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H Niepomniszcze

Publications and source records attributed to H Niepomniszcze.

6 recordsLinked to original sources
PubMed1977

Biosynthesis of thyroid hormone: basic and clinical aspects.

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.

Animals↗
PubMed1977

Familial goitre with partial iodine organification defect, lack of thyroglobulin, and high levels of thyroid peroxidase.

From a sibship of three sisters having congenital goitre and normal hearing, two had impairment of organification of iodine. S1 (4 years old) had goitre since birth, euthyroidism, and a negative perchlorate test. S2 (15 years old) and S3 (13 years old) were hypothyroid, and had radioiodide discharge after potassium perchlorate administration of 19.8% and 26.1%, respectively. Thyroid tissue was obtained at thyroidectomy. Peroxidase activity, in the thyroidal subcellular particles, was found to be qualitatively normal, but quantitatively increased. In the triiodide assay, the activity was: S1 6912 u, S2 2590 u, and S3 3844 u (normal values 900-1700 u). In the tyrosine-iodinase assay, the activities, expressed as nmoles of iodide incorporation per gram of tissue, were S1 1046, S2 471 (normal values 220-410). The activity of the thyroidal NADPH-cytochrome c reductase, an enzyme possibly involved in hydrogen peroxide generation, was: S1 0.084, S2 0.047, and S3 0.005 (normal values 0.018 muEq/min/mg). No thyroglobulin was detected by analytical ultracentrifugation, polyacrylamide gel electrophoresis, or double immunodiffusion in agar of the supernatant fractions. In patient S2, whose gland was labelled in vivo with 125I, 60% of the total radioactivity of the gland (pooled nodular and paranodular specimens) was in a particulate iodoprotein that was solublilized by trypsin, deoxycholate or digitonin. In the soluble fraction there were two iodoproteins: iodalbumin, and a second iodoprotein similar to the solubilized particulate iodoprotein. It is postulated that absence of the normal thyroidal receptor protein might be in some cases a cause of iodine organification defect.

Adolescent↗
PubMed1977

Effects of amiodarone on thyroid iodine metabolism in vitro.

Since alterations of thyroid function have been reported in patients treated with amiodarone, 2-butyl,3-(4-diethylaminoethoxy-3,4-diiodo, benzoyl) benzufuran, the effects of this drug on the active iodide transport, organic iodine formation, thyroid peroxidase and the enzymatic iodotyrosine deiodination, were studied. In pig thyroid slices the iodide transport was affected by amiodarone at concentrations of 10(-4) M and 10(-5) M, showing a decrease of T/M (tissue/medium) ratios of 20% and 23%, respectively. Lower concentrations produced no significant differences from the controls. Iodotyrosine synthesis was only, but poorly, affected by 10(-4) M and 10(-5) M amiodarone. Inhibition of the DIT formation was greater than that produced for MIT. Thyroid peroxidase activity, as measured by the tyrosine-iodinase assay, showed a 20% decrease at 10(-3) M amiodarone. None of the other concentrations have affected the activity of the enzyme, except for 7% at a concentrations of 10(-4) M. The iodotyrosine deiodination was affected by amiodarone only at a concentration of 10(-3) M and 10(-4) M. The inhibitions were of 22.5% and 16.8%, respectively. We have concluded that, under the conditions of our study, amiodarone per se does not affect the intrathyroidal iodine metabolism in concentrations which are usually present in the sera of patients treated with this drug. However, it is not possible to rule out an in vivo direct action, if amiodarone is substantially concentrated in the human thyroid gland.

Amiodarone↗
PubMed1975

Differentiation of two abnormalities in thyroid peroxidase causing organification defect and goitrous hypothyroidism.

Clinical and laboratory evaluations are reported on two patients with congenital goiter and hypothyroidism due to iodide organification defect. In one patient, a 31-year-old white male with severe mental retardation, administration of perchlorate caused discharge of 69% of the radioiodine accumulated in the thyroid gland. Thyroid tissue had negligible peroxidase activity in the tyrosine-iodinase, triliodide, and guaiacol assays. Preincubation of subcellular fractions with hematin restored activity. The restored enzyme was labile to high concentrations of H2O2 (5.6times 10-4 h2o2 produced inhibition in the triiodide assay). Heating of the enzyme for 5 min at 46 degrees C produced 50% inactivation, while higher temperatures were required to half-inactivate normal peroxidases. This case represents a second example of the "peroxidase apoenzyme-prosthetic group defect" causing congenital goiter. The second patient, an example of the "deficient peroxidase defect," was a 10-yr-old girl with 35% discharge of thyroidal radioiodine by perchlorate. Peroxidase activity in the goiter tissue was quantitatively decreased (10%-20% of normal values) but kinetically normal with respect to apparent Km for H2O2. Hematin had little effect on the enzyme. Peroxidase activity had abnormal subcellular distribution, since pellets sedimenting between 39,000 and 105,000 g contained most of the activity. Normal thyroglobulin was observed in the thyroid gland of the patient. Two distinct defects of the peroxidase system can produce congenital goiter by limiting organification of iodide.

Adult↗