Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroid hormone formation requires the coincident presence of peroxidase, H2O2, iodide, and acceptor protein at one anatomic locus in the cell. The peroxidase enzyme appears to be a protoporphyrin lX containing heme protein, with binding sites for both iodide and tyrosine. It is probable that both iodide and tyrosine are oxidized to free radical forms which unite to form iodotyrosine. The peroxidase is also involved through an uncertain mechanism in iodotyrosine coupling and probably in oxidation of sulfhydryl bonds in thyroglobulin. H2O2 may be supplied by microsomal NADPH-cytochrome c reductase or NADH-cytochrome b5 reductase. Other possible intracellular H2OI generating systems include monoamine oxidase and xanthine oxidase. The usual acceptor for iodide is thyroglobulin, which is currently believed to be iodinated within apical secretory vesicles at the cell border just prior to liberation into the colloid, or possibly after liberation into the colloid. Other soluble an insoluble proteins are also iodinated within the gland. The peroxidase is present in numerous cellular structures, but iodination activity occurs primarily, if not only, at the apical cell border. The controls of iodination are imperfectly known. Thyrotrophin modulation of iodide uptake, H2O2 generation, thyroglobulin synthesis, and peroxidase enzyme level obviously are the main regulations. Many of these actions are thought to involve mediation of adenyl cyclase and subsequent activation of intracellular phosphokinases. Antithyroid drugs of the thiocarbamide group are competitive inhibitors of iodination under some circumstances, but if much iodide is present, they react with the oxidized iodine intermediate and are irreversibly inactivated themselves. Clinical problems involving defective peroxidase function are among the most frequent hereditary defects of thyroid hormone formation. Recognized abnormalities include deficient peroxidase, abnormality in binding of the peroxidase apoprotein to its prosthetic group, and other less well-identified abnormalities in peroxidase structure and function. Peroxidase is typically elevated in thyroid tissue from patients with hyperthyroidism sometimes deficient in cold thyroid nodules, and frequently diminished in tissue from patients with Hashimoto's thyroiditis.
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PMID:Biosynthesis of thyroid hormone: basic and clinical aspects. 6 47

Cold thyroid nodules are generally due to impaired iodide uptake, while organification remains normal. In a case of a nodule appearing hot one hour after Tc99 m and cold 24 h after 131I-iodide, in vivo investigations showed that the trapping function was unimpaired and that the defect lay in organification. An early thyroid scan taken with 131I-iodide showed definite radioactivity in the nodule which was dischargeable by K perchlorate. This finding was confirmed by in vitro study of the tissue. Indirect evidence suggests that a defect was present in the H2O2 generating system rather than in peroxidase.
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PMID:Benign thyroid nodule with normal iodide trap and defective organification. 120 1

Exposure of cold-acclimatized rats to heat (37 degrees C) for a short period decreased brown adipose tissue (BAT) mitochondrial substrate-dependent oxygen uptake and H2O2 generation. Both the concentration and substrate-dependent rate of cytochrome b reduction decreased as early as 3 h of heat exposure. These results identify cytochrome b as the locus of regulation of electron transport in BAT mitochondria under conditions of heat stress.
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PMID:Regulation of respiratory activity of brown adipose tissue mitochondria through changes in cytochromes. 228 13

Exposure of rats to the cold (4-5 degrees C) caused large (2-3-fold) increases in the mass of interscapular brown adipose tissue (BAT), its mitochondrial content and the basal metabolic rate of the animals. The rate of substrate oxidation by BAT mitochondria also increased about 3-fold. When cold-acclimated animals were exposed to heat (37 degrees C), the BMR decreased by half in 3 h, the earliest time interval tested. Mitochondrial substrate oxidation, as well as substrate-dependent H2O2 generation, showed a proportionate decrease in rates. In these mitochondria, activities of cytochrome c reductases, but not dehydrogenases with NADH, alpha-glycerophosphate and succinate as substrates, also showed a significant decrease. The concentration of cytochromes aa3 and b, but not cytochrome c, also decreased in BAT mitochondria from 12-h heat-exposed animals, while the change in concentration of cytochrome b alone was found as early as 3 h of heat exposure. These results identify the change in cytochromes as a mechanism of regulation of oxidative activities in BAT mitochondria under conditions of acute heat stress.
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PMID:Decrease of oxidative activities in brown adipose tissue mitochondria of cold acclimated rats on short term exposure to heat stress. 237 58

In the feline intestine studies have implicated superoxide (O.-) and other oxygen derived free radicals as initiators of injury as measured by increased capillary permeability during the reperfusion period. Biochemical mechanisms of this free radical generation include: xanthine oxidase dependent O.- production, hydrogen peroxide (H2O2) formation by superoxide dismutase (SOD), hydroxyl radical (OH-) production via the Haber-Weiss reaction, and lipid radical formation from membrane peroxidation. Pathological consequences of these events include inflammatory neutrophil infiltration, damage to the collagen and mucosal basement membrane, increased capillary permeability, edema, cell degeneration and necrosis. Animal models of neonatal necrotizing enterocolitis (NNEC) indicate that intestinal injury occurs after the etiologic factors (hypothermia, hypoxia) are removed. In order to determine the role of active oxygen species in the pathogenesis of NNEC, weanling hamsters and neonatal piglets were cold stressed and activities of pro/antioxidant enzymes were determined, and histopathologic and ultrastructural studies were performed. Cold stressed weanling hamsters showed a 55.7% (P less than 0.05) decrease in xanthine dehydrogenase/xanthine oxidase activity ratio. Light microscopy revealed scattered colonic mucosal erosions and submucosal edema in 50% of cold stressed animals. Transmission electron microscopy demonstrated degeneration of colonic mucosal epithelial cells, enlarged intracellular spaces, cytoplasmic vacuolization, and nuclear membrane swelling. The colonic serosa was also edematous and infiltrated with bacteria. Large intestinal tissue from cold stressed neonatal piglets showed a significant increase (P less than 0.05) in Mn and Cu, Zn, SOD, CAT, GSH-Red, total GSH, and Glc6-PD at 0 and 12 hrs. post stress.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal post-ischemic reperfusion injury: studies with neonatal necrotizing enterocolitis. 259 24

Binding sites for horseradish peroxidase (HRP), with unusual properties, were detected on the surface of cultured and isolated cells after the cells (on cover slips) had been quickly dried, fixed in cold methanol, and post-fixed in a paraformaldehyde solution. The reaction for surface-bound HRP was suppressed by micromolar concentrations of glycoproteins such as invertase, equine luteinizing hormone (eLH) or human chorionic gonadotropin (hCG). The reaction was also suppressed by 20 mM CDP, UDP, GTP, NAD, and ribose 5-phosphate. Two to six times higher concentrations of GMP, fructose 1-phosphate, galactose 6-phosphate, mannose 6-phosphate, fructose 6-phosphate, and glucose 6-phosphate were required to suppress the binding reaction. AMP, ATP, heparin, mannan, and eight non-phosphorylated sugars showed relatively low competing potencies but fucoidin and alpha-lactalbumin were strong inhibitors. No addition of Ca2+ was required for the binding of HRP to the cell surface. However, calcium-depleted, inactive HRP did not compete with the binding of native (calcium-containing) HRP whereas H2O2-inactivated HRP suppressed the binding. GTP, NAD, ribose 5-phosphate, and EGTA accelerated the release of previously-bound HRP from the cell surface whereas glycoproteins (invertase, eLH, and hCG) did not do so. Addition of Ca2+ to GTP, NAD, ribose 5-phosphate or to EGTA prevented the accelerated release of HRP from the cell surface. It is suggested that calcium, present either in the surface membrane or in HRP itself, is involved in the binding of HRP to the cell surface and in the inhibition of binding by GTP, NAD, and ribose 5-phosphate. It is also suggested that alpha-lactalbumin, GTP, UDP, and CDP compete with the binding of HRP to a glycosyltransferase on the cell surface.
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PMID:Unusual binding sites for horseradish peroxidase on the surface of cultured and isolated mammalian cells. Suppression of binding by certain nucleotides and glycoproteins, and a role for calcium. 309 11

Antibodies were raised, in rabbits, against an arachidonate- and U46619-binding protein purified from calf platelets. Spectral measurements and immunodiffusion experiments were employed to follow conformational responses of the protein in relation to platelet activation. Upon treatment with the platelet agonists, arachidonate and PGH2, as well as the common haem ligands, imidazole and CN-, the purified protein had its Soret band red-shifted, with hypochromicity, but the protein saturated with the agonists, not with the haem ligands, showed altered antigenic properties in immunodiffusion experiments. In an analogous manner activation of gel-filtered calf platelets with high concentrations of ADP and A23187, as well as by cold, had Soret bands of extracts of sonicated platelets red-shifted, with hypochromicity; concomitantly, antigenically different conformations of the protein appeared in Triton X-100 extracts of the activated platelets. A protein immunologically related to the platelet protein was detected in Triton X-100 extracts of calf neutrophils. It is suggested that conformational changes of the protein induced by arachidonate or prostaglandin endoperoxides or H2O2 formed in different compartments during platelet activation by different stimuli may be a biochemical mechanism of stimulus-response coupling and that similar mechanisms might operate in other cell types.
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PMID:Conformational responses of an arachidonate- and U46619-binding haemoprotein in relation to platelet activation. 310 80

This is the first report on the generation of H2O2 by brown adipose tissue mitochondria. Flavin dehydrogenase-linked substrates like succinate, glycerol-1-phosphate, and fatty acyl CoA were good substrates for the reaction, while NAD+-linked substrates were less effective. In cold-acclimated animals the activity showed a substantial increase (2.5-fold). The Km and Vmax of the reaction were considerably lower than those of the respective dehydrogenase. Metal ions, particularly Cu2+ and Fe2+ were potent inhibitors of the reaction. Nucleoside diphosphates, which were inhibitors by themselves, potentiated the inhibitory action of Fe2+ ions. In most of the properties, the H2O2 generator of brown adipose tissue mitochondria resembled that of liver mitochondria.
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PMID:Generation of hydrogen peroxide by brown adipose tissue mitochondria. 362 19

Thyroid peroxidase in involved in several steps of the biosynthesis of thyroid hormone utilizing H2O2: peroxidation of iodide to iodine, iodination of thyroglobulin (Tg) and coupling reaction leading to T4 and T3 formation. The peroxidase enzyme appears to be an heme protein containing a protoporphyrin IX, with binding sites for both iodide and tyrosine. Although the peroxidase is present in numerous cellular structure, iodination activity occurs primarily if not only at all, at the apical cell border. Lack of peroxidase activity or abnormal peroxidase has been described in isolated cases of congenital goiter with organification defect and a positive perchlorate test. However no change in enzymatic activity has been found in patients with Pendred's syndrome as compared to normal tissue. The deficiency of hormone synthesis observed in various benign diffuse thyroid disorders in certainly not due to a lack of peroxidase activity. In treated hyperthyroid patients, a high cellular activity is observed, especially at the apical cell border. In euthyroid patients with diffuse sporadic goiter, an increase of peroxidase activity is also observed. However, the cytochemical localization of the enzyme in goitrous thyroid gland shows that the peroxidase activity is mostly visualized around numerous lipoid structures; being concentrated in this particular site, the enzyme might preferentially oxidize lipids and consequently be less available for hormone synthesis. In euthyroid hot nodule, the peroxidase activity is normal. In cold nodule, a discrepancy between iodide oxidation and protein iodination has been found, suggesting that iodide peroxidation and iodination of tyrosine residues of Tg are two relatively independent processes although thyroid peroxidase catalyses both reactions. In contrast with the benign pathological conditions, the peroxidase activity is lower than normal in thyroid cancerous tissue.
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PMID:[Peroxidase and human thyroid hormone synthesis disorders (author's transl)]. 626 13

Horseradish peroxidase (HRP), a glycoprotein rich in mannose groups, was used as a ligand to detect receptors for glycoproteins in formalin-fixed, frozen sections of rat liver. Specific binding of HRP occurred to surface membranes of sinusoidal cells but not to those of parenchymal cells. The binding sites were visualized after the peroxidatic reaction in erythrocytes had been suppressed by methanol-H2O2 and phenylhydrazine, the latter reagent also decreasing the nonspecific background adsorption of HRP. Several factors influencing the reaction were studied systematically. The specific binding of HRP to sinusoidal cells was greatly decreased or abolished when tissue blocks were fixed for longer than 1-2 h in a cold 4% formaldehyde solution and the frozen sections subsequently treated for 30 min in cold methanol. The specific binding of HRP increased when the concentration of HRP in the medium was increased from 10 microgram/ml to 40 microgram/ml, when the time of incubation with HRP was increased from 1 h to 4 h, or when the temperature of incubation with HRP was increased from 4 degrees C to 22 degrees C, the pH of the incubation medium was increased from 7.0 to 10.0. Little or no specific binding of HRP was observed in the absence of added Ca++. The binding of HRP was suppressed by 10 mM mannose or 0.004% mannan whereas the suppression of the binding reaction by galactose or galactan required 30-40 ties higher concentrations.
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PMID:Cytochemical detection of mannose-specific receptors for glycoproteins with horseradish peroxidase as a ligand. 627 29


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