Ji, Cindy Xinyu;
Zonias, Danae;
Djumaeva, Nafisa;
Cheng, Ranchu;
Salim, Kawther;
Alikhani, Pouya;
Oyelade, Tope;
... Mani, Ali R; + view all
(2024)
Identification and determination of the urinary metabolite of iodotyrosine in vivo.
Biochemical and Biophysical Research Communications
, Article 150854. 10.1016/j.bbrc.2024.150854.
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Abstract
Background: Congenital hypothyroidism screening traditionally relies on detecting elevated thyroid-stimulating hormone levels, yet this approach may not detect a specific type of congenital hypothyroidism caused by iodotyrosine dehalogenase-1 (Dehal1) deficiency. The deficiency of this enzyme prevents the deiodination of mono-iodotyrosine (MIT) and di-iodotyrosine (DIT) in the process of iodine recycling. This underscores the potential use of iodotyrosine or its metabolites as non-invasive urinary biomarkers for early diagnosis of congenital hypothyroidism. However, the urinary metabolites of MIT/DIT have not yet been discovered. Thus, this study aimed to identify the urinary metabolites of iodotyrosine in experimental models. Method: Gas chromatography mass spectrometry was used to identify the urinary metabolites of iodotyrosine following intraperitoneal injection of MIT in rats. An isotope dilution mass spectrometric assay was developed for assessment of identified metabolites. Urine samples from Dehal1 knockout mice were used to confirm the results. Results: We identified novel iodotyrosine metabolites, 3-iodo-4-hydroxyphenylacetic acid (IHPA), and 3,5-diiodo4-hydroxyphenylacetic acid (Di-IHPA) as the primary urinary metabolites of MIT and DIT respectively. The concentrations of urinary IHPA and Di-IHPA were significantly higher in Dehal1 knockout mice. Conclusion: Our findings suggest that IHPA is detected in larger quantities and may hold more clinical significance than previously identified biomarkers like MIT and DIT, making it a promising candidate for diagnosing congenital hypothyroidism or other conditions associated with iodine recycling inhibition.
| Type: | Article |
|---|---|
| Title: | Identification and determination of the urinary metabolite of iodotyrosine in vivo |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.bbrc.2024.150854 |
| Publisher version: | http://dx.doi.org/10.1016/j.bbrc.2024.150854 |
| Language: | English |
| Additional information: | © 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/bync/4.0/). |
| Keywords: | Iodotyrosine deiodinase, Iodotyrosine dehalogenase, Metabolites, Urine, Mass spectrometry |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10198894 |
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