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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2006-08-13 04:25:20 UTC
Update Date2019-07-23 05:45:52 UTC
HMDB IDHMDB0003759
Secondary Accession Numbers
  • HMDB03759
Metabolite Identification
Common Name5a-Pregnane-3,20-dione
Description5a-Pregnane-3,20-dione is a biologically active 5-alpha-reduced metabolite of plasma progesterone. It is the immediate precursor of 5-alpha-pregnan-3-alpha-ol-20-one (allopregnanolone), a neuroactive steroid that binds with GABA(A) receptor.
Structure
Data?1563860752
Synonyms
ValueSource
3,20-AllopregnanedioneChEBI
3,20-Dioxo-5alpha-pregnaneChEBI
5-alpha-DihydroprogesteroneChEBI
5alpha-DihydroprogesteroneChEBI
3,20-Dioxo-5a-pregnaneGenerator
3,20-Dioxo-5α-pregnaneGenerator
5-a-DihydroprogesteroneGenerator
5-Α-dihydroprogesteroneGenerator
5a-DihydroprogesteroneGenerator
5Α-dihydroprogesteroneGenerator
5-alpha-Pregnane-3,20-dioneHMDB
5a-Pregnan-3,20-dioneHMDB
5alpha-Pregnan-3,20-dioneHMDB
5alpha-Pregnane-3,20-dioneHMDB
5b-Pregnane-3,20-dioneHMDB
5beta-Pregnane-3,20-dioneHMDB
Allopregnan-3,20-dioneHMDB
Pregnane-3,20-dioneHMDB
5 alpha DihydroprogesteroneHMDB
5 beta Pregnane 3,20 dioneHMDB
5 beta-Pregnane-3,20-dioneHMDB
5-beta-DihydroprogesteroneHMDB
5alpha-DHPHMDB
3,20-Allopregnanedione, (5beta,13alpha,17alpha)-isomerHMDB
5 alpha PregnanedioneHMDB
5alpha DHPHMDB
5alpha Pregnane 3,20 dioneHMDB
5beta DHPHMDB
5beta-DHPHMDB
3,20 AllopregnanedioneHMDB
3,20-Allopregnanedione, (5alpha)-isomerHMDB
5 alpha Pregnane 3,20 dioneHMDB
5 alpha-DihydroprogesteroneHMDB
5 alpha-Pregnane-3,20-dioneHMDB
5 beta DihydroprogesteroneHMDB
5-alpha-PregnanedioneHMDB
Chemical FormulaC21H32O2
Average Molecular Weight316.4776
Monoisotopic Molecular Weight316.240230268
IUPAC Name(1S,2S,7S,10R,11S,14S,15S)-14-acetyl-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-5-one
Traditional Name5a-pregnane-3,20-dione
CAS Registry Number566-65-4
SMILES
[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]2([H])CC(=O)CC[C@]12C
InChI Identifier
InChI=1S/C21H32O2/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/h14,16-19H,4-12H2,1-3H3/t14-,16-,17+,18-,19-,20-,21+/m0/s1
InChI KeyXMRPGKVKISIQBV-BJMCWZGWSA-N
Chemical Taxonomy
Description 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-oxo-5-alpha-steroid
  • Oxosteroid
  • 3-oxosteroid
  • Cyclic ketone
  • Ketone
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point200 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0013 g/LALOGPS
logP4.06ALOGPS
logP4.19ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)19.34ChemAxon
pKa (Strongest Basic)-7.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity91.88 m³·mol⁻¹ChemAxon
Polarizability37.86 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0umu-9810000000-76ef4cf96a30792f4d73JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0umu-9810000000-7151501afadd028a99ecJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0umu-9810000000-76ef4cf96a30792f4d73JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0umu-9810000000-7151501afadd028a99ecJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0f76-4910000000-81546b52d59f9518cb0cJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0f76-4910000000-dbf8c4ca357b5f19f54dJSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0fkj-0391000000-1964b2faffc1ae5ab9b4JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0159000000-fdffc096796499edd3d4JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05p2-0492000000-3f8a5badfddf1ced4edfJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052f-2590000000-932901e825351ef60bc4JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0019000000-8848319d0e10bc22bc8cJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0039000000-04efc7afcedbf957d0eeJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-006t-1090000000-259e4f493b06ea76a0d6JSpectraViewer | MoNA
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biospecimen Locations
  • Blood
Tissue Locations
  • Fibroblasts
  • Testes
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0171 +/- 0.0056 uMAdult (>18 years old)FemaleNormal details
BloodDetected but not Quantified Adult (>18 years old)Female
Normal
details
BloodDetected and Quantified0.055 +/- 0.025 uMAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0239 +/- 0.0084 uMAdult (>18 years old)Female
Prepartum depression
details
BloodDetected but not Quantified Adult (>18 years old)Female
Schizophrenia
details
BloodDetected and Quantified0.042 +/- 0.025 uMAdult (>18 years old)Both
Psychiatric disorder
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. [PubMed:16959481 ]
Major depressive disorder
  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. [PubMed: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. [PubMed:11739473 ]
Schizophrenia
  1. Bicikova M, Hill M, Ripova D, Mohr P, Hampl R: Determination of steroid metabolome as a possible tool for laboratory diagnosis of schizophrenia. J Steroid Biochem Mol Biol. 2013 Jan;133:77-83. doi: 10.1016/j.jsbmb.2012.08.009. Epub 2012 Aug 24. [PubMed:22944140 ]
Associated OMIM IDs
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB023222
KNApSAcK IDNot Available
Chemspider ID83782
KEGG Compound IDC03681
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia Link5%CE%B1-Dihydroprogesterone
METLIN ID6981
PubChem Compound92810
PDB IDNot Available
ChEBI ID28952
References
Synthesis ReferenceValenta, Zdenek. Steroid total synthesis and intermediates. U.S. (1975), 14 pp.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Kwan TK, Kraevskaya MA, Makin HL, Trafford DJ, Gower DB: Use of gas chromatographic-mass spectrometric techniques in studies of androst-16-ene and androgen biosynthesis in human testis; cytosolic specific binding of 5alpha-androst-16-en-3-one. J Steroid Biochem Mol Biol. 1997 Jan;60(1-2):137-46. [PubMed:9182868 ]
  2. Zhang J, Ming LJ, Sjovall J, Cook HW, Ridgway ND, Byers DM: Progesterone metabolism in human fibroblasts is independent of P-glycoprotein levels and Niemann-Pick type C disease. J Steroid Biochem Mol Biol. 1999 Sep-Oct;70(4-6):123-31. [PubMed:10622400 ]
  3. Sandow J, Engelbart K, von Rechenberg W: The different mechanisms for suppression of pituitary and testicular function. Med Biol. 1986;63(5-6):192-200. [PubMed:3010006 ]
  4. Jarczok T, Zwirner M, Schindler AE: Progesterone and 5 alpha-pregnane-3,20-dione in human amniotic fluid. Exp Clin Endocrinol. 1987 Mar;89(1):39-47. [PubMed:3595731 ]
  5. Gomez-Sanchez EP, Cox D, Foecking M, Ganjam V, Gomez-Sanchez CE: 11 beta-hydroxysteroid dehydrogenases of the choriocarcinoma cell line JEG-3 and their inhibition by glycyrrhetinic acid and other natural substances. Steroids. 1996 Mar;61(3):110-5. [PubMed:8852827 ]
  6. 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. [PubMed:11739473 ]
  7. Chantilis S, Dombroski R, Shackleton CH, Casey ML, MacDonald PC: Metabolism of 5 alpha-dihydroprogesterone in women and men: 3 beta- and 3 alpha-,6 alpha-dihydroxy-5 alpha-pregnan-20-ones are major urinary metabolites. J Clin Endocrinol Metab. 1996 Oct;81(10):3644-9. [PubMed:8855816 ]
  8. Zwirner M, Fawzy MM, Bopp FC, Klemm-Wolfgram E, Handschuh D, Voelter W, Schindler AE: Radioimmunoassay of 5 alpha-pregnane-3,20-dione. A metabolite of placental progesterone. Arch Gynecol. 1983;233(4):229-40. [PubMed:6660916 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol). Also has some 20-alpha-hydroxysteroid dehydrogenase activity. The biotransformation of the pesticide chlordecone (kepone) to its corresponding alcohol leads to increased biliary excretion of the pesticide and concomitant reduction of its neurotoxicity since bile is the major excretory route.
Gene Name:
AKR1C4
Uniprot ID:
P17516
Molecular weight:
37094.57
Reactions
3a-Hydroxy-5b-pregnane-20-one + NAD → 5a-Pregnane-3,20-dione + NADH + Hydrogen Iondetails
3a-Hydroxy-5b-pregnane-20-one + NADP → 5a-Pregnane-3,20-dione + NADPH + Hydrogen Iondetails
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
General function:
Involved in oxidoreductase activity
Specific function:
Efficiently catalyzes the reduction of progesterone, androstenedione, 17-alpha-hydroxyprogesterone and testosterone to 5-beta-reduced metabolites. The bile acid intermediates 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one and 7-alpha-hydroxy-4-cholesten-3-one can also act as substrates.
Gene Name:
AKR1D1
Uniprot ID:
P51857
Molecular weight:
32889.38
Reactions
5a-Pregnane-3,20-dione + Acceptor → Progesterone + Reduced acceptordetails
Progesterone + NADPH + Hydrogen Ion → 5a-Pregnane-3,20-dione + NADPdetails