3,5-Diiodothyronine

3,5-Diiodothyronine
Names
	IUPAC name 2-Amino-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propanoic acid
Identifiers
CAS Number	534-51-0 ;
3D model (JSmol)	Interactive image; Interactive image;
ChemSpider	110252 ;
MeSH	3,5-diiodothyronine
PubChem CID	123675;
UNII	U1Y9GN485M ;
CompTox Dashboard (EPA)	DTXSID60862141 ;
	InChI InChI=1S/C15H13I2NO4/c16-11-5-8(7-13(18)15(20)21)6-12(17)14(11)22-10-3-1-9(19)2-4-10/h1-6,13,19H,7,18H2,(H,20,21) Key: ZHSOTLOTTDYIIK-UHFFFAOYSA-N;
	SMILES C1=CC(=CC=C1O)OC2=C(C=C(C=C2I)CC(C(=O)O)N)I; C1=CC(=CC=C1O)OC2=C(C=C(C=C2I)CC(C(=O)O)N)I;
Properties
Chemical formula	C15H13I2NO4
Molar mass	525.081 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

3,5-Diiodothyronine (3,5-T₂) is an active thyroid hormone within the class of iodothyronines. It has two iodine atoms at positions 3 and 5 of its inner ring.

Biological effects

3,5-T₂ is an active thyroid hormone. It stimulates the TR-beta receptor for thyroid hormones and thus increases energy expenditure.^[1]^[2] It has agonistic (thyromimetic) effects at myocardial tissue and pituitary, which results in 3,5-T₂ suppressing TSH release.^[3]^[4] 3,5-T₂ is an allosteric regulator of the cytochrome c oxidase, the complex IV of the electron transport chain. It increases its activity by preventing the interaction of adenosine triphosphate (ATP) as an allosteric inhibitor.^[5]

Clinical significance

In nonthyroidal illness syndrome 3,5-T₂ concentrations are increased.^[6]^[7]^[8]^[9] This could explain why patients with low T3 syndrome don't benefit from substitution therapy with thyroid hormones.^[7]

References

^ Goglia F (2014). "The effects of 3,5-diiodothyronine on energy balance". Frontiers in Physiology. 5: 528. doi:10.3389/fphys.2014.00528. PMC 4292545. PMID 25628573.
^ Lombardi A, Senese R, De Matteis R, Busiello RA, Cioffi F, Goglia F, Lanni A (2015). "3,5-Diiodo-L-thyronine activates brown adipose tissue thermogenesis in hypothyroid rats". PLOS ONE. 10 (2): e0116498. Bibcode:2015PLoSO..1016498L. doi:10.1371/journal.pone.0116498. PMC 4319745. PMID 25658324.
^ Padron AS, Neto RA, Pantaleão TU, de Souza dos Santos MC, Araujo RL, de Andrade BM, da Silva Leandro M, de Castro JP, Ferreira AC, de Carvalho DP (Jun 2014). "Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues". The Journal of Endocrinology. 221 (3): 415–27. doi:10.1530/JOE-13-0502. PMC 4045230. PMID 24692290.
^ Jonas W, Lietzow J, Wohlgemuth F, Hoefig CS, Wiedmer P, Schweizer U, Köhrle J, Schürmann A (Jan 2015). "3,5-Diiodo-L-thyronine (3,5-t2) exerts thyromimetic effects on hypothalamus-pituitary-thyroid axis, body composition, and energy metabolism in male diet-induced obese mice". Endocrinology. 156 (1): 389–99. doi:10.1210/en.2014-1604. PMC 4272399. PMID 25322465.
^ Arnold S.; Goglia F.; Kadenbach B. (1998). "3,5-Diiodothyronine binds to subunit Va of cytochrome-c oxidase and abolishes the allosteric inhibition of respiration by ATP". Eur. J. Biochem. 252 (2): 325–330. doi:10.1046/j.1432-1327.1998.2520325.x. PMID 9523704.
^ Pinna G, Meinhold H, Hiedra L, Thoma R, Hoell T, Gräf KJ, Stoltenburg-Didinger G, Eravci M, Prengel H, Brödel O, Finke R, Baumgartner A (May 1997). "Elevated 3,5-diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors". The Journal of Clinical Endocrinology and Metabolism. 82 (5): 1535–42. doi:10.1210/jcem.82.5.3939. PMID 9141546.
^ ^a ^b Dietrich JW, Müller P, Schiedat F, Schlömicher M, Strauch J, Chatzitomaris A, Klein HH, Mügge A, Köhrle J, Rijntjes E, Lehmphul I (Jun 2015). "Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling". European Thyroid Journal. 4 (2): 129–37. doi:10.1159/000381543. PMC 4521060. PMID 26279999.
^ Langouche, L; Lehmphul, I; Perre, SV; Köhrle, J; Van den Berghe, G (December 2016). "Circulating 3-T1AM and 3,5-T2 in Critically Ill Patients: A Cross-Sectional Observational Study". Thyroid. 26 (12): 1674–1680. doi:10.1089/thy.2016.0214. PMID 27676423.
^ Chatzitomaris, Apostolos; Hoermann, Rudolf; Midgley, John E.; Hering, Steffen; Urban, Aline; Dietrich, Barbara; Abood, Assjana; Klein, Harald H.; Dietrich, Johannes W. (20 July 2017). "Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming". Frontiers in Endocrinology. 8: 163. doi:10.3389/fendo.2017.00163. PMC 5517413. PMID 28775711.

External links

3,5-diiodothyronine at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

[1] Goglia F (2014). "The effects of 3,5-diiodothyronine on energy balance". Frontiers in Physiology. 5: 528. doi:10.3389/fphys.2014.00528. PMC 4292545. PMID 25628573.

[2] Lombardi A, Senese R, De Matteis R, Busiello RA, Cioffi F, Goglia F, Lanni A (2015). "3,5-Diiodo-L-thyronine activates brown adipose tissue thermogenesis in hypothyroid rats". PLOS ONE. 10 (2): e0116498. Bibcode:2015PLoSO..1016498L. doi:10.1371/journal.pone.0116498. PMC 4319745. PMID 25658324.

[3] Padron AS, Neto RA, Pantaleão TU, de Souza dos Santos MC, Araujo RL, de Andrade BM, da Silva Leandro M, de Castro JP, Ferreira AC, de Carvalho DP (Jun 2014). "Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues". The Journal of Endocrinology. 221 (3): 415–27. doi:10.1530/JOE-13-0502. PMC 4045230. PMID 24692290.

[4] Jonas W, Lietzow J, Wohlgemuth F, Hoefig CS, Wiedmer P, Schweizer U, Köhrle J, Schürmann A (Jan 2015). "3,5-Diiodo-L-thyronine (3,5-t2) exerts thyromimetic effects on hypothalamus-pituitary-thyroid axis, body composition, and energy metabolism in male diet-induced obese mice". Endocrinology. 156 (1): 389–99. doi:10.1210/en.2014-1604. PMC 4272399. PMID 25322465.

[5] Arnold S.; Goglia F.; Kadenbach B. (1998). "3,5-Diiodothyronine binds to subunit Va of cytochrome-c oxidase and abolishes the allosteric inhibition of respiration by ATP". Eur. J. Biochem. 252 (2): 325–330. doi:10.1046/j.1432-1327.1998.2520325.x. PMID 9523704.

[6] Pinna G, Meinhold H, Hiedra L, Thoma R, Hoell T, Gräf KJ, Stoltenburg-Didinger G, Eravci M, Prengel H, Brödel O, Finke R, Baumgartner A (May 1997). "Elevated 3,5-diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors". The Journal of Clinical Endocrinology and Metabolism. 82 (5): 1535–42. doi:10.1210/jcem.82.5.3939. PMID 9141546.

[dietrich2015-7] Dietrich JW, Müller P, Schiedat F, Schlömicher M, Strauch J, Chatzitomaris A, Klein HH, Mügge A, Köhrle J, Rijntjes E, Lehmphul I (Jun 2015). "Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling". European Thyroid Journal. 4 (2): 129–37. doi:10.1159/000381543. PMC 4521060. PMID 26279999.

[8] Langouche, L; Lehmphul, I; Perre, SV; Köhrle, J; Van den Berghe, G (December 2016). "Circulating 3-T1AM and 3,5-T2 in Critically Ill Patients: A Cross-Sectional Observational Study". Thyroid. 26 (12): 1674–1680. doi:10.1089/thy.2016.0214. PMID 27676423.

[Chatzitomaris_2017-9] Chatzitomaris, Apostolos; Hoermann, Rudolf; Midgley, John E.; Hering, Steffen; Urban, Aline; Dietrich, Barbara; Abood, Assjana; Klein, Harald H.; Dietrich, Johannes W. (20 July 2017). "Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming". Frontiers in Endocrinology. 8: 163. doi:10.3389/fendo.2017.00163. PMC 5517413. PMID 28775711.

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