Metabolism of 3,3'-diiodothyronine and 3'-monoiodothyronine, and effect of potassium cyanide and dinitrophenol on glucuronidation of thyroxine in cultured rat hepatoma cells.

Sorimachi, Kenji; Niwa, Akira; Yasumura, Yosihiro

doi:10.1507/endocrj1954.27.631

Cited by 4 publications

(3 citation statements)

References 13 publications

(21 reference statements)

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“…The deiodinations of T 4 , rT 3 and 3′,5′‐T 2 were completely inhibited by the Dio1‐specific inhibitor PTU, which is in line with published Dio1 inhibition characteristics 5. Both 3‐T 1 and 3′‐T 1 were not substrates of Dio1 from HepG2 lysates, which is consistent with previously reported data 39–41. The remaining THs, namely T 3 , 3,3′‐T 2 and 3,5‐T 2 , were also not deiodinated by Dio1 from HepG2 lysates.…”

Section: Resultssupporting

confidence: 91%

Development of a validated liquid chromatography/tandem mass spectrometry method for the distinction of thyronine and thyronamine constitutional isomers and for the identification of new deiodinase substrates

Piehl

Heberer

Balizs

et al. 2008

Rapid Comm Mass Spectrometry

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Thyronines (THs) and thyronamines (TAMs) are two groups of endogenous iodine-containing signaling molecules whose representatives differ from each other only regarding the number and/or the position of the iodine atoms. Both groups of compounds are substrates of three deiodinase isozymes, which catalyze the sequential reductive removal of iodine from the respective precursor molecule. In this study, a novel analytical method applying liquid chromatography/tandem mass spectrometry (LC-MS/MS) was developed. This method permitted the unequivocal, simultaneous identification and quantification of all THs and TAMs in the same biological sample. Furthermore, a liquid-liquid extraction procedure permitting the concurrent isolation of all THs and TAMs from biological matrices, namely deiodinase (Dio) reaction mixtures, was established. Method validation experiments with extracted TH and TAM analytes demonstrated that the method was selective, devoid of matrix effects, sensitive, linear over a wide range of analyte concentrations and robust in terms of reproducible recoveries, process efficiencies as well as intra-assay and inter-assay stability parameters. The method was applied to study the deiodination reactions of iodinated THs catalyzed by the three deiodinase isozymes. With the HPLC protocol developed herein, sufficient chromatographic separation of all constitutional TH and TAM isomers was achieved. Accordingly, the position of each iodine atom removed from a TH substrate in a Dio-catalyzed reaction was backtracked unequivocally. While several established deiodination reactions were verified, two as yet unknown reactions, namely the phenolic ring deiodination of 3',5'-diiodothyronine (3',5'-T2) by Dio2 and the tyrosyl ring deiodination of 3-monoiodothyronine (3-T1) by Dio3, were newly identified.

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Section: Resultssupporting

confidence: 91%

Development of a validated liquid chromatography/tandem mass spectrometry method for the distinction of thyronine and thyronamine constitutional isomers and for the identification of new deiodinase substrates

Piehl

Heberer

Balizs

et al. 2008

Rapid Comm Mass Spectrometry

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“…3-T1AM further undergoes tyrosyl ring deiodination by DIO3 to produce the completely deiodinated metabolite T0AM, whereas 3′-T1AM does not undergo any further deiodination to form T0AM (Scheme ). By contrast, 3′-T1 undergoes phenolic deiodination by DIO1 to form T0, whereas 3-T1 does not undergo deiodination to form T0. − These observations clearly indicate that the decarboxylation of β-alanine side chain of the thyroid hormones changes the substrate specificity of the DIOs. Recently, Scanlan and co-workers have identified apolipoprotein B-100 (apoB-100), the protein component of several low density lipoprotein particles, to be a specific transporter ( K D = 17 nM) of 3-T1AM with a 3-T1AM/apoB-100 stoichiometry of 1:1 .…”

Section: Resultsmentioning

confidence: 91%

“…Recently, TAMs have been identified as substrates for DIOs . However, some of the THs and TAMs do not undergo deiodination by these enzymes (Scheme ), − indicating that the change in the structure and conformations of THs upon decarboxylation may alter the binding of TAMs at the enzyme active site.…”

Section: Introductionmentioning

confidence: 99%

Conformational Flexibility and Halogen Bonding in Thyroid Hormones and Their Metabolites

Mondal

Mugesh

2016

Crystal Growth & Design

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Iodothyronamines (TAMs) are endogenous thyroid hormone (TH) metabolites, which are proposed to be biosynthesized by decarboxylation of the β-alanine side chain of THs. Iodothyronine deiodinases (DIOs) mediate phenolic and tyrosyl ring deiodinations of thyroid hormones and play an important role in thyroid hormone homeostasis. These enzymes also accept iodothyronamines as substrates for deiodination, but the binding affinities of TAMs to DIOs are lower than that of THs. In this paper, we report, for the first time, the formation of halogen bonding in various iodothyronamines by using single crystal X-ray studies. We also describe the conformational changes that take place in the structures of THs and TAMs upon deiodination. Density functional theory calculations were performed to understand the halogen bonded assembly and their biological implications.

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Chemie und Biologie der Schilddrüsenhormon‐Biosynthese und ‐Wirkung

Mondal¹,

Raja²,

Schweizer

et al. 2016

Angewandte Chemie

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Schilddrüsenhormone (THs) werden von der Schilddrüse abgegeben. Sie kontrollieren Fett‐, Kohlenhydrat‐ und Proteinmetabolismus, Herzfrequenz, neuronale Entwicklung sowie kardiovaskuläre, renale und neuronale Funktionen. Die Schilddrüse produziert überwiegend l‐Thyroxin (T4), das als Prohormon fungiert. Durch 5′‐Deiodierung, katalysiert von Iodthyronin‐Deiodasen, wird aktives T3 gebildet, das an den nukleären Schilddrüsenhormon‐Rezeptor bindet. In diesem Aufsatz fassen wir sowohl die grundlegende Chemie und Biologie als auch die neuesten Erkenntnisse zur TH‐Biosynthese, zum Plasmatransport und zur Internalisierung der THs in die Zielorgane, zur Deiodierung und zu einer Vielzahl anderer Enzym‐vermittelter Stoffwechselwege zusammen. Zudem erörtern wir Schilddrüsenhormon‐Rezeptoren, verschiedene Schilddrüsen‐bedingte Krankheiten und deren Therapien.

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Metabolism of 3,3'-diiodothyronine and 3'-monoiodothyronine, and effect of potassium cyanide and dinitrophenol on glucuronidation of thyroxine in cultured rat hepatoma cells.

Abstract: Rat hepatoma cells (R117-

Cited by 4 publications

References 13 publications

Development of a validated liquid chromatography/tandem mass spectrometry method for the distinction of thyronine and thyronamine constitutional isomers and for the identification of new deiodinase substrates

Development of a validated liquid chromatography/tandem mass spectrometry method for the distinction of thyronine and thyronamine constitutional isomers and for the identification of new deiodinase substrates

Conformational Flexibility and Halogen Bonding in Thyroid Hormones and Their Metabolites

Chemie und Biologie der Schilddrüsenhormon‐Biosynthese und ‐Wirkung

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