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Event: 1152

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Inhibition, Iodotyrosine deiodinase (IYD)

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Inhibition, Iodotyrosine deiodinase (IYD)
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Cell term
eukaryotic cell

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
catalytic activity iodotyrosine deiodinase 1 (human) decreased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
IYD inhib alters metamorphosis MolecularInitiatingEvent Jonathan Haselman (send email) Under Development: Contributions and Comments Welcome

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
African clawed frog Xenopus laevis NCBI
Amphibia Amphibia Moderate NCBI
mammals mammals Moderate NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Taxonomic: According to the evaluation of the empirical taxonomic domain of applicability (tDOA) of an adverse outcome pathway network for thyroid hormone system disruption (THSD) by Haigis et al., 2023, the level of confidence for a linkage between IYD inhibition and reduced thyroid hormone (TH) levels was considered moderate for mammals and amphibians (Gaupale et al., 2009, Gnidehou et al., 2004, Green, 1971, Meinhold and Buchholz, 1983, Olker et al., 2018, 2021, 2022, Phatarphekar et al., 2014, Shimizu et al., 2013). This was supported by structural protein conservation analysis by Lalone et al., 2018 and Haigis et al., 2023. Structural protein conservation of mammalian, amphibian, fish, reptilian and avian IYD was found compared to the human (Homo sapiens) protein target using the U.S. Environmental Protection Agency’s Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS v6.0; seqapass.epa.gov/seqapass/) tool, while acknowledging the potential existence of interspecies differences in conservation. No empirical evidence linking IYD inhibition to THSD was found for fish, reptiles and birds.

References

List of the literature that was cited for this KE description. More help

Gaupale, T. C., Mathi, A. A., Ravikumar, A., and Bhargava, S. Y. (2009). Localization and enzyme activity of iodotyrosine dehalogenase 1 during metamorphosis of frog Microhyla ornata. Ann. NY Acad. Sci. 1163, 402–406.

Gnidehou, S., Caillou, B., Talbot, M., Ohayon, R., Kaniewski, J., Noël-Hudson, M., Morand, S., Agnangji, D., Sezan, A., Courtin, F., et al. (2004). Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site. FASEB J. 18, 1574–1576.

Green, W. L. (1971). Effects of 3-nitro- L-tyrosine on thyroid function in the rat: An experimental model for the dehalogenase defect. J. Clin. Invest. 50, 2474–2484.

Haigis A-C., Vergauwen L., LaLone C.A., Villeneuve D.L., O'Brien J.M., Knapen D. (2023). Cross-species applicability of an adverse outcome pathway network for thyroid hormone system disruption. Toxicol Sci. 195, 1-27.

Lalone, C. A., Villeneuve, D. L., Doering, J. A., Blackwell, B. R., Transue, T. R., Simmons, C. W., Swintek, J., Degitz, S. J., Williams, A. J., and Ankley, G. T. (2018). Evidence for cross species extrapolation of mammalian-based high-throughput screening assay results. Environ. Sci. Technol. 52, 13960–13971

Meinhold, H., and Buchholz, R. (1983). Effects of iodotyrosine deiodinase inhibition on serum concentrations and turnover of diiodotyrosine (DIT) and thyroxine (T4) in the rat. Acta Endocrinol. 103, 521–527.

Olker, J. H., Haselman, J. T., Kosian, P. A., Donnay, K. G., Korte, J. J., Blanksma, C., Hornung, M. W., and Degitz, S. J. (2018). Evaluating iodide recycling inhibition as a novel molecular initiating event for thyroid axis disruption in amphibians. Toxicol. Sci. 166, 318–331.

Olker, J. H., Korte, J. J., Denny, J. S., Haselman, J. T., Hartig, P. C., Cardon, M. C., Hornung, M. W., and Degitz, S. J. (2021). In vitro screening for chemical inhibition of the iodide recycling enzyme, iodotyrosine deiodinase. Toxicol. In Vitro 71, 105073.

Olker, J. H., Korte, J. J., Haselman, J. T., Hornung, M. W., and Degitz, S.J. (2022). Cross-species comparison of chemical inhibition of human and Xenopus iodotyrosine deiodinase. Aquat. Toxicol. 249, 106227.

Phatarphekar, A., Buss, J. M., and Rokita, S. E. (2014). Iodotyrosine deiodinase: A unique flavoprotein present in organisms of diverse phyla. Mol. Biosyst. 10, 86–92.

Shimizu, R., Yamaguchi, M., Uramaru, N., Kuroki, H., Ohta, S., Kitamura, S., and Sugihara, K. (2013). Structure-activity relationships of 44 halogenated compounds for iodotyrosine deiodinase-inhibitory activity. Toxicology 314, 22–29.