MiMeDB: Showing metabocard for Thyroxine (MMDBc0000337)

Record Information

Version

1.0

Status

Detected and Quantified

Creation Date

2020-12-10 18:35:39 UTC

Update Date

2024-10-11 02:18:49 UTC

Metabolite ID

MMDBc0000337

Metabolite Identification

Common Name

Thyroxine

Description

Thyroxine (3,5,3‚Ä≤,5‚Ä≤-tetraiodothyronine) or T4 is one of two major hormones derived from the thyroid gland, the other being triiodothyronine (T3). The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half-life than T3. In humans, the ratio of T4 to T3 released into the blood is approximately 14:1. T4 is converted to the active T3 (three to four times more potent than T4) within cells by enzymes known as deiodinases (5‚Ä≤-iodinase). Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Iodine is critical to the synthesis of thyroxine and other thyroid hormones. Through a reaction with the enzyme thyroperoxidase, iodine is covalently bound to tyrosine residues found in the thyroglobulin protein, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). Linking two moieties of DIT produces thyroxine. Combining one molecule of MIT and one molecule of DIT produces triiodothyronine. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Iodide is actively absorbed from the bloodstream and concentrated in the thyroid follicles where thyroxine is produced. If there is a deficiency of dietary iodine, the thyroid enlarges in an attempt to trap more iodine, resulting in a condition called goitre. More specifically, the lack of thyroid hormones will lead to decreased negative feedback on the pituitary gland, leading to increased production of thyroid-stimulating hormone, which causes the thyroid to enlarge, leading to goitre. Thyroxine can be peripherally de-iodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid hormones function via a well-studied set of nuclear receptors, termed the thyroid hormone receptors. They act on nearly every cell in the body. In particular, thyroid hormones act to increase the basal metabolic rate, affect protein synthesis, help regulate long bone growth (synergy with growth hormone) and neural maturation, and increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness. The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis. Levothyroxine, a manufactured form of thyroxine, was the most prescribed medication in the United States with more than 114 million prescriptions.

Structure

MOL SDF PDB SMILES InChI

Synonyms

Not Available

Molecular Formula

C₁₅H₁₁I₄NO₄

Average Mass

776.87

Monoisotopic Mass

776.686681525

IUPAC Name

Not Available

Traditional Name

Not Available

CAS Registry Number

Not Available

SMILES

Not Available

InChI Identifier

InChI=1S/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)/t12-/m0/s1

InChI Key

XUIIKFGFIJCVMT-LBPRGKRZSA-N

Chemical Taxonomy

Functional Ontology

Not Available

Physical Properties

State

Expected Solid

Predicted Properties

Not Available

Spectra

Not Available

Biological Properties

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biospecimen Locations

Adipose Tissue
Blood
Feces
Fibroblasts
Intestine
Neuron
Ovary
Placenta
Platelet
Prostate
Saliva
Skeletal Muscle
Spleen
Testis
Thyroid Gland
Urine

Tissue Locations

Adipose Tissue
Fibroblasts
Intestine
Neuron
Ovary
Placenta
Platelet
Prostate
Skeletal Muscle
Spleen
Testis
Thyroid Gland

Associated OMIM IDs

114500 (Colorectal cancer)
610247 (Eosinophilic esophagitis)

Human Proteins and Enzymes

Protein ID	Protein Name	Protein Type	Uniprot ID	Species
MMDBp0191946	Thyroid peroxidase	Unknown	P07202	Homo sapiens
MMDBp0192113	Solute carrier organic anion transporter family member 1C1	Transporter	Q9NYB5	Homo sapiens
MMDBp0192115	Solute carrier organic anion transporter family member 1B1	Transporter	Q9Y6L6	Homo sapiens
MMDBp0192670	Type I iodothyronine deiodinase	Enzyme	P49895	Homo sapiens
MMDBp0192671	Type II iodothyronine deiodinase	Enzyme	Q92813	Homo sapiens
MMDBp0193289	Transthyretin	Enzyme	P02766	Homo sapiens
MMDBp0193712	Thyroxine-binding globulin	Enzyme	P05543	Homo sapiens
MMDBp0193808	4F2 cell-surface antigen heavy chain	Unknown	P08195	Homo sapiens
MMDBp0196040	Type III iodothyronine deiodinase	Enzyme	P55073	Homo sapiens
MMDBp0196982	Sulfotransferase 6B1	Unknown	Q6IMI4

Human Pathways

Pathways

Name	SMPDB/PathBank

Metabolic Reactions

Reactions

Reaction ID	Precursor	Product	Enzyme	Data Source	Reference
MMDBr0001498	3,5-Diiodo-L-tyrosine	2-Aminoacrylic acid	thyroid peroxidase	VMH	2997169 3153466 3475693
MMDBr0003910	Thyroxine	3,5,3,5-Tetraiodo-L-Thyronine-Beta-D-Glucuronoside	UDP glucuronosyltransferase 1 family, polypeptide A8	VMH	7263841 8405382
MMDBr0003911	Thyroxine	3,5,3,5-Tetraiodo-L-Thyronine-Beta-D-Glucuronoside	UDP glucuronosyltransferase 1 family, polypeptide A10	VMH	7263841 8405382
MMDBr0010436	Iodide	Thyroxine	deiodinase, iodothyronine, type I	VMH; KEGG	30371894
MMDBr0010437	Iodide	Thyroxine	deiodinase, iodothyronine, type I	VMH	30371894

Health Effects and Bioactivity

Health Outcome/Bioactivity	Metabolite Response/Effect	Evidence Type	Host and Biospecimen	Data Source	Reference
Anorexia nervosa	Slight Decrease	Association	Human Blood	HMDB	10197568
Hypothyroidism		Association	Human Blood	HMDB	9849813
Proteinuria		Association	Human Urine	HMDB	18238748

Microbial Sources

Superkingdom/Kingdom	Phylum	Total species	Hosts and Body Sites	Microbial Links
Bacteria	Firmicutes	1	Human stool; Human ; Human urine; Human feces	Indirect association between microbiota composition and metabolites measured in host biospecimen

Exposure Sources

Source Type	Activity	Data Source	Reference
Drugs	Not Available	U.S. Environmental Protection Agency	CompTox
Drugs	Antimicrobial	U.S. Environmental Protection Agency	CompTox
Cosmetics	Not Available	U.S. Environmental Protection Agency	CompTox
Domestics	Not Available	U.S. Environmental Protection Agency	CompTox
Domestics	Not Available	U.S. Environmental Protection Agency	CompTox

Host Biospecimen and Location

Host and Biospecimen	Status	Mean	Std	Min	Max	Units	Age	Sex	Health Condition	Data Source	Reference
Human Feces	Detected but not Quantified									HMDB
Human Blood	Detected and Quantified	0.0953				uM	Adult (>18 years old)	Female	Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency	HMDB	7951484
Human Blood	Detected and Quantified	0.000011	0.0000016			uM	Adolescent (13-18 years old)	Female	Anorexia nervosa	HMDB	10197568
Human Blood	Detected and Quantified	0.0579				uM	Newborn (0-30 days old)	Male	Diabetes Mellitus, Congenital Insulin-dependent, With Fatal Secretory Diarrhea; Immunodeficiency, Polyendocrinopathy, and Enteropathy, X-linked, Formerly	HMDB	11295725
Human Blood	Detected and Quantified	0.0000185	0.0000052			uM	Adult (>18 years old)	Both	Hypothyroidism	HMDB	9849813
Human Blood	Detected and Quantified			0.0180	0.0206	uM	Children (1-13 years old)	Male	Hypothyroidism, congenital, nongoitrous, 2	HMDB	7234795
Human Blood	Detected and Quantified			23	55.2	uM	Children (1-13 years old)	Both	Hypothyroidism, congenital, nongoitrous, 2	HMDB	17468187
Human Blood	Detected and Quantified	0.0747				uM	Infant (0-1 year old)	Female	Leptin Deficiency or Dysfunction	HMDB	10486419
Human Blood	Detected and Quantified			0.0260	0.164	uM	Infant (0-1 year old)	Male	Pendred Syndrome	HMDB	1389454
Human Blood	Detected and Quantified			0.0540	0.112	uM	Newborn (0-30 days old)	Both	Pendred Syndrome	HMDB	1389454
Human Blood	Detected and Quantified	0.00000219				uM	Adult (>18 years old)	Male	Pituitary Hormone Deficiency, Combined, 1	HMDB	28356564
Human Blood	Detected and Quantified	0.00000557				uM	Children (1-13 years old)	Male	Pituitary Hormone Deficiency, Combined, 1	HMDB	28356564
Human Blood	Detected and Quantified	0.000009				uM	Children (1-13 years old)	Female	Pituitary Hormone Deficiency, Combined, 1	HMDB	25161449
Human Blood	Detected and Quantified	<0.0100				uM	Children (1-13 years old)	Male	Pituitary Hormone Deficiency, Combined, 1	HMDB	28356564
Human Blood	Detected and Quantified	0.000009				uM	Adult (>18 years old)	Female	Proprotein Convertase 1/3 Deficiency	HMDB	7477119
Human Urine	Detected and Quantified	0.0015	0.00154			umol/mmol creatinine	Adult (>18 years old)	Both	Proteinuria	HMDB	18238748
Human Saliva	Detected and Quantified			0.0	1.0	uM	Adult (>18 years old)	Both	Normal	HMDB	15179829
Human Blood	Detected and Quantified			0.000009	0.00002	uM	Adult (>18 years old)	Not Specified	Normal	HMDB	7477119
Human Blood	Detected and Quantified			0.00001	0.000023	uM	Children (1-13 years old)	Not Specified	Normal	HMDB	28356564
Human Blood	Detected and Quantified			0.000012	0.000025	uM	Adult (>18 years old)	Not Specified	Normal	HMDB	28356564
Human Blood	Detected and Quantified	0.0000144	0.0000036			uM	Adolescent (13-18 years old)	Female	Normal	HMDB	10197568
Human Blood	Detected and Quantified	0.000016		0.0000064	0.000064	uM	Adult (>18 years old)	Both	Normal	HMDB	17936741
Human Urine	Detected and Quantified	0.00032	0.00015			umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	18238748
Human Blood	Detected and Quantified			0.0515	0.142	uM	Infant (0-1 year old)	Not Specified	Normal	HMDB	10486419
Human Blood	Detected and Quantified			0.0579	0.148	uM	Children (1-13 years old)	Not Specified	Normal	HMDB	7234795
Human Blood	Detected and Quantified			0.0600	0.150	uM	Children (1-13 years old)	Not Specified	Normal	HMDB	28356564
Human Blood	Detected and Quantified			0.0700	0.175	uM	Infant (0-1 year old)	Both	Normal	HMDB	1389454
Human Blood	Detected and Quantified			0.105	0.215	uM	Newborn (0-30 days old)	Both	Normal	HMDB	1389454
Human Blood	Detected and Quantified	0.13	0.0061			uM	Children (1-13 years old)	Both	Normal	HMDB	10731506
Human Blood	Detected and Quantified			60	160	uM	Children (1-13 years old)	Not Specified	Normal	HMDB	17468187
Human Blood	Detected and Quantified			0.000009	0.000023	uM		Both	Normal	HMDB	Geigy Scientific Tables, 8th Rev edition, pp. 130. Edited by C. Lentner, West Cadwell, N.J.: Medical education Div., Ciba-Geigy Corp. Basel, Switzerland c1981-1992.
Human Blood	Detected and Quantified	0.00002		0.00001	0.00003	uM	Adult (>18 years old)	Both	Normal	HMDB	Wu AHB. Tietz clinical guide to laboratory tests. 4th ed. St. Louis: Saunders/Elsevier, 2006.
Human Blood	Detected and Quantified			0.000010	0.000023	uM	Adult (>18 years old)	Female	Normal	HMDB	K&S Clinical Diagnostics (http://www.ksdiagnostics.com)
Human Blood	Detected and Quantified			0.000010	0.000023	uM	Adult (>18 years old)	Male	Normal	HMDB	K&S Clinical Diagnostics (http://www.ksdiagnostics.com)
Human Blood	Detected and Quantified			0.000010	0.000023	uM	Adult (>18 years old)	Both	Normal	HMDB	K&S Clinical Diagnostics (http://www.ksdiagnostics.com)
Human Blood	Detected and Quantified			0.0399	0.162	uM	Adult (>18 years old)	Both	Normal	HMDB	K&S Clinical Diagnostics (http://www.ksdiagnostics.com)
Human Adipose tissue	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Fibroblasts	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Intestine	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Neuron	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Ovary	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Placenta	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Platelet	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Prostate	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Skeletal muscle	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Spleen	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Testis	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Thyroid gland	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597

External Links

HMDB ID

Not Available

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

Not Available

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Not Available

METLIN ID

Not Available

PubChem Compound

Not Available

PDB ID

Not Available

ChEBI ID

Not Available

Food Biomarker Ontology

Not Available

References

Synthesis Reference

Not Available

General References

Marks P, Anderson J, Vincent R: Aldosterone in myxoedema. Lancet. 1978 Dec 16;2(8103):1277-8. doi: 10.1016/s0140-6736(78)92040-8. [PubMed:82781 ]
Etling N, Gehin-Fouque F, Vielh JP, Gautray JP: The iodine content of amniotic fluid and placental transfer of iodinated drugs. Obstet Gynecol. 1979 Mar;53(3):376-80. [PubMed:424113 ]
Bode HH, Vanjonack WJ, Crawford JD: Mitigation of cretinism by breast-feeding. Pediatrics. 1978 Jul;62(1):13-6. [PubMed:683777 ]
Kurz W, Wittlinger G, Litmanovitch YI, Romanoff H, Pfeifer Y, Tal E, Sulman FG: Effect of manual lymph drainage massage on urinary excretion of neurohormones and minerals in chronic lymphedema. Angiology. 1978 Oct;29(10):764-72. doi: 10.1177/000331977802901007. [PubMed:717839 ]
Sutherland RL, Simpson-Morgan MW: The thyroxine-binding properties of serum proteins. A competitive binding technique employing sephadex G-25. J Endocrinol. 1975 Jun;65(3):319-32. doi: 10.1677/joe.0.0650319. [PubMed:807668 ]
Kahan IL, Varsanyi-Nagy M, Toth M, Nadrai A: The possible role of tear fluid thyroxine in keratoconus development. Exp Eye Res. 1990 Apr;50(4):339-43. doi: 10.1016/0014-4835(90)90134-g. [PubMed:2338121 ]
Randolph VS: Four clinical chemistry analyses for pediatric patients: glycosylated hemoglobin, free bilirubin, sweat electrolytes, neonatal thyroxine. Am J Med Technol. 1982 Jan;48(1):15-22. [PubMed:7041647 ]
Hays MT, McGuire RA, Hoogeveen JT, Diezeraad KN: Measurement method for radioactive thyroxine, triiodothyronine, iodide, and iodoprotein in samples with low activity. J Nucl Med. 1980 Mar;21(3):225-32. [PubMed:7365515 ]
Gil-Loyzaga P, Remezal M, Mollicone R, Ibanez A, Oriol R: H and B human blood-group antigen expression in cochlear hair cells is modulated by thyroxine. Cell Tissue Res. 1994 May;276(2):239-43. doi: 10.1007/BF00306109. [PubMed:8020061 ]
Braley-Mullen H, Sharp GC: A thyroxine-containing thyroglobulin peptide induces both lymphocytic and granulomatous forms of experimental autoimmune thyroiditis. J Autoimmun. 1997 Dec;10(6):531-40. doi: 10.1006/jaut.1997.0160. [PubMed:9451592 ]
Zenovko EI, Pavlov BA, Koreshkov GG, Gudukina GN, Sonkina EG: [Hypothalamo-pituitary-thyroid system in patients with rheumatoid arthritis]. Ter Arkh. 1998;70(1):49-52. [PubMed:9532653 ]
Jagannathan NR, Tandon N, Raghunathan P, Kochupillai N: Reversal of abnormalities of myelination by thyroxine therapy in congenital hypothyroidism: localized in vivo proton magnetic resonance spectroscopy (MRS) study. Brain Res Dev Brain Res. 1998 Aug 8;109(2):179-86. doi: 10.1016/s0165-3806(98)00081-9. [PubMed:9729372 ]
Raghu P, Reddy GB, Sivakumar B: Inhibition of transthyretin amyloid fibril formation by 2,4-dinitrophenol through tetramer stabilization. Arch Biochem Biophys. 2002 Apr 1;400(1):43-7. doi: 10.1006/abbi.2002.2779. [PubMed:11913969 ]
van Wassenaer AG, Stulp MR, Valianpour F, Tamminga P, Ris Stalpers C, de Randamie JS, van Beusekom C, de Vijlder JJ: The quantity of thyroid hormone in human milk is too low to influence plasma thyroid hormone levels in the very preterm infant. Clin Endocrinol (Oxf). 2002 May;56(5):621-7. doi: 10.1046/j.1365-2265.2002.01526.x. [PubMed:12030913 ]
Benvenga S, Alesci S, Trimarchi F: High-density lipoprotein-facilitated entry of thyroid hormones into cells: a mechanism different from the low-density lipoprotein-facilitated entry. Thyroid. 2002 Jul;12(7):547-56. doi: 10.1089/105072502320288384. [PubMed:12193297 ]
Gil'miiarova FN, Pervova IuV, Radomskaia VM, Gergel' NI, Tarasova SV: [Levels of unified metabolites and thyroid hormones in blood and oral fluid of children with minimal brain dysfunction]. Biomed Khim. 2004 Mar-Apr;50(2):204-10. [PubMed:15179829 ]
Escobar-Morreale HF, Botella-Carretero JI, Gomez-Bueno M, Galan JM, Barrios V, Sancho J: Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone. Ann Intern Med. 2005 Mar 15;142(6):412-24. doi: 10.7326/0003-4819-142-6-200503150-00007. [PubMed:15767619 ]
Hausman GJ, Wright JT, Latimer A, Watson R, Martin RJ: The influence of human growth hormone (GH) and thyroxine (T4) on the differentiation of adipose tissue in the fetus. Obes Res. 1993 Sep;1(5):345-56. doi: 10.1002/j.1550-8528.1993.tb00012.x. [PubMed:16350585 ]
Hekimsoy Z, Oktem IK: Serum creatine kinase levels in overt and subclinical hypothyroidism. Endocr Res. 2005;31(3):171-5. doi: 10.1080/07435800500371706. [PubMed:16392619 ]
Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [PubMed:19212411 ]

Showing metabocard for Thyroxine (MMDBc0000337)

MOL for #<Metabolite:0x00007f53ba190e78>

3D MOL for #<Metabolite:0x00007f53ba190e78>

3D SDF for #<Metabolite:0x00007f53ba190e78>

3D-SDF for #<Metabolite:0x00007f53ba190e78>

PDB for #<Metabolite:0x00007f53ba190e78>

3D PDB for #<Metabolite:0x00007f53ba190e78>

SMILES for #<Metabolite:0x00007f53ba190e78>

INCHI for #<Metabolite:0x00007f53ba190e78>

Structure for #<Metabolite:0x00007f53ba190e78>

3D Structure for #<Metabolite:0x00007f53ba190e78>