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Record Information
Version3.6
Creation Date2006-08-16 15:10:22 UTC
Update Date2016-02-11 01:04:42 UTC
HMDB IDHMDB01449
Secondary Accession NumbersNone
Metabolite Identification
Common NameAllopregnanolone
DescriptionAllopregnanolone is a neuroactive metabolite of progesterone and a barbiturate-like modulator of central gamma-aminobutyric acid receptors that modify a range of behaviors, including the stress response. is a steroid created in the body when progesterone, the female sex hormone, is metabolized. Typically, THP (allopregnanolone) is released in the brain in response to stress, and quiets the neural system within 30 minutes of escalation. This steroid hormone has recently been found to be responsible for the extreme mood swings found in teenagers. In adults and pre-pubescent chlidren THP normally helps soothe the activity of brain cells by binding to GABA receptors that inhibit accelerating electrical activity. However, in pubescent teenagers THP actually becomes a GABA receptor antagonist. GABA (gamma-aminobutyric acid) is the primary inhibitory neurotransmitter in the brain with most sedatives (tranquilizers, anesthetics and alcohol) acting on the GABA receptor.
Structure
Thumb
Synonyms
ValueSource
(3alpha,5alpha)-3-Hydroxypregnan-20-oneChEBI
3alpha-OH DHPChEBI
Allopregnan-3alpha-ol-20-oneChEBI
(3a,5a)-3-Hydroxypregnan-20-oneGenerator
(3α,5α)-3-hydroxypregnan-20-oneGenerator
(+)-3a-Hydroxy-5a-pregnan-20-oneHMDB
(3a)-AllopregnanoloneHMDB
3-a-TetrahydroprogesteroneHMDB
3-alpha-TetrahydroprogesteroneHMDB
3a,5a-PregnanoloneHMDB
3a,5a-TetrahydroprogesteroneHMDB
3a,5a-THPHMDB
3a-Hydroxy-5a-dihydroprogesteroneHMDB
3a-Hydroxy-5a-pregnan-20-oneHMDB
3a-Hydroxy-5a-pregnane-20-oneHMDB
5a-Pregnan-3a-ol-20-oneHMDB
5a-Pregnane-3a-ol-20-oneHMDB
Allopregnan-3a-ol-20-oneHMDB
AllotetrahydroprogesteroneHMDB
Chemical FormulaC21H34O2
Average Molecular Weight318.4935
Monoisotopic Molecular Weight318.255880332
IUPAC Name1-[(1S,2S,5R,7S,10R,11S,14S,15S)-5-hydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-14-yl]ethan-1-one
Traditional Name3a-hydroxy-5a-pregnan-20-one
CAS Registry Number516-54-1
SMILES
[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]2([H])C[C@H](O)CC[C@]12C
InChI Identifier
InChI=1S/C21H34O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h14-19,23H,4-12H2,1-3H3/t14-,15+,16-,17+,18-,19-,20-,21+/m0/s1
InChI KeyInChIKey=AURFZBICLPNKBZ-SYBPFIFISA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassPregnane steroids
Direct ParentGluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
Substituents
  • Progestogin-skeleton
  • 20-oxosteroid
  • 3-alpha-hydroxysteroid
  • Oxosteroid
  • Hydroxysteroid
  • 3-hydroxysteroid
  • Cyclic alcohol
  • Secondary alcohol
  • Ketone
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
  • 3-hydroxy-5alpha-pregnan-20-one (CHEBI:50169 )
  • C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030156 )
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Hormones, Membrane component
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point177 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0014 mg/mLALOGPS
logP4.28ALOGPS
logP3.99ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)18.3ChemAxon
pKa (Strongest Basic)-1.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity92.91 m3·mol-1ChemAxon
Polarizability38.57 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)splash10-0udi-6910000000-837b37f206729753b640View in MoNA
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.01 +/- 0.003 uMAdult (>18 years old)FemaleNormal details
BloodDetected and Quantified0.001 +/- 0.00025 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.0002 +/- 0.000062 uMAdult (>18 years old)MaleNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00016 +/- 0.00011 uMAdult (>18 years old)MaleNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.011 +/- 0.002 uMAdult (>18 years old)FemalePrepartum depression details
BloodDetected and Quantified0.001 +/- 0.00028 uMAdult (>18 years old)Both
Psychiatric disorder
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000150 +/- 0.0000015 uMAdult (>18 years old)Both
Major depression
details
Associated Disorders and Diseases
Disease References
Alcoholism
  1. Nieminen LR, Makino KK, Mehta N, Virkkunen M, Kim HY, Hibbeln JR: Relationship between omega-3 fatty acids and plasma neuroactive steroids in alcoholism, depression and controls. Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):309-14. Epub 2006 Sep 7. [16959481 ]
Major depressive disorder
  1. Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, Guidotti A: Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3239-44. [9501247 ]
  2. Nieminen LR, Makino KK, Mehta N, Virkkunen M, Kim HY, Hibbeln JR: Relationship between omega-3 fatty acids and plasma neuroactive steroids in alcoholism, depression and controls. Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):309-14. Epub 2006 Sep 7. [16959481 ]
Prepartum depression
  1. Pearson Murphy BE, Steinberg SI, Hu FY, Allison CM: Neuroactive ring A-reduced metabolites of progesterone in human plasma during pregnancy: elevated levels of 5 alpha-dihydroprogesterone in depressed patients during the latter half of pregnancy. J Clin Endocrinol Metab. 2001 Dec;86(12):5981-7. [11739473 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022630
KNApSAcK IDNot Available
Chemspider ID83760
KEGG Compound IDC13712
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkAllopregnanolone
NuGOwiki LinkHMDB01449
Metagene LinkHMDB01449
METLIN IDNot Available
PubChem Compound92786
PDB IDNot Available
ChEBI ID50169
References
Synthesis ReferenceWiebe, J. P.; Deline, C.; Buckingham, K. D.; Dave, Vinod; Stothers, J. B. Synthesis of the allylic gonadal steroids, 3a-hydroxy-4-pregnen-20-one and 3a-hydroxy-4-androsten-17-one, and of 3a-hydroxy-5a-pregnan-20-one. Steroids (1985), 45(1), 39-51.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Kim YS, Zhang H, Kim HY: Profiling neurosteroids in cerebrospinal fluids and plasma by gas chromatography/electron capture negative chemical ionization mass spectrometry. Anal Biochem. 2000 Jan 15;277(2):187-95. [10625505 ]
  2. Pearson Murphy BE, Steinberg SI, Hu FY, Allison CM: Neuroactive ring A-reduced metabolites of progesterone in human plasma during pregnancy: elevated levels of 5 alpha-dihydroprogesterone in depressed patients during the latter half of pregnancy. J Clin Endocrinol Metab. 2001 Dec;86(12):5981-7. [11739473 ]
  3. Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, Guidotti A: Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3239-44. [9501247 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.
Gene Name:
AKR1C3
Uniprot ID:
P42330
Molecular weight:
36866.91
Reactions
5a-Pregnane-3,20-dione + NADPH + Hydrogen Ion → Allopregnanolone + NADPdetails
General function:
Involved in oxidoreductase activity
Specific function:
Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.
Gene Name:
AKR1C1
Uniprot ID:
Q04828
Molecular weight:
36788.02
Reactions
5a-Pregnane-3,20-dione + NADPH + Hydrogen Ion → Allopregnanolone + NADPdetails
General function:
Involved in oxidoreductase activity
Specific function:
Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Has a high bile-binding ability.
Gene Name:
AKR1C2
Uniprot ID:
P52895
Molecular weight:
15747.91
Reactions
5a-Pregnane-3,20-dione + NADPH + Hydrogen Ion → Allopregnanolone + NADPdetails