Biosynthesis of 3-Iodothyronamine From T4 in Murine Intestinal Tissue

Endocrinology
Carolin S HoefigJosef Köhrle

Abstract

The endogenous metabolite 3-iodothyronamine (3-T1AM) induces strong hypothermia and bradycardia at pharmacological doses. Although its biosynthesis from thyroid hormone precursors appears likely, the sequence and sites of reactions are still controversial: studies in T4-substituted thyroid cancer patients lacking functional thyroid tissue suggested extrathyroidal 3-T1AM production, whereas studies using labeled T4 in mice indicated intrathyroidal formation. However, because the patients received T4 orally, whereas the mice were injected ip, we hypothesized that 3-T1AM synthesis requires the intestinal passage of T4. Using the everted gut sac model in combination with mass spectrometry, we demonstrate 3-T1AM production from T4 in mouse intestine via several deiodination and decarboxylation steps. Gene expression analysis confirmed the expression of all 3 deiodinases as well as ornithine decarboxylase (ODC) in intestine. Subsequent experiments employing purified human ODC revealed that this enzyme can in fact mediate decarboxylation of 3,5-T2 and T4 to the respective thyronamines (TAMs), demonstrating that the intestine expresses the entire molecular machinery required for 3-T1AM biosynthesis. Interestingly, TAM production was st...Continue Reading

References

Jul 1, 1974·Journal of Theoretical Biology·M B Dratman
May 1, 1994·European Journal of Biochemistry·E SandmeierP Christen
Mar 20, 2002·Methods in Enzymology·Josef Köhrle
May 18, 2004·Nature Medicine·Thomas S ScanlanDavid K Grandy
Feb 8, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Grazia ChielliniRiccardo Zucchi
Oct 4, 2007·Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology·L J BraulkeG Heldmaier
Mar 15, 2008·Endocrinology·S PiehlJ Köhrle
Mar 11, 2009·The Journal of Endocrinology·Lars P KlieverikAndries Kalsbeek
Jan 7, 2010·Endocrine Reviews·Sheue-Yann ChengPaul J Davis
Apr 7, 2010·Proceedings of the National Academy of Sciences of the United States of America·J H Duncan BassettGraham R Williams
Jul 14, 2010·Molecular BioSystems·Alexandra G Ianculescu, Thomas S Scanlan
Aug 27, 2010·Endocrinology·Alessandro SabaRiccardo Zucchi
Oct 1, 2010·Endocrine Reviews·S PiehlJ Köhrle
Apr 23, 2011·Journal of Molecular Endocrinology·Patrizia AgrettiMassimo Tonacchera
Nov 9, 2011·Molecular and Cellular Endocrinology·Carolin S HoefigJosef Köhrle
Jan 11, 2012·Biochimica Et Biophysica Acta·Catherine L PassarielloClaudio Stefanelli
Feb 9, 2012·The Journal of Pharmacy and Pharmacology·Mohd Aftab AlamAbdullah M Al-Mohizea
Sep 5, 2012·The Journal of Clinical Investigation·Gregory A Brent
May 11, 2013·American Journal of Physiology. Gastrointestinal and Liver Physiology·Tilo WuenschHannelore Daniel

❮ Previous
Next ❯

Citations

Dec 5, 2015·Frontiers in Endocrinology·Rudolf HoermannJohannes W Dietrich
Apr 27, 2016·Heart Failure Reviews·Alice AccorroniRiccardo Zucchi
May 27, 2016·Angewandte Chemie·Santanu MondalGovindasamy Mugesh
May 4, 2016·Expert Review of Clinical Pharmacology·Jacqueline Jonklaas
Aug 20, 2016·Organic & Biomolecular Chemistry·Santanu Mondal, Govindasamy Mugesh
Sep 22, 2016·Thyroid : Official Journal of the American Thyroid Association·Carolin Stephanie HoefigJosef Köhrle
Sep 28, 2016·Thyroid : Official Journal of the American Thyroid Association·Lies LangoucheGreet Van den Berghe
Nov 7, 2016·European Journal of Pharmacology·Annunziatina LaurinoLaura Raimondi
Jan 23, 2017·Molecular and Cellular Endocrinology·Anne H van der SpekAnita Boelen
Jun 4, 2017·The Journal of Endocrinology·Stefan GroenewegW Edward Visser
Nov 2, 2018·The Journal of Clinical Endocrinology and Metabolism·Jeppe Lerche la CourJens Faber
Jan 17, 2019·Endocrine Reviews·Josef Köhrle, Heike Biebermann
Jun 27, 2018·Pharmacological Reviews·Raul R GainetdinovMark D Berry
Mar 19, 2020·International Journal of Molecular Sciences·Grazia RutiglianoGrazia Chiellini
Oct 30, 2016·Thyroid : Official Journal of the American Thyroid Association·Nancy SchanzeJosef Köhrle
May 26, 2018·Expert Opinion on Therapeutic Targets·Michael D SchwartzRaul R Gainetdinov
Jun 18, 2017·Frontiers in Endocrinology·Hartmut H Glossmann, Oliver M D Lutz
Oct 9, 2018·Reviews in Endocrine & Metabolic Disorders·Camilla ViriliMarco Centanni
Aug 4, 2018·Frontiers in Endocrinology·Ruy A Louzada, Denise P Carvalho
Jul 31, 2019·Endocrine·Rosalba SeneseAntonia Lanni
Mar 3, 2020·Hormone Molecular Biology and Clinical Investigation·Ginevra SacripantiSandra Ghelardoni
Jun 14, 2020·International Journal of Molecular Sciences·Marco GiammancoItalia Di Liegro
Sep 29, 2020·Journal of Biomedical Science·Lesha Pretorius, Carine Smith
Jan 11, 2016·Acta Physiologica·D GnocchiP Parini
Jul 22, 2019·Endocrine·Riccardo ZucchiFederica Saponaro
Dec 15, 2019·Cellular and Molecular Neurobiology·Katlynn Bugda GwiltGregory M Miller
Feb 20, 2020·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·Klaudia BrixMaren Rehders
May 26, 2020·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·Georg HomuthJosef Köhrle
Nov 8, 2019·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·Heike Biebermann, Gunnar Kleinau
Jan 28, 2021·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Zhong-Min LiMeri De Angelis
Jan 23, 2021·Neurobiology of Disease·Francesca TozziNicola Origlia
Apr 8, 2020·European Thyroid Journal·Sogol GachkarJens Mittag
Jul 2, 2019·European Thyroid Journal·Josef Köhrle

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bradyarrhythmias

Bradyarrhythmias are slow heart rates. Symptoms may include syncope, dizziness, fatigure, shortness of breath, and chest pains. Find the latest research on bradyarrhythmias here.