T3DB: 18-Hydroxycorticosterone

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (1)XML

Targets (1)

Record Information

Version

2.0

Creation Date

2014-08-29 06:14:49 UTC

Update Date

2018-03-21 17:46:14 UTC

Accession Number

T3D4284

Identification

Common Name

18-Hydroxycorticosterone

Class

Small Molecule

Description

18-Hydroxycorticosterone is a corticosteroid and a derivative of corticosterone. If it is present in sufficiently high concentrations, it can lead to serious electrolyte imbalances (an electrolyte toxin). 18-Hydroxycorticosterone serves as an intermediate in the synthesis of aldosterone by the enzyme aldosterone synthase in the zona glomerulosa. Chronically high levels of 18-hydroxycorticosterone are associated with at least three inborn errors of metabolism including adrenal hyperplasia type V, corticosterone methyl oxidase I deficiency, and corticosterone methyl oxidase II deficiency. Each of these conditions is characterized by excessive amounts of sodium being released in the urine (salt wasting), along with insufficient release of potassium in the urine, usually beginning in the first few weeks of life. This imbalance leads to low levels of sodium and high levels of potassium in the blood (hyponatremia and hyperkalemia, respectively). Individuals with corticosterone methyloxidase deficiency can also have high levels of acid in the blood (metabolic acidosis). Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). The hyponatremia, hyperkalemia, and metabolic acidosis associated with corticosterone methyloxidase deficiency can cause nausea, vomiting, dehydration, low blood pressure, extreme tiredness (fatigue), and muscle weakness.

Compound Type

Animal Toxin
Ester
Food Toxin
Metabolite
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
11b,18,21-Trihydroxy-pregn-4-ene-3,20-dione

Chemical Formula

C₂₁H₃₀O₅

Average Molecular Mass

362.460 g/mol

Monoisotopic Mass

362.209 g/mol

CAS Registry Number

561-65-9

IUPAC Name

(1S,2R,10S,11S,14S,15R,17S)-17-hydroxy-14-(2-hydroxyacetyl)-15-(hydroxymethyl)-2-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one

Traditional Name

(1S,2R,10S,11S,14S,15R,17S)-17-hydroxy-14-(2-hydroxyacetyl)-15-(hydroxymethyl)-2-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one

SMILES

[H][C@@]1(CC[C@@]2([H])[C@]3([H])CCC4=CC(=O)CC[C@]4(C)[C@@]3([H])[C@@]([H])(O)C[C@]12CO)C(=O)CO

InChI Identifier

InChI=1S/C21H30O5/c1-20-7-6-13(24)8-12(20)2-3-14-15-4-5-16(18(26)10-22)21(15,11-23)9-17(25)19(14)20/h8,14-17,19,22-23,25H,2-7,9-11H2,1H3/t14-,15-,16+,17-,19+,20-,21+/m0/s1

InChI Key

InChIKey=HFSXHZZDNDGLQN-ZVIOFETBSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as 21-hydroxysteroids. These are steroids carrying a hydroxyl group at the 21-position of the steroid backbone.

Kingdom

Organic compounds

Super Class

Lipids and lipid-like molecules

Class

Steroids and steroid derivatives

Sub Class

Hydroxysteroids

Direct Parent

21-hydroxysteroids

Alternative Parents

Substituents

Progestogin-skeleton
21-hydroxysteroid
Pregnane-skeleton
20-oxosteroid
18-hydroxysteroid
3-oxo-delta-4-steroid
3-oxosteroid
11-hydroxysteroid
11-beta-hydroxysteroid
Oxosteroid
Delta-4-steroid
Cyclohexenone
Alpha-hydroxy ketone
Cyclic alcohol
Ketone
Secondary alcohol
Cyclic ketone
Hydrocarbon derivative
Organic oxide
Carbonyl group
Organic oxygen compound
Alcohol
Organooxygen compound
Primary alcohol
Aliphatic homopolycyclic compound

Molecular Framework

Aliphatic homopolycyclic compounds

External Descriptors

3-oxo steroid (CHEBI:16485 )
11beta-hydroxy steroid (CHEBI:16485 )
20-oxo steroid (CHEBI:16485 )
21-hydroxy steroid (CHEBI:16485 )
18-hydroxy steroid (CHEBI:16485 )
C21 steroids (gluco/mineralocorticoids, progestogens) and derivatives (C01124 )
Mineralocorticoids (C01124 )
C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030091 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Adrenal Gland

Pathways

Name	SMPDB Link	KEGG Link
Steroidogenesis	SMP00130	map00140
Adrenal Hyperplasia Type 5 or Congenital Adrenal Hyperplasia due to 17 Alpha-hydroxylase Deficiency	SMP00372	Not Available
Corticosterone methyl oxidase I deficiency (CMO I)	SMP00577	Not Available
Corticosterone methyl oxidase II deficiency - CMO II	SMP00578	Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.15 g/L	ALOGPS
logP	1.28	ALOGPS
logP	0.74	ChemAxon
logS	-3.4	ALOGPS
pKa (Strongest Acidic)	13.8	ChemAxon
pKa (Strongest Basic)	-2.8	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	94.83 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	97.77 m³·mol⁻¹	ChemAxon
Polarizability	39.77 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-001i-1639000000-7012f18a6579e07dc571	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positive	splash10-03di-1410290000-5789e767e5a0058f10ed	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_6) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_4) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_5) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_6) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_7) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_8) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_9) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_10) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_11) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_12) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_13) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_14) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_3_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-01r2-0019000000-8a12570d1c1a01069d09	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-004j-0119000000-2b8864299061070cced5	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0019-3494000000-ebcb1ff70c533c4c9459	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-0009000000-0a027947a1d058fb84b7	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-03dl-1019000000-cb3605cb617647c036e0	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-05fr-5094000000-8d05b88622baf6731c7f	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-0009000000-0a10b570836098a58b85	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0zms-3096000000-ebde4d06599fa6ba99f8	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-05fr-1092000000-b70b721681bcc4b0bc16	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-0009000000-728e8f7001bf77edf34e	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-032j-0279000000-46ba785eff196ea28ae2	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-11b9-2690000000-6b57d5653347024bee7a	2021-09-22	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

18-Hydroxycorticosterone is a derivative of corticosterone. It serves as an intermediate in the synthesis of aldosterone by the enzyme aldosterone synthase in the zona glomerulosa. (Wikipedia) 18-Hydroxycorticosterone (18OHB) has low affinity for the mineralocorticoid receptor and mainly originates from the conversion of corticosterone by the aldosterone synthase, although small amounts may be produced by the 11β-hydroxylase. Serum concentrations of 18OHB increase with increased aldosterone synthesis due to sodium depletion and angiotensin II infusion. (7) Accumulation of 18-hydroxycorticosterone in a given organ has been shown to be toxic for the body.

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

This is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.

Minimum Risk Level

Not Available

Health Effects

Chronically high levels of 18-hydroxycorticosterone are associated with at least 3 inborn errors of metabolism including: Adrenal hyperplasia type 5, Corticosterone methyl oxidase I deficiency and Corticosterone methyl oxidase II deficiency.

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

HMDB00319

PubChem Compound ID

11222

ChEMBL ID

Not Available

ChemSpider ID

10748

KEGG ID

C01124

UniProt ID

Not Available

OMIM ID

ChEBI ID

16485

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

18-Hydroxycorticosterone

References

Synthesis Reference

Boudi, Ahmed; Lemoine, Pascale; Viossat, Bernard; Tomas, Alain; Fiet, Jean; Galons, Herve. A convenient synthesis of 18-hydroxycorticosterone and 18-hydroxy-11-desoxycorticosterone via stereospecific hypoiodination of 20-hydroxysteroids. Tetrahedron (1999), 55(16), 5171-5176.

MSDS

T3D4284.pdf

General References

Sonino N, Chow D, Levine LS, New MI: Clinical response to metyrapone as indicated by measurement of mineralocorticoids and glucocorticoids in normal children. Clin Endocrinol (Oxf). 1981 Jan;14(1):31-9. [7226574 ]
Vecsei P, Abdelhamid S, Mittelstadt GV, Lichtwald K, Haack D, Lewicka S: Aldosterone metabolites and possible aldosterone precursors in hypertension. J Steroid Biochem. 1983 Jul;19(1A):345-51. [6887870 ]
Kooner JS, Few JD, Lee CY, Taylor GM, James VH: Investigation of the salivary 18-hydroxycorticosterone:aldosterone ratio in man using a direct assay. J Steroid Biochem Mol Biol. 1991 Mar;38(3):377-82. [2009228 ]
Gomez-Sanchez CE, Clore JN, Estep HL, Watlington CO: Effect of chronic adrenocorticotropin stimulation on the excretion of 18-hydroxycortisol and 18-oxocortisol. J Clin Endocrinol Metab. 1988 Aug;67(2):322-6. [2839536 ]
Honda M, Tsuchiya M, Tamura H, Watanabe H, Izumi Y, Hatano M, Shiratsuchi T, Den K, Kawaoi A, Okano T: In vivo and in vitro studies on steroid metabolism in a case of primary aldosteronism with multiple lesions of adenoma and nodular hyperplasia. Endocrinol Jpn. 1982 Oct;29(5):529-40. [6303762 ]
Vecsei P, Benraad TJ, Hofman J, Abdelhamid S, Haack D, Lichtwald K: Direct radioimmunoassays for "aldosterone" and "18-hydroxycorticosterone" in unprocessed urine, and their use in screening to distinguish primary aldosteronism from hypertension. Clin Chem. 1982 Mar;28(3):453-6. [7067086 ]
Mulatero P, di Cella SM, Monticone S, Schiavone D, Manzo M, Mengozzi G, Rabbia F, Terzolo M, Gomez-Sanchez EP, Gomez-Sanchez CE, Veglio F: 18-hydroxycorticosterone, 18-hydroxycortisol, and 18-oxocortisol in the diagnosis of primary aldosteronism and its subtypes. J Clin Endocrinol Metab. 2012 Mar;97(3):881-9. doi: 10.1210/jc.2011-2384. Epub 2012 Jan 11. [22238407 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Mineralocorticoid receptor

General Function:: Zinc ion binding
Specific Function:: Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.
Gene Name:: NR3C2
Uniprot ID:: P08235
Molecular Weight:: 107066.575 Da

18-Hydroxycorticosterone (T3D4284)

Structure for T3D4284: 18-Hydroxycorticosterone

Targets