Publications

• Study on the enzymatic 5'-deiodination of 3',5'-diiodothyronine using a radioimmunoassay for 3'-iodothyronine.

  Visser T.J., van Overmeeren-Kaptein E.

  A radioimmunoassay for 3'-iodothyronine has been developed. All iodothyronine analogues (except 3,3'-diiodothyronine) showed very litte (0.02% at most) cross-reactivity, and the assay was sensitive to 1 pg 3'-iodothyronine/tube. We have studied the 5'-deiodination of 3'-5'-diiodothyronine by rat l ... >> More

  A radioimmunoassay for 3'-iodothyronine has been developed. All iodothyronine analogues (except 3,3'-diiodothyronine) showed very litte (0.02% at most) cross-reactivity, and the assay was sensitive to 1 pg 3'-iodothyronine/tube. We have studied the 5'-deiodination of 3'-5'-diiodothyronine by rat liver microsomal fraction in the presence of dithiothreitol. Production of 3'-iodothyronine at 37 degrees C was found to be linear with time of incubation up to 30 min and with concentration of microsomal protein up to 100 microgram/ml. The reaction rate reached a limit on increasing 3',5'-diiodothyronine concentration to 10 microM. The effect of pH on 3'-iodothyronine production was found to depend on 3',5'-diiodothyronine concentration. Increasing 3,5'-diiodothyronine concentration from 0.1 to 10 microM resulted in a shjift of the pH optimum from 6-6.5 to 7.5. Similar effects on the 5'-deiodination of 3,3',5'-triiodothyronine were observed, supporting the hypothesis that these reactions are catalysed by a single enzyme (iodothyronine 5'-deiodinase). << Less

  Biochim Biophys Acta 631:246-252(1980) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Iodothyronine deiodinase structure and function: from ascidians to humans.

  Darras V.M., Van Herck S.L.

  Iodothyronine deiodinases are important mediators of thyroid hormone (TH) action. They are present in tissues throughout the body where they catalyse 3,5,3'-triiodothyronine (T(3)) production and degradation via, respectively, outer and inner ring deiodination. Three different types of iodothyroni ... >> More

  Iodothyronine deiodinases are important mediators of thyroid hormone (TH) action. They are present in tissues throughout the body where they catalyse 3,5,3'-triiodothyronine (T(3)) production and degradation via, respectively, outer and inner ring deiodination. Three different types of iodothyronine deiodinases (D1, D2 and D3) have been identified in vertebrates from fish to mammals. They share several common characteristics, including a selenocysteine residue in their catalytic centre, but show also some type-specific differences. These specific characteristics seem very well conserved for D2 and D3, while D1 shows more evolutionary diversity related to its Km, 6-n-propyl-2-thiouracil sensitivity and dependence on dithiothreitol as a cofactor in vitro. The three deiodinase types have an impact on systemic T(3) levels and they all contribute directly or indirectly to intracellular T(3) availability in different tissues. The relative contribution of each of them, however, varies amongst species, developmental stages and tissues. This is especially true for amphibians, where the impact of D1 may be minimal. D2 and D3 expression and activity respond to thyroid status in an opposite and conserved way, while the response of D1 is variable, especially in fish. Recently, a number of deiodinases have been cloned from lower chordates. Both urochordates and cephalochordates possess selenodeiodinases, although they cannot be classified in one of the three vertebrate types. In addition, the cephalochordate amphioxus also expresses a non-selenodeiodinase. Finally, deiodinase-like sequences have been identified in the genome of non-deuterostome organisms, suggesting that deiodination of externally derived THs may even be functionally relevant in a wide variety of invertebrates. << Less

  J Endocrinol 215:189-206(2012) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• Activation and inactivation of thyroid hormone by type I iodothyronine deiodinase.

  Moreno M., Berry M.J., Horst C., Thoma R., Goglia F., Harney J.W., Larsen P.R., Visser T.J.

  The prohormone thyroxine (T4) is activated by outer ring deiodination (ORD) to 3,3',5-triiodothyronine (T3) and both hormones are degraded by inner ring deiodination (IRD) to 3,3',5'-triiodothyronine (rT3) and 3,3'-diiodothyronine, respectively. Indirect evidence suggests that the type I iodothyro ... >> More

  The prohormone thyroxine (T4) is activated by outer ring deiodination (ORD) to 3,3',5-triiodothyronine (T3) and both hormones are degraded by inner ring deiodination (IRD) to 3,3',5'-triiodothyronine (rT3) and 3,3'-diiodothyronine, respectively. Indirect evidence suggests that the type I iodothyronine deiodinase (ID-I) in liver has both ORD and IRD activities, with preference for rT3 and sulfated iodothyronines as substrates. To establish this, we have compared the ORD of rT3 and IRD of T3 and T3 sulfate by homogenates of cells transfected with rat ID-I cDNA and by rat liver microsomes. In both preparations rT3 is the preferred substrate, while deiodination of T3 is markedly accelerated by its sulfation. Kinetic analysis provided similar Km and Vmax values in cell homogenates and liver microsomes. These data demonstrate unequivocally that ID-I is capable of both activating and inactivating thyroid hormone by ORD and IRD, respectively. << Less

  FEBS Lett. 344:143-146(1994) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Sequential deiodination of thyroxine to 3,3'-diiodothyronine via 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine in rat liver homogenate. The effects of fasting versus glucose feeding.

  Gavin L.A., Bui F., McMahon F., Cavalieri R.R.

  The characteristics of thyroxine (T4) deiodination to 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) and of each of the latter to 3,3'-diiodothyronine (3,3'T2) were examined in rat liver homogenate. Each of the four reactions was enzymatic in nature, demonstrating pH and temperatu ... >> More

  The characteristics of thyroxine (T4) deiodination to 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) and of each of the latter to 3,3'-diiodothyronine (3,3'T2) were examined in rat liver homogenate. Each of the four reactions was enzymatic in nature, demonstrating pH and temperature optima, and tissue and time dependence. All reactions were considerably augmented (greater than 10-fold) by the presence of a thiol agent. At pH 7.2 with 2 muM T4 as substrate, rT3 generation was 3.3 +/- 0.44 (S.E.) and T3 formation was 4.8 +/-0.57 pmol/min/100 mg of homogenate protein. Fasting for 72 h resulted in a significant inhibition of T4 deiodination, compared to that in the glucose-fed animals, in a 2% homogenate preparation. Enzyme activity for T4 to T3 was reduced by 54% (p less than 0.05) in the homogenate from the fasted rats. Fasting lowered the enzyme activity of T4 to rT3 by 56% (p less than 0.05). Although the monodeiodination of T3 to 3,3'-T2 was also significantly depressed (p less than 0.01) by fasting, rT3 deiodination to 3,3'-T2 was not. The in vitro additon of 5 mM dithioerythritol did not reverse the effect of fasting on any reaction. These results demonstrate that a 72-h fast significantly impairs the sequential deiodination of T4 in liver homogenate. The effect of fasting appears to be mediated mainly through a reduction in enzyme concentration rather than co-factor availability. << Less

  J Biol Chem 255:49-54(1980) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.