Possible role of ascorbic acid as a physiological depressant of thyroxine degradation in rat liver

Yamamoto, Kiyoshi

doi:10.1016/0016-6480(64)90005-x

Cited by 3 publications

(3 citation statements)

References 15 publications

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“…The inhibitor also appeared to be responsible for the relative heat stability, pH dependence, and substrate inhibition of the system because all three effects disappeared after the inhibitor was removed by dialysis. The heat stability of deiodinase preparations has been reported by others (Stanbury et al, 1960;Yamamoto, 1964;Lissitzky et al, 1956;Gallon and Ingbar, 1966), and it has been used to challenge the enzymatic nature of the system. However, in view of the marked heat instability of the dialyzed enzyme, it is probable that the inhibitor was responsible for the heat stability observed in crude enzyme preparations.…”

Section: Discussionmentioning

confidence: 86%

“…Since then, various aspects of the reaction have been studied, but the published results and conclusions are confusing. An inhibitor that prevents the deiodination reaction from following established enzyme kinetic theory is probably the major cause of this confusion (Stanbury et al, 1960; Wynn and Gibbs, 1962;Nakagawa and Ruegamer, 1964;Yamamoto, 1964). However, a wide variation in substrate concentrations, pH optima, enzyme sources, cofactors, and assay techniques were used, and both enzymatic and nonenzymatic deiodination were observed.…”

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confidence: 99%

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Properties of a Rat Tissue Iodothyronine Deiodinase and Its Natural Inhibitor^*

Nakagawa¹,

Ruegamer²

1967

Biochemistry

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B-ring deiodination of L-thyroxine (T4) and L-triiodothyronine (Ta) by rat liver is enzymatic in nature, but the deiodinase activity in crude tissue homogenates is largely blocked by a naturally occurring inhibitor. The inhibitor is responsible for the time lag observed before deiodination takes place, and it is also responsible for the relative heat stability, pH dependence, and substrate inhibition of the system. All of these effects disappeared after the inhibitor was removed by dialysis. The specific activity of deiodinase was highest in liver, kidney, and heart microsomes, and the concentration of deiodinase remained the same in tissues of hypo-, eu-, and hyperthyroid animals. However, tissue levels of the inhibitor were highest in hypothyroid and lowest in hyperthyroid animals, suggesting that the natural inhibitor may play some role in metabolic control. The natural T he earliest report of an in citro system for the enzymatic deiodination of L-thyroxine (T4) and Ltriiodothyronine (T3) was published in 1955 by Sprott and Maclagan. Since then, various aspects of the reaction have been studied, but the published results and conclusions are confusing. An inhibitor that prevents the deiodination reaction from following established enzyme kinetic theory is probably the major cause of this confusion (Stanbury et al., 1960;Wynn and Gibbs, 1962;Nakagawa and Ruegamer, 1964;Yamamoto, 1964). However, a wide variation in substrate concentrations, pH optima, enzyme sources, cofactors, and assay techniques were used, and both enzymatic and nonenzymatic deiodination were observed. It has been suggested that some of the deiodination systems described may be artifactual (Job-Buzo et al., 1966). In view of the current lack of clarity as to the mechanism and enzymatic nature of the iodothyronine deiodination reaction, a detailed and systematic study of the reaction was made, and the results are summarized below.inhibitor was found in the soluble portion of the cell and was readily dialyzable. The identity of the inhibitor remains unknown, but a number of reducing substances such as ascorbate, reduced nicotinamideadenine dinucleotide, reduced nicotinamide-adenine dinucleotide phosphate, cysteine, and reduced glutathione markedly inhibited deiodination. Therefore, the inhibitor may be a reducing substance that keeps either the active site on the enzyme or the substrate in the reduced form so that deiodination cannot proceed. Such a concept presupposes that deiodination is intimately concerned with oxidation of the thyronine ring structure, probably through the formation of a quinone. Removal of B-ring iodines may actually be secondary to oxidation of the phenol group, and the natural inhibitor may interfere with this oxidative step. Experimental ProcedureAnimals and Tissue Homngenates. Holtzman strain male rats weighing 100-110 g were maintained on a Purina chow diet for at least 3 weeks prior to the experiment. The animals were sacrificed by decapitation, and 2.00-g samples of tissue were quickly removed and homogenized in a s...

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Section: Discussionmentioning

confidence: 86%

mentioning

confidence: 99%

Properties of a Rat Tissue Iodothyronine Deiodinase and Its Natural Inhibitor^*

Nakagawa¹,

Ruegamer²

1967

Biochemistry

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“…As opposed to deiodinases from rat liver homogenates (Stanbury 1960, Wynn and Gibbs 1962, Yamamoto 1964 membrane deiodination is highly active without the addition of any activators. Stimulation by Ca 2 + and Cu z + seems to be a property of the membrane system alone.…”

Section: Discussionmentioning

confidence: 96%

Demonstration of a Membrane-Linked Deiodination of Thyroid Hormones from Human Red Cell Membranes

Reinwein¹,

Ha²

1972

Horm Metab Res

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The deiodinaton of 1311-labeled thyroxine and trüodothyronine by red ceU membranes prepared from healthy persons was examined. Vnder the experimental conditions (pH 6.0, 32°C) 0.5 mg membranes deiodinated 1.6 m", moles triiodothyronine in 30 min. Iodide and a substance with an Rf of 0 in paper chromatography were the only radioactive deiodination products. The membrane system was shown to be heat stabile and dependent on an alkali labile nondialyzable factor. Iodide release is linked to membrane partieles and can be demonstrated even after lipid extraction of the ghosts. The deiodinating system is highly active without the addition of any activators and is characterized by time dependency and a pH optimum of 6.0. Stimulators of the reaction are oxygen, Ca 2 +, Cu 2 + and fructose 1,6-diphosphate. A peroxidative mechanism catalyzed by traces of hemoglobin and a non~nzymatic FMN 1ight-induced iodide release could be exeluded. The membrane-linked deiodination might play an important role in the peripheral metabolism of thyroid hormones.

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Effects of epinephrine and chemically related compounds on enzymatic deiodination of thyroxine, triiodothyronine, monoiodotyrosine and diiodotyrosine in vitro

Kobayashi¹,

Yamada²,

Shichijo³

1966

Metabolism

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Possible role of ascorbic acid as a physiological depressant of thyroxine degradation in rat liver

Cited by 3 publications

References 15 publications

Properties of a Rat Tissue Iodothyronine Deiodinase and Its Natural Inhibitor^*

Properties of a Rat Tissue Iodothyronine Deiodinase and Its Natural Inhibitor^*

Demonstration of a Membrane-Linked Deiodination of Thyroid Hormones from Human Red Cell Membranes

Effects of epinephrine and chemically related compounds on enzymatic deiodination of thyroxine, triiodothyronine, monoiodotyrosine and diiodotyrosine in vitro

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Possible role of ascorbic acid as a physiological depressant of thyroxine degradation in rat liver

Cited by 3 publications

References 15 publications

Properties of a Rat Tissue Iodothyronine Deiodinase and Its Natural Inhibitor*

Properties of a Rat Tissue Iodothyronine Deiodinase and Its Natural Inhibitor*

Demonstration of a Membrane-Linked Deiodination of Thyroid Hormones from Human Red Cell Membranes

Effects of epinephrine and chemically related compounds on enzymatic deiodination of thyroxine, triiodothyronine, monoiodotyrosine and diiodotyrosine in vitro

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About

Properties of a Rat Tissue Iodothyronine Deiodinase and Its Natural Inhibitor^*

Properties of a Rat Tissue Iodothyronine Deiodinase and Its Natural Inhibitor^*