pseudohalide, SCN-, could not replace I- as a promoter of catalatic activity. 3) The inhibitory effects of the thioureylene drugs, methimazole and carbimazole, on the iodide-dependent catalatic activity were very similar to those reported previously for thyroid peroxidase-catalyzed iodination. 4) High concentrations of I- inhibited the catalatic activity of thyroid peroxidase and lactoperoxidase in a manner similar to that described previously for peroxidase-catalyzed iodination. On the basis of these observations and other findings, we have proposed a scheme which offers a possible explanation for iodide-dependent catalatic activity of thyroid peroxidase and lactoperoxidase. Compound I of the peroxidases is represented as EO, and oxidation of I- by EO is postulated to form enzyme-bound hypoiodite, represented in our scheme as [EOI]-. We suggest that the latter can react with H2O2 in a catalase-like reaction, with evolution of O2. We postulate further that the same form of oxidized iodine is also involved in iodination of tyrosine, oxidation of thioureylene drugs, and oxidation of I-, and that inhibition of catalatic activity by these agents occurs through competition with H2O2 for oxidized iodine.
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PMID:Mechanism of iodide-dependent catalatic activity of thyroid peroxidase and lactoperoxidase. 670 30

The kinetics of iodination and oxidation of hog thyroglobulin were studied with purified hog thyroid peroxidase and the results were compared with the reactions of free tyrosine. From Lineweaver-Burk plots and on the basis of a value of 0.83 for delta epsilon mM at 289 nm/iodine atom incorporated, the rate constant for transfer of an assumed enzyme-bound iodinium cation to thyroglobulin was estimated to be 6.7 X 10(7) and 2.3 X 10(7) M-1 s-1 in native (iodine content = 1.0%) and more iodinated (iodine content = 1.2%) thyroglobulins, respectively. This iodine-transferring reaction was stimulated by iodothyronines, similarly as observed in the reaction with free tyrosine. The iodination of thyroglobulin was inhibited by GSH, the inhibition being competitive with thyroglobulin. Thyroglobulin was oxidized in the presence of a thyroid peroxidase system without giving any appreciable change in absorbance around 300 nm. From stopped flow data, the oxidation was concluded to occur by way of two-electron transfer and the rate constant for the reaction of thyroid peroxidase Compound I with thyroglobulin was estimated to be 1.0 X 10(7) M-1 s-1. The stopped flow kinetic pattern was similar to that observed on the reaction with free tyrosine and monoiodotyrosine. About 6 mol of hydrogen peroxide were consumed per mol of thyroglobulin. Thyroid peroxidase catalyzed thyroglobulin-mediated oxidation of GSH, but lactoperoxidase did not.
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PMID:Iodination and oxidation of thyroglobulin catalyzed by thyroid peroxidase. 670 40

1. A subcellular fractionation from bovine thyroid gland homogenate was carried out by differential centrifugation. The maximal peroxidase activity was found in the microsomal fraction. 2. The effect of non-proteolytic agents on the solubilization of the enzyme was studied. It was found that non-ionic detergents with Hydrophilic Lipophilic Balance (HLB) between 12 and 14, such as Triton X-100 and Brij 96, were the best solubilizing agents. 3. The effect of pH, ionic strength, time and temperature of incubation of the peroxidase solubilization was analyzed. 4. The thermodynamic parameters of the thermoinactivation of solubilized enzyme and the activation energy (Ea) of the peroxidase-catalyzed reaction were calculated. 5. The values obtained for these parameters were very similar to those of the plant peroxidases, suggesting a common catalytic mechanism, as Bardsley et al., Eur. J. Biochem. (1982) have pointed out. 6. However thyroid peroxidase does not undergo any reactivation as plant peroxidases do, due to the role of the hydrophobic interactions which hold the peroxidase bound to microsomal membranes in the thyroid glands.
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PMID:Non-proteolytic solubilization of bovine thyroid peroxidase: thermodynamic parameters of the thermoinactivation. 682 9

The mechanism of reversible and irreversible inhibition of thyroid peroxidase (TPO)-catalyzed iodination by thioureylene drugs was investigated using a model incubation system. The major observations may be summarized as follows. 1) TPO is inactivated by 1-methyl-2-mercaptoimidazole and propylthiouracil even in the presence of a relatively high concentration of iodide. The extent of this inactivation depends on the ratio of iodide to drug. 2) Spectral changes observed on oxidation of the drugs with the peroxidase-iodide system were very similar to those observed when the drugs were oxidized nonenzymatically with I3-. These findings support the view that oxidized iodine is an intermediate in TPO-catalyzed oxidation of the drugs. 3) Under conditions where TPO is largely inactivated, inhibition of iodination is complete and irreversible. Drug metabolism, on the other hand, occurs to a limited extent. 4) Under conditions where TPO is only partially inactivated, inhibition of iodination is transient (reversible). In this case, drug metabolism is extensive, and higher oxidation products (sulfate and sulfinic acid) are observed. Inhibition of iodination occurs only during the interval required to reduce the drug concentration to a low level. Thereafter, iodination may occur at a rate close to that observed in the absence of drug. Based on these and other observations, a scheme is presented to explain the mechanism of reversible and irreversible inhibition of iodination. In essence, the type of inhibition depends on the relative rates and extent of TPO inactivation and drug oxidation. These rates, in turn, depend primarily on the iodide to drug concentration ratio. A high ratio favors extensive drug oxidation and reversible inhibition. A low ratio favors TPO inactivation and irreversible inhibition.
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PMID:Reversible and irreversible inhibition of thyroid peroxidase-catalyzed iodination by thioureylene drugs. 684 36

The present study was undertaken to determine whether the thioureylene antithyroid drugs propylthiouracil [6-propyl-2-thiouracil (PTU)] and methylmercaptoimidazole [1-methyl-2-mercaptoimidazole (MMI)] have a specific inhibitory effect on the thyroid peroxidase (TPO)-catalyzed conversion of diiodotyrosine to T4 (coupling reaction) independent of their well known inhibitory effect on peroxidase-catalyzed iodination. We have employed model incubation systems containing highly purified TPO to examine this question. Most experiments were performed with a model iodination system containing TPO, low iodine thyroglobulin, [131]iodide, and glucose-glucose oxidase. Both PTU and MMI are effective inhibitors of iodination of this system at physiological concentrations, and the system is well suited for studying the simultaneous action of these drugs on iodination and coupling. The addition of graded doses of the drugs to the iodination system demonstrated a relatively greater inhibitory effect on iodothyronine than on iodotyrosine formation. However, this observation in itself does not establish a specific inhibitory effect on coupling, since the formation of T4 involves a reaction between two molecules of 3,5-diiodotyrosine (DIT). The rate of this reaction, therefore, is second order with respect to DIT concentration, and the inhibition of DIT formation by thioureylene drugs would be expected to result in a disproportionately greater reduction in T4 formation even id there were no selective inhibitory effect of the drugs on the coupling reaction. Under certain conditions of incubation, however, it was possible to demonstrate a significant inhibitory effect on T4 and T3 formation without any decrease (in fact, a slight increase) in diiodotyrosine formation. These observations indicate that, at least under some conditions, PTU and MMI can exert a specific inhibitory effect on the coupling reaction. In the case of PTU, a specific inhibitory effect on coupling was also demonstrated with an incubation system in which TPO-catalyzed coupling was measured in the absence of iodination.
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PMID:Preferential inhibition of thyroxine and 3,5,3'-triiodothyronine formation by propylthiouracil and methylmercaptoimidazole in thyroid peroxidase-catalyzed iodination of thyroglobulin. 705 83

A selective adsorbent for thyroid peroxidase was prepared by attaching tyrosine, a possible substrate of peroxidase, to agarose beads. When partially purified calf thyroid peroxidase was passed through a column containing this adsorbent, the peroxidase activity present was bound to the agarose. The binding of thyroid peroxidase on the adsorbent was inhibited by tyrosine and iodotyrosines. Quantitative elution was readily achieved by modifying the pH of eluting buffers. The peroxidase eluted at pH 8.5 or pH 9.8 was slowly inactivated. During this inactivation, enzyme activity assayed by triiodide formation was not affected, while peroxidase activity assayed by guaiacol oxidation and tyrosine iodination were slowly reduced. Enzyme activity was protected by elution under a partially anaerobic state. Iodide and guaiacol did not interfere with the adsorption of thyroid peroxidase by tyrosine residues on agarose. These data indicate the following characteristics of thyroid peroxidase. 1. Tyrosine and iodotyrosines are the substrates of thyroid peroxidase. 2. Thyroid peroxidase has specific active site(s) for tyrosine and iodide which are independent of each other. 3. The active site(s) for tyrosine and iodotyrosines are common. 4. The active site(s) for tyrosine and guaiacol are similar but are not identical. 5. Thyroid peroxidase is able to bind tyrosine before it is activated to "Complex I" by hydrogen peroxide.
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PMID:Affinity chromatography of thyroid peroxidase using tyrosine coupled to Agarose. 707 48

Stopped flow experiments were carried out with purified hog thyroid peroxidase (A413 nm/A280 nm = 0.42). In the steady state of oxidations of L- and D-tyrosines, N-acetyltyrosinamide, and monoiodotyrosine, thyroid peroxidase existed in the form of Compound I, the primary catalytic intermediate of peroxidase in its reaction with H2O2. Kinetic results led us to conclude that thyroid peroxidase catalyzes two-electron oxidations of these molecules. In the steady state of oxidation of diiodotyrosine, on the other hand, the enzyme was found in the form of compound II at pH 7.4, but in the form of compound I at pH 5.5. The result implies that the mechanism of diiodotyrosine oxidation varied from a one-electron to a two-electron type as the pH decreased. The selection of mechanisms of oxidation appears to be peculiar to thyroid peroxidase; horseradish peroxidase and lactoperoxidase catalyzed only one-electron oxidations of these five donor molecules. Rate constants for rate-limiting steps in the reactions of these donor molecules with the three peroxidases were measured by overall kinetic and stopped flow kinetic methods.
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PMID:One- and two-electron oxidations of tyrosine, monoiodotyrosine, and diiodotyrosine catalyzed by hog thyroid peroxidase. 714 55

1. The uterine peroxidase activity of rats was determined quantitatively at each stage of the estrous cycle, and it was found that the protein-based and DNA-based specific activities in proestrus and estrus are 4-5 times higher than those in diestrus. Ovariectomy caused a marked decrease in the activity in the uterus, and the administration of estrogen, but not other steroids, restored the activity. Of many organs in normal rats, the uterus had the greatest peroxidase activity. The peroxidase activity of pig uterus varied from animal to animal and the mean specific activity was about one-hundredth of that of rats. 2. The peroxidase activity of uterine tissue was mainly associated with subcellular particulates, especially microsomal fractions. The membrane-bound peroxidase showed a cyanide-difference spectrum which was very similar to those of lactoperoxidase and thyroid peroxidase. 3. Rat uterine fluid peroxidase was also found to be estrogen-dependent and to exhibit a similar cyanide-difference spectrum. 4. On the basis of spectroscopic, kinetic, and other properties, the relationship between the uterine tissue peroxidase, uterine fluid peroxidase and eosinophil peroxidase is discussed.
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PMID:Comparative studies on estrogen-dependent peroxidases contained in uterine microsomes and fluid of rats and pigs. 719 35


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