Metabolism of steroid hormones (Homo sapiens)

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122320352, 8, 1118, 28, 316, 3311, 3910, 13, 21, 3924, 427308, 1411, 17, 19, 22, 419, 16, 25, 26, 294, 11, 32, 341244124438, 4315, 3711, 446, 3338, 432, 810, 13, 21, 39458, 143, 52710, 13, 21, 3924, 426, 33, 3614439mitochondrial matrixcytosolendoplasmic reticulum lumenmitochondrial intermembrane spaceH+H+NADHNADPHCH3CHOPOMC(138-176)TSPO:BZRAP1CYP11A1:FDXR:FDX1,FDX1L (red.)H+POMC(138-176)NADPHNADP+H+H2OCYP11A1 CGA NADPHNADP+STARD6 NADP+BZRAP1 EST17bNADP+H+CYP11A1:FDXR:FDX1,FDX1L (ox.)11DCORSTHCOOHHSD17B1 TESTPOMC(138-176)H2ONADPHSTARD4 STAR 17aHPREGCYP17A1HSD17B14 H+11DCORTNADPHNADPHCORTAKR1B15NADPHO2O2NADP+(2Fe-2S)2+ H+NADP+O2HSD17B1 dimerNADPHHSD17B2HSD2B1 or HSD3B2dimerNADP+H+H+P4H+PREGLHB PREGCytochrome P450(CYP11B1 based)HSD11B2, HSD11B1dimerH+NAD+HSD17B14 tetramerCGA FDXR O2HSD17B12 H2OCORTSTARD3 17aHPROGDHTESTHSD17B11CYP11B1 POMC(138-176)NADP+HSD17B3-likeProteinsSRD5A1-3H2OH2OHSD11B1 DHEAO2cholesterol NADP+MePeOHNADP+H2O(2Fe-2S)(1+) ISCALSTARD3:STARD3NL,STARD4,6:CHOLNADP+H+CORSTH2ONADP+AKR1B1NADPHO2STAR:CHOLO2E1NADP+O2H2ONADPHH+CYP21A2NADPHCHOL E1CYP19A1H+CHOLNADHpregn-5-ene-3,20-dione-17-olSTARD3NL E2CYP11A1 O2NADPHNADPHSTARD4 HSD17B3 HSD11B2 LHB STARD3 NADP+NADPHISCALCH3CHOSTARD3:STARD3NL,STARD4,6NADPHH2ONADPHTSPO H2OH+CHOLHSD3B2 COR11DCORST11-deoxycortisolALDOANDSTO2CYP11B2FDX1L H+NAD+POMC(138-176)18HCORSTglyco-LutropinNADP+STARSTARD6 H+FDX1 22b-HCHOLO2O2FDX1 FDX1L EST17bSRD5A2 pregn-5-ene-3,20-dioneNADP+H2ONADPHP4NADP+NADPH17aHPROGH+SRD5A3 H+NADP+20a,22b-DHCHOLH2OE1glyco-LutropinH+STARD3NL CYP11B2 SRD5A1 HSD3B1 FDXR 40


Description

Steroid hormones are synthesized primarily in the adrenal gland and gonads. They regulate energy metabolism and stress responses (glucocorticoids), salt balance (mineralocorticoids), and sexual development and function (androgens and estrogens). All steroids are synthesized from cholesterol. Steroid hormone synthesis is largely regulated at the initial steps of cholesterol mobilization and transport into the mitochondrial matrix for conversion to pregnenolone. In the body, the fate of pregnenolone is tissue-specific: in the zona fasciculata of the adrenal cortex it is converted to cortisol, in the zona glomerulosa to aldosterone, and in the gonads to testosterone and then to estrone and estradiol. These pathways are outlined in the figure below, which also details the sites on the cholesterol molecule that undergo modification in the course of these reactions. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 196071
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: Jassal, Bijay

Quality Tags

Ontology Terms

 

Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
101645view11:51, 1 November 2018ReactomeTeamreactome version 66
101181view21:38, 31 October 2018ReactomeTeamreactome version 65
100707view20:10, 31 October 2018ReactomeTeamreactome version 64
100257view16:56, 31 October 2018ReactomeTeamreactome version 63
99810view15:20, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99354view12:48, 31 October 2018ReactomeTeamreactome version 62
94495view09:01, 14 September 2017Mkutmonreactome version 61
87913view12:59, 25 July 2016RyanmillerOntology Term : 'classic metabolic pathway' added !
83163view10:14, 18 November 2015ReactomeTeamVersion54
81521view13:03, 21 August 2015ReactomeTeamVersion53
76990view08:28, 17 July 2014ReactomeTeamFixed remaining interactions
76695view12:06, 16 July 2014ReactomeTeamFixed remaining interactions
76021view10:08, 11 June 2014ReactomeTeamRe-fixing comment source
75730view11:20, 10 June 2014ReactomeTeamReactome 48 Update
75080view14:02, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74727view08:48, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
(2Fe-2S)(1+) MetaboliteCHEBI:33738 (ChEBI)
(2Fe-2S)2+ MetaboliteCHEBI:33737 (ChEBI)
11-deoxycortisolMetaboliteCHEBI:28324 (ChEBI)
11DCORSTMetaboliteCHEBI:16973 (ChEBI)
11DCORTMetaboliteCHEBI:28324 (ChEBI)
17aHPREGMetaboliteCHEBI:28750 (ChEBI)
17aHPROGMetaboliteCHEBI:17252 (ChEBI)
18HCORSTMetaboliteCHEBI:16485 (ChEBI)
20a,22b-DHCHOLMetaboliteCHEBI:1294 (ChEBI)
22b-HCHOLMetaboliteCHEBI:1301 (ChEBI)
AKR1B15ProteinC9JRZ8 (Uniprot-TrEMBL)
AKR1B1ProteinP15121 (Uniprot-TrEMBL)
ALDOMetaboliteCHEBI:27584 (ChEBI)
ANDSTMetaboliteCHEBI:16422 (ChEBI)
BZRAP1 ProteinO95153 (Uniprot-TrEMBL)
CGA ProteinP01215 (Uniprot-TrEMBL)
CH3CHOMetaboliteCHEBI:15343 (ChEBI)
CHOL MetaboliteCHEBI:16113 (ChEBI)
CHOLMetaboliteCHEBI:16113 (ChEBI)
CORMetaboliteCHEBI:16962 (ChEBI)
CORSTMetaboliteCHEBI:16827 (ChEBI)
CORTMetaboliteCHEBI:17650 (ChEBI)
CYP11A1 ProteinP05108 (Uniprot-TrEMBL)
CYP11A1:FDXR:FDX1,FDX1L (ox.)ComplexR-HSA-5580259 (Reactome)
CYP11A1:FDXR:FDX1,FDX1L (red.)ComplexR-HSA-5580249 (Reactome)
CYP11B1 ProteinP15538 (Uniprot-TrEMBL)
CYP11B2 ProteinP19099 (Uniprot-TrEMBL)
CYP11B2ProteinP19099 (Uniprot-TrEMBL)
CYP17A1ProteinP05093 (Uniprot-TrEMBL)
CYP19A1ProteinP11511 (Uniprot-TrEMBL)
CYP21A2ProteinP08686 (Uniprot-TrEMBL)
Cytochrome P450 (CYP11B1 based)ComplexR-HSA-3219421 (Reactome) This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
DHEAMetaboliteCHEBI:28689 (ChEBI)
DHTESTMetaboliteCHEBI:16330 (ChEBI)
E1MetaboliteCHEBI:17263 (ChEBI)
E2MetaboliteCHEBI:16469 (ChEBI)
EST17bMetaboliteCHEBI:16469 (ChEBI)
FDX1 ProteinP10109 (Uniprot-TrEMBL)
FDX1L ProteinQ6P4F2 (Uniprot-TrEMBL)
FDXR ProteinP22570 (Uniprot-TrEMBL)
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HCOOHMetaboliteCHEBI:30751 (ChEBI)
HSD11B1 ProteinP28845 (Uniprot-TrEMBL)
HSD11B2 ProteinP80365 (Uniprot-TrEMBL)
HSD11B2, HSD11B1 dimerComplexR-HSA-5693385 (Reactome)
HSD17B1 ProteinP14061 (Uniprot-TrEMBL)
HSD17B1 dimerComplexR-HSA-804966 (Reactome)
HSD17B11ProteinQ8NBQ5 (Uniprot-TrEMBL)
HSD17B12 ProteinQ53GQ0 (Uniprot-TrEMBL)
HSD17B14 ProteinQ9BPX1 (Uniprot-TrEMBL)
HSD17B14 tetramerComplexR-HSA-6810583 (Reactome)
HSD17B2ProteinP37059 (Uniprot-TrEMBL)
HSD17B3 ProteinP37058 (Uniprot-TrEMBL)
HSD17B3-like ProteinsComplexR-HSA-3902489 (Reactome) This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
HSD2B1 or HSD3B2 dimerComplexR-HSA-196357 (Reactome)
HSD3B1 ProteinP14060 (Uniprot-TrEMBL)
HSD3B2 ProteinP26439 (Uniprot-TrEMBL)
ISCALMetaboliteCHEBI:17998 (ChEBI)
LHB ProteinP01229 (Uniprot-TrEMBL)
MePeOHMetaboliteCHEBI:63910 (ChEBI)
NAD+MetaboliteCHEBI:15846 (ChEBI)
NADHMetaboliteCHEBI:16908 (ChEBI)
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteCHEBI:16474 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
P4MetaboliteCHEBI:17026 (ChEBI)
POMC(138-176)ProteinP01189 (Uniprot-TrEMBL)
PREGMetaboliteCHEBI:16581 (ChEBI)
SRD5A1 ProteinP18405 (Uniprot-TrEMBL)
SRD5A1-3ComplexR-HSA-469656 (Reactome)
SRD5A2 ProteinP31213 (Uniprot-TrEMBL)
SRD5A3 ProteinQ9H8P0 (Uniprot-TrEMBL)
STAR ProteinP49675 (Uniprot-TrEMBL)
STAR:CHOLComplexR-HSA-196090 (Reactome)
STARD3 ProteinQ14849 (Uniprot-TrEMBL)
STARD3:STARD3NL, STARD4,6:CHOLComplexR-HSA-196124 (Reactome)
STARD3:STARD3NL, STARD4,6ComplexR-HSA-196094 (Reactome)
STARD3NL ProteinO95772 (Uniprot-TrEMBL)
STARD4 ProteinQ96DR4 (Uniprot-TrEMBL)
STARD6 ProteinP59095 (Uniprot-TrEMBL)
STARProteinP49675 (Uniprot-TrEMBL)
TESTMetaboliteCHEBI:17347 (ChEBI)
TSPO ProteinP30536 (Uniprot-TrEMBL)
TSPO:BZRAP1ComplexR-HSA-8951857 (Reactome)
cholesterol MetaboliteCHEBI:16113 (ChEBI)
glyco-LutropinComplexR-HSA-378969 (Reactome)
pregn-5-ene-3,20-dione-17-olMetaboliteCHEBI:63843 (ChEBI)
pregn-5-ene-3,20-dioneMetaboliteCHEBI:63837 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
11-deoxycortisolArrowR-HSA-193981 (Reactome)
11-deoxycortisolR-HSA-194025 (Reactome)
11DCORSTArrowR-HSA-193964 (Reactome)
11DCORSTArrowR-HSA-193996 (Reactome)
11DCORSTR-HSA-193996 (Reactome)
11DCORSTR-HSA-194017 (Reactome)
11DCORTArrowR-HSA-194025 (Reactome)
11DCORTR-HSA-193997 (Reactome)
17aHPREGArrowR-HSA-193068 (Reactome)
17aHPREGR-HSA-193070 (Reactome)
17aHPREGR-HSA-196372 (Reactome)
17aHPROGArrowR-HSA-193072 (Reactome)
17aHPROGArrowR-HSA-193961 (Reactome)
17aHPROGR-HSA-193099 (Reactome)
17aHPROGR-HSA-193981 (Reactome)
18HCORSTArrowR-HSA-193995 (Reactome)
18HCORSTR-HSA-193965 (Reactome)
20a,22b-DHCHOLArrowR-HSA-193065 (Reactome)
20a,22b-DHCHOLR-HSA-193101 (Reactome)
22b-HCHOLArrowR-HSA-193054 (Reactome)
22b-HCHOLR-HSA-193065 (Reactome)
AKR1B15mim-catalysisR-HSA-5696822 (Reactome)
AKR1B1mim-catalysisR-HSA-196060 (Reactome)
ALDOArrowR-HSA-193965 (Reactome)
ANDSTArrowR-HSA-193073 (Reactome)
ANDSTArrowR-HSA-193099 (Reactome)
ANDSTR-HSA-193060 (Reactome)
ANDSTR-HSA-193064 (Reactome)
CH3CHOArrowR-HSA-193070 (Reactome)
CH3CHOArrowR-HSA-193099 (Reactome)
CHOLArrowR-HSA-196086 (Reactome)
CHOLArrowR-HSA-8951850 (Reactome)
CHOLR-HSA-193054 (Reactome)
CHOLR-HSA-8951850 (Reactome)
CORArrowR-HSA-194023 (Reactome)
CORSTArrowR-HSA-194017 (Reactome)
CORSTR-HSA-193995 (Reactome)
CORTArrowR-HSA-193997 (Reactome)
CORTArrowR-HSA-194036 (Reactome)
CORTR-HSA-194023 (Reactome)
CORTR-HSA-194036 (Reactome)
CYP11A1:FDXR:FDX1,FDX1L (ox.)ArrowR-HSA-193101 (Reactome)
CYP11A1:FDXR:FDX1,FDX1L (red.)R-HSA-193101 (Reactome)
CYP11A1:FDXR:FDX1,FDX1L (red.)mim-catalysisR-HSA-193054 (Reactome)
CYP11A1:FDXR:FDX1,FDX1L (red.)mim-catalysisR-HSA-193065 (Reactome)
CYP11A1:FDXR:FDX1,FDX1L (red.)mim-catalysisR-HSA-193101 (Reactome)
CYP11B2mim-catalysisR-HSA-193965 (Reactome)
CYP11B2mim-catalysisR-HSA-193995 (Reactome)
CYP11B2mim-catalysisR-HSA-194017 (Reactome)
CYP17A1mim-catalysisR-HSA-193068 (Reactome)
CYP17A1mim-catalysisR-HSA-193070 (Reactome)
CYP17A1mim-catalysisR-HSA-193072 (Reactome)
CYP17A1mim-catalysisR-HSA-193099 (Reactome)
CYP19A1mim-catalysisR-HSA-193060 (Reactome)
CYP19A1mim-catalysisR-HSA-193143 (Reactome)
CYP21A2mim-catalysisR-HSA-193964 (Reactome)
CYP21A2mim-catalysisR-HSA-193981 (Reactome)
Cytochrome P450 (CYP11B1 based)mim-catalysisR-HSA-193997 (Reactome)
DHEAArrowR-HSA-193070 (Reactome)
DHEAR-HSA-193073 (Reactome)
DHTESTArrowR-HSA-469659 (Reactome)
E1ArrowR-HSA-193060 (Reactome)
E1ArrowR-HSA-5693390 (Reactome)
E1ArrowR-HSA-5696822 (Reactome)
E1ArrowR-HSA-6810594 (Reactome)
E1ArrowR-HSA-8862137 (Reactome)
E1R-HSA-804969 (Reactome)
E2R-HSA-6810594 (Reactome)
E2R-HSA-8862137 (Reactome)
EST17bArrowR-HSA-193143 (Reactome)
EST17bArrowR-HSA-804969 (Reactome)
EST17bR-HSA-5693390 (Reactome)
EST17bR-HSA-5696822 (Reactome)
H+ArrowR-HSA-193073 (Reactome)
H+ArrowR-HSA-194023 (Reactome)
H+ArrowR-HSA-196350 (Reactome)
H+ArrowR-HSA-196372 (Reactome)
H+ArrowR-HSA-5693390 (Reactome)
H+ArrowR-HSA-5696822 (Reactome)
H+ArrowR-HSA-6810594 (Reactome)
H+ArrowR-HSA-8862137 (Reactome)
H+R-HSA-193054 (Reactome)
H+R-HSA-193060 (Reactome)
H+R-HSA-193064 (Reactome)
H+R-HSA-193065 (Reactome)
H+R-HSA-193068 (Reactome)
H+R-HSA-193070 (Reactome)
H+R-HSA-193072 (Reactome)
H+R-HSA-193099 (Reactome)
H+R-HSA-193101 (Reactome)
H+R-HSA-193143 (Reactome)
H+R-HSA-193964 (Reactome)
H+R-HSA-193965 (Reactome)
H+R-HSA-193981 (Reactome)
H+R-HSA-193995 (Reactome)
H+R-HSA-193997 (Reactome)
H+R-HSA-194017 (Reactome)
H+R-HSA-196060 (Reactome)
H+R-HSA-469659 (Reactome)
H+R-HSA-804969 (Reactome)
H2OArrowR-HSA-193054 (Reactome)
H2OArrowR-HSA-193060 (Reactome)
H2OArrowR-HSA-193065 (Reactome)
H2OArrowR-HSA-193068 (Reactome)
H2OArrowR-HSA-193070 (Reactome)
H2OArrowR-HSA-193072 (Reactome)
H2OArrowR-HSA-193099 (Reactome)
H2OArrowR-HSA-193101 (Reactome)
H2OArrowR-HSA-193143 (Reactome)
H2OArrowR-HSA-193964 (Reactome)
H2OArrowR-HSA-193965 (Reactome)
H2OArrowR-HSA-193981 (Reactome)
H2OArrowR-HSA-193995 (Reactome)
H2OArrowR-HSA-193997 (Reactome)
H2OArrowR-HSA-194017 (Reactome)
HCOOHArrowR-HSA-193060 (Reactome)
HCOOHArrowR-HSA-193143 (Reactome)
HSD11B2, HSD11B1 dimermim-catalysisR-HSA-194023 (Reactome)
HSD17B1 dimermim-catalysisR-HSA-804969 (Reactome)
HSD17B11mim-catalysisR-HSA-5693390 (Reactome)
HSD17B14 tetramermim-catalysisR-HSA-6810594 (Reactome)
HSD17B2mim-catalysisR-HSA-8862137 (Reactome)
HSD17B3-like Proteinsmim-catalysisR-HSA-193064 (Reactome)
HSD2B1 or HSD3B2 dimermim-catalysisR-HSA-193052 (Reactome)
HSD2B1 or HSD3B2 dimermim-catalysisR-HSA-193073 (Reactome)
HSD2B1 or HSD3B2 dimermim-catalysisR-HSA-193961 (Reactome)
HSD2B1 or HSD3B2 dimermim-catalysisR-HSA-196350 (Reactome)
HSD2B1 or HSD3B2 dimermim-catalysisR-HSA-196372 (Reactome)
ISCALArrowR-HSA-193101 (Reactome)
ISCALArrowR-HSA-196125 (Reactome)
ISCALR-HSA-196060 (Reactome)
ISCALR-HSA-196125 (Reactome)
MePeOHArrowR-HSA-196060 (Reactome)
NAD+R-HSA-193073 (Reactome)
NAD+R-HSA-196350 (Reactome)
NAD+R-HSA-196372 (Reactome)
NADHArrowR-HSA-193073 (Reactome)
NADHArrowR-HSA-196350 (Reactome)
NADHArrowR-HSA-196372 (Reactome)
NADP+ArrowR-HSA-193054 (Reactome)
NADP+ArrowR-HSA-193060 (Reactome)
NADP+ArrowR-HSA-193064 (Reactome)
NADP+ArrowR-HSA-193065 (Reactome)
NADP+ArrowR-HSA-193068 (Reactome)
NADP+ArrowR-HSA-193070 (Reactome)
NADP+ArrowR-HSA-193072 (Reactome)
NADP+ArrowR-HSA-193099 (Reactome)
NADP+ArrowR-HSA-193101 (Reactome)
NADP+ArrowR-HSA-193143 (Reactome)
NADP+ArrowR-HSA-193964 (Reactome)
NADP+ArrowR-HSA-193965 (Reactome)
NADP+ArrowR-HSA-193981 (Reactome)
NADP+ArrowR-HSA-193995 (Reactome)
NADP+ArrowR-HSA-193997 (Reactome)
NADP+ArrowR-HSA-194017 (Reactome)
NADP+ArrowR-HSA-196060 (Reactome)
NADP+ArrowR-HSA-469659 (Reactome)
NADP+ArrowR-HSA-804969 (Reactome)
NADP+R-HSA-194023 (Reactome)
NADP+R-HSA-5693390 (Reactome)
NADP+R-HSA-5696822 (Reactome)
NADP+R-HSA-6810594 (Reactome)
NADP+R-HSA-8862137 (Reactome)
NADPHArrowR-HSA-194023 (Reactome)
NADPHArrowR-HSA-5693390 (Reactome)
NADPHArrowR-HSA-5696822 (Reactome)
NADPHArrowR-HSA-6810594 (Reactome)
NADPHArrowR-HSA-8862137 (Reactome)
NADPHR-HSA-193054 (Reactome)
NADPHR-HSA-193060 (Reactome)
NADPHR-HSA-193064 (Reactome)
NADPHR-HSA-193065 (Reactome)
NADPHR-HSA-193068 (Reactome)
NADPHR-HSA-193070 (Reactome)
NADPHR-HSA-193072 (Reactome)
NADPHR-HSA-193099 (Reactome)
NADPHR-HSA-193101 (Reactome)
NADPHR-HSA-193143 (Reactome)
NADPHR-HSA-193964 (Reactome)
NADPHR-HSA-193965 (Reactome)
NADPHR-HSA-193981 (Reactome)
NADPHR-HSA-193995 (Reactome)
NADPHR-HSA-193997 (Reactome)
NADPHR-HSA-194017 (Reactome)
NADPHR-HSA-196060 (Reactome)
NADPHR-HSA-469659 (Reactome)
NADPHR-HSA-804969 (Reactome)
O2R-HSA-193054 (Reactome)
O2R-HSA-193060 (Reactome)
O2R-HSA-193065 (Reactome)
O2R-HSA-193068 (Reactome)
O2R-HSA-193070 (Reactome)
O2R-HSA-193072 (Reactome)
O2R-HSA-193099 (Reactome)
O2R-HSA-193101 (Reactome)
O2R-HSA-193143 (Reactome)
O2R-HSA-193964 (Reactome)
O2R-HSA-193965 (Reactome)
O2R-HSA-193981 (Reactome)
O2R-HSA-193995 (Reactome)
O2R-HSA-193997 (Reactome)
O2R-HSA-194017 (Reactome)
P4ArrowR-HSA-193052 (Reactome)
P4R-HSA-193072 (Reactome)
P4R-HSA-193964 (Reactome)
POMC(138-176)ArrowR-HSA-193064 (Reactome)
POMC(138-176)ArrowR-HSA-193070 (Reactome)
POMC(138-176)ArrowR-HSA-193073 (Reactome)
POMC(138-176)ArrowR-HSA-193997 (Reactome)
POMC(138-176)ArrowR-HSA-469659 (Reactome)
PREGArrowR-HSA-193097 (Reactome)
PREGArrowR-HSA-193101 (Reactome)
PREGR-HSA-193068 (Reactome)
PREGR-HSA-193097 (Reactome)
PREGR-HSA-196350 (Reactome)
R-HSA-193052 (Reactome) Pregn-5-ene-3,20-dione isomerizes to progesterone. This reaction is catalyzed by the isomerase activity of 3 beta-HSD, associated with the endoplasmic reticulum membrane. The active form of the enzyme is a homodimer. The enzyme occurs in two isoforms that are similar in their biochemical properties but differ in their tissue expression: type I (HSD3B1) is found in placenta and skin, while type II (HSD3B2) is found in the adrenal glands and gonads.
The hormone lutropin (LH) triggers ovulation and development of the corpus luteum, that in turn increases production of progesterone.
R-HSA-193054 (Reactome) Cholesterol and NADPH + H+ react to form 22beta-hydroxycholesterol, NADP+, and H2O, catalyzed by CYP11A (P450scc) associated with the inner mitochondrial membrane.
R-HSA-193060 (Reactome) The conversion of androstenedione (ANDST) to estrone (E1) is catalysed by aromatase (CYP19A1) associated with the endoplasmic reticulum membrane (Toda et al. 1990, Simpson et al. 1994).
R-HSA-193064 (Reactome) The 17HSD family of enzymes catalyze the final step in the synthesis of estradiol and testosterone. They convert inactive 17-ketosteroids to their active 17beta-hydroxy forms. Androstenedione, a ketosteroid, is reduced to testosterone, a highly potent androgen, by the enzyme 17beta-hydroxysteroid dehydrogenase isoform III (17HSD3). The other human isoforms of 17HSDs to take part in the final steps of active steroid biosynthesis are types 1 and VII, which reduce estrone to estradiol.
Corticotropin (Adrenocorticotropic hormone, ACTH) acts through the ACTH receptor called melanocortin receptor type 2 (MC2R) to stimulate steroidogenesis, increasing the production of androgens (McKenna et al, 1997).
In males, Lutropin (LH) stimulates testosterone production.
R-HSA-193065 (Reactome) 22beta-hydroxycholesterol, NADPH + H+, and O2 react to form 20alpha,22beta-hydroxycholesterol, NADP+ and H2O, catalyzed by CYP11A (P450scc) associated with the inner mitochondrial membrane.
R-HSA-193068 (Reactome) Pregnenolone (PREG) and NADPH + H+ react to form 17alpha-hydroxypregnenolone (17aHPREG), NADP+, and H2O. Steroid 17 alpha hydroxylase/17,20 lyase (CYP17A1), associated with the endoplasmic reticulum membrane, catalyzes this reaction.
R-HSA-193070 (Reactome) 17-alpha-hydroxypregnenolone, NADPH + H+, and O2 react to form DHA (dehydroepiandrostenedione), NADP+, H2O, and acetaldehyde. CYP17 (which also catalyzes 17-alpha-hydroxylation) catalyzes this lyase reaction. There are marked species differences in which substrate is used for this lyase activity. The human enzyme prefers 17alpha-pregnenolone (delta5 steroid) as substrate (Brock, BJ, Waterman, MR, 1999). Corticotropin (Adrenocorticotropic hormone, ACTH) acts through the ACTH receptor called melanocortin receptor type 2 (MC2R) to stimulate steroidogenesis, increasing the production of androgens (McKenna et al, 1997).
R-HSA-193072 (Reactome) Progesterone (P4), NADPH + H+, and O2 react to form 17alpha-hydroxyprogesterone (17aHPROG), NADP+, and H2O. This reaction is catalyzed by steroid 17 alpha hydroxylase/17,20 lyase (CYP17A1), associated with the endoplasmic reticulum membrane.
R-HSA-193073 (Reactome) In this two-step reaction catalyzed by 3beta-HSD associated with the endoplasmic reticulum membrane, the 3-hydroxyl group of DHA is oxidized to a keto group and the double bond in the steroid nucleus is then isomerized from the five to the 4 position. Corticotropin (Adrenocorticotropic hormone, ACTH) acts through the ACTH receptor called melanocortin receptor type 2 (MC2R) to stimulate steroidogenesis, increasing the production of androgens (McKenna et al, 1997).
R-HSA-193097 (Reactome) Inferred from rat: Pregenolone is translocated from the mitochondrial matrix to the cytosol. Neither transport proteins to mediate its movement across the inner mitochondrial membrane nor carrier proteins to facilitate its movement in the cytosol have been identified, and the mechanism of this translocation is unknown (Ray and Strott 1991).
R-HSA-193099 (Reactome) 17Alpha-hydroxyprogesterone (17aHPROG), NADPH + H+, and O2 react to form 4-Androstene-3, 17-dione (ANDST), NADP+, H2O, and acetaldehyde. Steroid 17 alpha hydroxylase/17,20 lyase (CYP17A1), which also catalyzes 17-alpha-hydroxylation, catalyzes this lyase reaction.
R-HSA-193101 (Reactome) 20alpha,22beta-hydroxycholesterol (20a,22b-DHCHOL), NADPH + H+, and O2 react to form pregnenolone (PREG), isocaproaldehyde (ISCAL), NADP+ and H2O. This cleavage reaction is catalysed by CYP11A (P450scc) associated with the inner mitochondrial membrane (Strushkevich et al. 2011). PREG is substantially more hydrophilic than cholesterol (CHOL) and hydroxycholesterol (HCHOL) and is released into the mitochondrial matrix.
R-HSA-193143 (Reactome) The conversion of testosterone to estradiol is catalyzed by aromatase (CYP19A1) associated with the endoplasmic reticulum membrane.
R-HSA-193961 (Reactome) Pregn-5-ene-3,20-dione-17-ol isomerizes to 17-hydroxyprogesterone. This reaction is catalyzed by the isomerase activity of 3 beta-HSD, associated with the endoplasmic reticulum membrane. The active form of the enzyme is a homodimer. The enzyme occurs in two isoforms that are similar in their biochemical properties but differ in their tissue expression: type I (HSD3B1) is found in placenta and skin, while type II (HSD3B2) is found in the adrenal glands and gonads.
R-HSA-193964 (Reactome) Progesterone, NAPDH + H+, and O2 react to form 11-deoxycorticosterone, NADP+ and H2O. This reaction is catalyzed by CYP21A2 associated with the endoplasmic reticulum membrane.
R-HSA-193965 (Reactome) 18-Hydroxycorticosterone and NADPH + H+ react to form aldosterone, NADP+, and H2O. This reaction is catalyzed by CYP11B2 associated with the inner mitochondrial membrane.
R-HSA-193981 (Reactome) 17-Hydroxyprogesterone, NADPH + H+, and O2 react to form 11-deoxycortisol, NADP+, and H2O. This reaction is catalyzed by CYP21A2 (steroid 21-hydroxylase) associated with the endoplasmic reticulum membrane.
R-HSA-193995 (Reactome) Corticosterone, NADPH + H+, and O2 react to form 18-hydroxycorticosterone, NADP+, and H2O. This reaction is catalyzed by CYP11B2 associated with the inner mitochondrial membrane.
R-HSA-193996 (Reactome) 11-deoxycorticosterone is synthesized in a reaction at the endoplasmic reticulum membrane and is further metabolized, ultimately to yield aldosterone, in reactions catalyzed by mitochondrial enzymes. The means by which 11-deoxycorticosterone translocates into the mitochondrial matrix, however, is unknown.
R-HSA-193997 (Reactome) Cytochrome P450 11B1, mitochondrial (CYP11B1) usually hydroxylates 11-deoxycortisol (11DCORT) to form cortisol (CORT). CYP11B1 is associated with the inner mitochondrial membrane. Corticotropin (Adrenocorticotropic hormone, ACTH) acts through the ACTH receptor, melanocortin receptor type 2 (MC2R) to stimulate steroidogenesis, increasing the production of androgens (McKenna et al, 1997).
R-HSA-194017 (Reactome) Cytochrome P450 11B2, mitochondrial (CYP11B2 aka aldosterone hydroxylase) is an enzyme necessary for aldosterone biosynthesis via corticosterone (CORST) and 18-hydroxycorticosterone (18HCORST). The 11-beta oxidation of 11-deoxycorticosterone (11DCORST) leads to corticosterone (CORST) and 18-hydroxylation of this leads to 18-hydroxycorticosterone (18HCORST). 18-oxidation of 18HCORST yields aldosterone.
R-HSA-194023 (Reactome) Cortisol and NADP+ react to form cortisone, NADPH, and H+. This reaction is catalyzed by 11beta-hydroxysteroid dehydrogenases 11B1 and B2 (HSD11B1, B2), associated with the endoplasmic reticulum membrane. The conversion of cortisol (CORT), an active hormone, into inactive cortisone (COR) occurs in many tissues in the body, notably in the liver, and appears to play a role in regulating cortisol activity (Tannin et al. 1991, Stewart et al. 1987).
R-HSA-194025 (Reactome) 11-deoxycortisol is synthesized in a reaction at the endoplasmic reticulum membrane and is further metabolized to cortisol in a reaction catalyzed by mitochondrial enzymes. The means by which 11-deoxycortisol translocates into the mitochondrial matrix, however, is unknown.
R-HSA-194036 (Reactome) Cortisol is translocated from the mitochondrial matrix into the cytosol by an unknown mechanism (Du et al. 2009).
R-HSA-196060 (Reactome) Isocaproaldehyde is reduced by NADPH + H+ to yield 4-methylpentan-1-ol and NADP+. This cytosolic reaction is catalyzed by AKR1B1 (aldose reductase). The purified human enzyme has been shown to catalyze this reaction efficiently in vitro; its abundance in adrenal tissue in humans and other mammals and its concordant expression with other enzymes of steroid hormone synthesis are consistent with it performing this role in vivo as well (Matsuura et al. 1996; Lefrancois-Martinez et al. 2004). The metabolic fate of 4-methylpentan-1-ol is unknown.
R-HSA-196086 (Reactome) Cholesterol is released from its complex with STAR in the mitochondrial intermembrane space. The mechanism of this process in vivo remains incompletely understood.
R-HSA-196125 (Reactome) Isocaproaldehyde (4-methylpentanal) is translocated from the mitochondrial matrix to the cytosol. The transporter that mediates this reaction is unknown. The reaction is inferred to exist because isocaproaldehyde is generated within the mitochondrion while the enzyme that reduces it to the corresponding alcohol is located in the cytosol (Matsuura et al. 1996).
R-HSA-196126 (Reactome) Cholesterol traverses the cytosol and the mitochondrial intermembrane space complexed with carrier proteins. This process is essential for the synthesis of steroid hormones in humans. Nevertheless, molecular details of the transport process remain incomplete. A plausible model, supported by studies in vitro and in cells overexpressing cloned human proteins, is that cytosolic StAR-related cholesterol-binding proteins STARD3, 4, and 6 bind cholesterol liberated from lysosomes or cytosolic lipid droplets and carry it to the outer mitochondrial membrane (Rodriguez-Aguado et al. 2005; Soccio et al. 2002). Here, it is transferred to the steroidogenic acute regulatory protein (STAR) and carried across the mitochondrial intermembrane space (Miller 2007, Letourneau et al. 2015).

Mutations in the gene encoding STAR block synthesis of all steroid hormones in humans, indicating the critical importance of this transport step in the biosynthetic process (Bose et al. 1996). The transport step is also a key site for normal regulation of steroid hormone synthesis, as STAR protein is unstable and its synthesis is up-regulated in response to signals such as the binding of ACTH to its receptors on adrenal cells (Stocco 2001).

R-HSA-196350 (Reactome) Pregnenolone and NAD+ react to form pregn-5-ene-3,20-dione and NADH + H+. This reaction is catalyzed by the 3 beta-hydroxysteroid activity of 3-beta-hydroxysteroid dehydrogenase/isomerase (HSD3B) enzyme associated with the endoplasmic reticulum membrane. The active form of the enzyme is a homodimer. The enzyme occurs in two isoforms that are similar in their biochemical properties but differ in their tissue expression: type I (HSD3B1) is found in placenta and skin, while type II (HSD3B2) is found in the adrenal glands and gonads.
R-HSA-196372 (Reactome) 17-Hydroxypregnenolone and NAD+ react to form pregn-5-ene-3,20-dione-17-ol and NADH + H+. This reaction is catalyzed by the 3 beta-hydroxysteroid activity of 3-beta-hydroxysteroid dehydrogenase/isomerase (HSD3B) enzyme associated with the endoplasmic reticulum membrane. The active form of the enzyme is a homodimer. The enzyme occurs in two isoforms that are similar in their biochemical properties but differ in their tissue expression: type I (HSD3B1) is found in placenta and skin, while type II (HSD3B2) is found in the adrenal glands and gonads.
R-HSA-469659 (Reactome) The conversion of testosterone to the most potent androgen, 5-alpha-dihydrotestosterone (DHT), is catalyzed by the microsomal 5alpha-steroid reductase enzymes, of which there are three reported types in humans to date (SRD5A1-3) (Andersson S and Russell DW, 1990; Andersson S et al, 1991; Uemura M et al, 2008 respectively). These enzymes are expressed in the prostate and other androgen target sites. Defects in SRD5A2 are the cause of pseudovaginal perineoscrotal hypospadias, also known as male pseudohermaphroditism (Anwar R et al, 1997). Corticotropin (Adrenocorticotropic hormone, ACTH) acts through the ACTH receptor called melanocortin receptor type 2 (MC2R) to stimulate steroidogenesis, increasing the production of androgens (McKenna et al, 1997).
R-HSA-5693390 (Reactome) Estradiol 17-beta-dehydrogenase 11 (HSD17B11) may participate in androgen metabolism during steroidogenesis where it dehydrogenates estradiol-17-beta (EST17b) to estrone (E1) (Chai et al. 2003).
R-HSA-5696822 (Reactome) The aldo-keto reductases (AKRs) are multifunctional enzymes that catalyse the reduction of biogenic and xenobiotic aldehydes and ketones as well as the synthesis and metabolism of sex hormones. The newest identified member, Aldo-keto reductase family 1 member B15 (AKR1B15) is able to catalyse the reduction of 17beta-sex hormones such as 17beta-estradiol (EST17b) to estrone (E1). Two isoforms of AKR1B15 exist in different subcellular locations; isoform 2 is cytosolic (like most AKRs) whereas isoform 1 co-localises with the mitochondria (Weber et al. 2015).
R-HSA-6810594 (Reactome) 17-beta-hydroxysteroid dehydrogenases are primarily involved in the metabolism of 17-hydroxysteroids and of other substrates such as fatty acids, prostaglandins and xenobiotics. The human DHRS10 gene encodes 17-beta-hydroxysteroid dehydrogenase 14 (HSD17B14) which in tetrameric form can oxidise estradiol (E2) to estrone (E1) in vitro (Lukacik et al. 2007). It shows highest expression in brain, liver and placenta and has been shown to act as a protective factor in breast cancer (Sivik et al. 2012).
R-HSA-804969 (Reactome) Expression of HSD17B1 which is the main enzyme that catalyzes the hydrogenation of estrone is strongly restricted to placenta, ovaries, endometrium and breast tissue (Moeller and Adamski, 2009).
R-HSA-8862137 (Reactome) Estradiol 17-beta-dehydrogenase 2 (HSD17B2) is a microsomal enzyme expressed in osteoblastic cells (Wu et al. 1993, Dong et al. 1998). It catalyses the oxidation of highly active beta-estradiol (E2) and testosterone into the weaker 17-ketosteroids estrone (E1) and androstene-3,17-dione, respectively. Osteoporosis is a common, age-related disease characterised by a systemic impairment of bone mass, increasing bone fragility and fracture risk. A drop in E2 and testosterone levels, occurring with ageing, is the main factor driving the onset and progression of this disease. Potent inhibitors of HSD17B2 could be a novel treatment for this disease (Gargano et al. 2015).
R-HSA-8951850 (Reactome) The 18 kDa translocator protein (TSPO), originally identified as a peripheral-type benzodiazepine receptor (BZRP), is a drug- and cholesterol-binding protein found at particularly high levels in steroid synthesising cells such as those of the adrenal glands and testes (Lin et al. 1993, De Souza et al. 1985). TSPO is localised to the outer mitochondrial membrane (Anholt et al. 1986) and could facilitate the transport of cholesterol (CHOL) to the inner mitochondrial membrane where the first step of steroidogenesis occurs (review - Papadopoulos et al. 2015). The peripheral-type benzodiazepine receptor-associated protein 1 (TSPOAP1, aka BZRAP1, PRAX1) is a cytosolic protein that specifically interacts with TSPO (Galiegue et al. 1993) but its role is undetermined.
SRD5A1-3mim-catalysisR-HSA-469659 (Reactome)
STAR:CHOLArrowR-HSA-196126 (Reactome)
STAR:CHOLR-HSA-196086 (Reactome)
STARArrowR-HSA-196086 (Reactome)
STARD3:STARD3NL, STARD4,6:CHOLR-HSA-196126 (Reactome)
STARD3:STARD3NL, STARD4,6ArrowR-HSA-196126 (Reactome)
STARR-HSA-196126 (Reactome)
TESTArrowR-HSA-193064 (Reactome)
TESTR-HSA-193143 (Reactome)
TESTR-HSA-469659 (Reactome)
TSPO:BZRAP1mim-catalysisR-HSA-8951850 (Reactome)
glyco-LutropinArrowR-HSA-193052 (Reactome)
glyco-LutropinArrowR-HSA-193064 (Reactome)
pregn-5-ene-3,20-dione-17-olArrowR-HSA-196372 (Reactome)
pregn-5-ene-3,20-dione-17-olR-HSA-193961 (Reactome)
pregn-5-ene-3,20-dioneArrowR-HSA-196350 (Reactome)
pregn-5-ene-3,20-dioneR-HSA-193052 (Reactome)
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