Alternative pathway of fetal androgen synthesis (Homo sapiens)
From WikiPathways
Description
Next to the classical pathway of androgen synthesis (see [1]), alternative pathways are known, which make use of either selective expression patterns of isoenzymes or alternate enzymes. As an alternative, a socalled 'backdoor pathway', which can create dihydrotestosterone (DHT), skipping testosterone. Several enzymes between the classical and backdoor pathway are shared, however the later one utilises one unique enzyme, 3-alpha hydroxysteroid dehydrogenase 3 (gene: AKR1C2). Even though the relevance of this backdoor pathway for humans is not completely clear yet, mutations in the human AKR1C2 gene can lead to disordered sexual differentiation. This finding would indicate that both the classical and the alternative pathway are needed for normal development of male genitalia in humans.
For more information on androgens, see Hiort (2013 [2]), and for more information on the disease linked to this pathway, please visit Chapter 37 of the book of Blau (ISBN 3642403360 (978-3642403361)).Quality Tags
Ontology Terms
Bibliography
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History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
17-Hydroxyallopregnanolone | Metabolite | CHEBI:11909 (ChEBI) | |
17-Hydroxypregnenolone | Metabolite | Q2064889 (Wikidata) | |
17-Hydroxyprogesterone | Metabolite | HMDB0000374 (HMDB) | |
17-beta-HSD3 | GeneProduct | ENSG00000130948 (Ensembl) | |
17-beta-HSD | GeneProduct | ENSG00000130948 (Ensembl) | |
17-hydroxydihydroprogesterone | Metabolite | CHEBI:36723 (ChEBI) | |
3 HSD | Protein | P26439 (Uniprot-TrEMBL) | Aka HSD3B2; 3 beta-hydroxysteroid dehydrogenase type II |
3-beta-HSD | GeneProduct | ENSG00000203859 (Ensembl) | |
5-alpha-reductase 1 | GeneProduct | ENSG00000277893 (Ensembl) | |
5-alpha-reductase 2 | Protein | P31213 (Uniprot-TrEMBL) | |
AKR1C2/4 | GeneProduct | ENSG00000151632 (Ensembl) | |
AKR1C2 | Protein | P52895 (Uniprot-TrEMBL) | Responsible protein found through Rhea (not part of Blau book) |
AKR1C4 | GeneProduct | ENSG00000198610 (Ensembl) | |
Androstanediol | Metabolite | CHEBI:27727 (ChEBI) | |
Androstanedione | Metabolite | CHEBI:15994 (ChEBI) | |
Androstenedione | Metabolite | CHEBI:16422 (ChEBI) | |
Androsterone | Metabolite | CHEBI:16032 (ChEBI) | |
Cholesterol | Metabolite | CHEBI:16113 (ChEBI) | |
Cytb5 | Protein | P00167 (Uniprot-TrEMBL) | |
DHEA | Metabolite | CHEBI:28689 (ChEBI) | |
Dihydrotestosterone (DHT) | Metabolite | CHEBI:16330 (ChEBI) | |
NAD+ | Metabolite | CHEBI:57540 (ChEBI) | |
NADH | Metabolite | CHEBI:57945 (ChEBI) | |
NADP+ | Metabolite | CHEBI:58349 (ChEBI) | |
NADPH | Metabolite | CHEBI:57783 (ChEBI) | |
P450c17 | Protein | ENSG00000148795 (Ensembl) | |
P450c17 | Protein | P05093 (Uniprot-TrEMBL) | Function:"Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty" [https://www.uniprot.org/uniprot/P05093] |
P450scc | GeneProduct | ENSG00000140459 (Ensembl) | |
POR | Protein | P16435 (Uniprot-TrEMBL) | Function:"This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes" [https://www.uniprot.org/uniprot/P16435] |
Pregnenolone | Metabolite | CHEBI:16581 (ChEBI) | |
Progesterone | Metabolite | CHEBI:17026 (ChEBI) | |
RODH | Protein | O14756 (Uniprot-TrEMBL) | |
STAR | GeneProduct | ENSG00000147465 (Ensembl) | |
Testosterone | Metabolite | CHEBI:17347 (ChEBI) | |
androst-4-ene- 3,17-dione | Metabolite | CHEBI:16422 (ChEBI) |
Annotated Interactions
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Source | Target | Type | Database reference | Comment |
---|---|---|---|---|
17-Hydroxypregnenolone | 17-Hydroxyprogesterone | mim-conversion | 24077 (Rhea) | Specific Rhea for this reaction is not available at the moment; added Rhea for compounds classes reaction |
17-Hydroxypregnenolone | DHEA | mim-conversion | 50245 (Rhea) | |
17-Hydroxyprogesterone | Androstenedione | mim-conversion | 14754 (Rhea) | |
Androstanedione | Dihydrotestosterone (DHT) | mim-conversion | 41993 (Rhea) | |
Androstanedione | Dihydrotestosterone (DHT) | mim-conversion | 42121 (Rhea) | |
Androstenedione | Testosterone | mim-conversion | 14983 (Rhea) | |
Androstenedione | mim-conversion | 50817 (Rhea) | ||
Androsterone | Androstanedione | mim-conversion | 20378 (Rhea) | |
Androsterone | Androstanedione | mim-conversion | 20382 (Rhea) | |
Cholesterol | Pregnenolone | mim-conversion | 35740 (Rhea) | |
NAD+ | mim-conversion | 20382 (Rhea) | ||
NAD+ | mim-conversion | 41993 (Rhea) | ||
NADH | mim-conversion | 20382 (Rhea) | ||
NADH | mim-conversion | 41993 (Rhea) | ||
NADP+ | mim-conversion | 20378 (Rhea) | ||
NADP+ | mim-conversion | 42121 (Rhea) | ||
NADPH | mim-conversion | 20378 (Rhea) | ||
NADPH | mim-conversion | 42121 (Rhea) | ||
P450c17 | P450c17 | mim-modification | 24041 (Rhea) | |
Pregnenolone | 17-Hydroxypregnenolone | mim-conversion | 50237 (Rhea) | |
Pregnenolone | Progesterone | mim-conversion | 24077 (Rhea) | |
Progesterone | 17-Hydroxyprogesterone | mim-conversion | 46309 (Rhea) | |
Progesterone | androst-4-ene- 3,17-dione | mim-conversion | 14754 (Rhea) | |
Testosterone | Dihydrotestosterone (DHT) | mim-conversion | 50822 (Rhea) |