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Cited by 65Thyroid Disorders and TreatmentsEnzyme Structure and FunctionChemical Analysis and Environmental Impact

Efficient use and recycling of the micronutrient iodide in mammals

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Rokita, Steven E., Adler, Jennifer M., McTamney, Patrick M., Watson Jr., James A.·2010·Biochimie
DOI 10.1016/j.biochi.2010.02.013PMC PMC2888766
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Abstract

Daily ingestion of iodide alone is not adequate to sustain production of the thyroid hormones, tri- and tetraiodothyronine. Proper maintenance of iodide in vivo also requires its active transport into the thyroid and its salvage from mono- and diiodotyrosine that are formed in excess during hormone biosynthesis. The enzyme iodotyrosine deiodinase responsible for this salvage is unusual in its ability to catalyze a reductive dehalogenation reaction dependent on a flavin cofactor, FMN. Initial characterization of this enzyme was limited by its membrane association, difficult purification and poor stability. The deiodinase became amenable to detailed analysis only after identification and heterologous expression of its gene. Site-directed mutagenesis recently demonstrated that cysteine residues are not necessary for enzymatic activity in contrast to precedence set by other reductive dehalogenases. Truncation of the N-terminal membrane anchor of the deiodinase has provided a soluble and stable source of enzyme sufficient for crystallographic studies. The structure of an enzyme.substrate co-crystal has become invaluable for understanding the origins of substrate selectivity and the mutations causing thyroid disease in humans.

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Authors
Rokita, S. E., Adler, J. M., McTamney, P. M., & Watson Jr., J. A.
Affiliations
University of Maryland, College Park (US)
Corresponding author
Rokita, Steven E.
ORCID
Rokita, Steven E.
Venue
Biochimie
Publisher
Elsevier BV
Published
2010-09
Volume
92
Issue
9
Pages
1227-1235
ISSN
  • 0037-9042 (ISSN-L)
  • 0300-9084
DOI
10.1016/j.biochi.2010.02.013
PMC
PMC2888766
OpenAlex
W2095253816
Cited by
65
References
1
Citations by year
2026: 3 · 2025: 1 · 2024: 3 · 2022: 7 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 4 · 2017: 10 · 2016: 3 · 2015: 6 · 2014: 8 · 2013: 7 · 2012: 4
FWCI
2.78
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biochimie (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK084186, DK084186)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Chemical Analysis and Environmental Impact
Keywords
iodotyrosine deiodinase, thyroid hormone synthesis, triiodothyronine, thyroxine, reductive dehalogenase, enzyme structure, substrate specificity, cysteine residues, heterologous expression, iodide transport
MeSH terms
Animals, Humans, Iodide Peroxidase, Iodides, Thyroid Gland, Mutagenesis, Site-Directed, Micronutrients

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