Classical pathway of steroidogenesis, including diseases (Homo sapiens)

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41251991153Lipoid adrenal hyperplasia83-beta-HSDDihydrotestosteroneOestradiolP450c21P450c17Corticosterone Methyl Oxidase IIP450scc11-DeoxycortisolProgesterone11beta-HSD1Corticosterone Methyl Oxidase I18-hydroxycorticosterone11-HSD2Deoxycorticosterone5-alpha-Reductase217-HydroxyprogesteroneSTARPORCorticosteronePregnenoloneCortisoneDHEA17-HydroxypregnenoloneAndrostenedionePORCholesterol17-beta-HSD3Cytochrome b5AldosteroneP450AroH6PDTestosteroneCortisolPOR3-beta-HSDP450c11P450c17P450c173-beta-HSDCholesterol side-chain cleavage deficiency717-Alpha-hydroxylase / 17-lyase deficiency3-beta-HSD type II deficiency161821-Hydroxylase deficiency2311-beta-hydroxylase type I deficiencyCorticosterone methyl oxidase deficiency14Cortisone reductase deficiency1012Apparent mineralocorticoid excess17-beta-HSD deficiency205-alpha-reductase type II deficiency17Aromatase deficiency2113P450 oxidoreductase deficiency3-beta-HSD type II deficiency2218PORProgesterone resistance6Oestrogen resistance15


Description

The biosynthesis of steroid hormones is a difficult process in which Cholesterol is transformed into mineralocorticoids, glucocorticoids and sex hormones via a series of hydroxylation, oxidation and reduction steps. To better understand the molecular level of sexual organ maturation in humans, the classical pathway and the alternative pathway of this process are produced. The pathways produce the main steroid hormones in humans, namely Progestogen, Corticosteroids, Androgens and Estrogens.

The classical pathway is meant to produce an important steroid called Androgen, which is a synthetic steroid hormone that regulates sexual development and the maintenance of the male sex organs via binding to androgen receptors.

For more information and details about Androgens and the diseases linked with this molecular pathway, please visit Chapter 37 of the book of Blau (ISBN 978-3-642-40337-8)

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Bibliography

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  2. Parsa AA, New MI; ''Steroid 21-hydroxylase deficiency in congenital adrenal hyperplasia.''; J Steroid Biochem Mol Biol, 2017 PubMed Europe PMC
  3. Mindnich R, Haller F, Halbach F, Moeller G, Hrabé de Angelis M, Adamski J; ''Androgen metabolism via 17beta-hydroxysteroid dehydrogenase type 3 in mammalian and non-mammalian vertebrates: comparison of the human and the zebrafish enzyme.''; J Mol Endocrinol, 2005 PubMed Europe PMC
  4. Yong AB, Montalto J, Pitt J, Oakes S, Preston T, Buchanan C; ''Corticosterone methyl oxidase type II (CMO II) deficiency: biochemical approach to diagnosis.''; Clin Biochem, 1994 PubMed Europe PMC
  5. Patel BG, Rudnicki M, Yu J, Shu Y, Taylor RN; ''Progesterone resistance in endometriosis: origins, consequences and interventions.''; Acta Obstet Gynecol Scand, 2017 PubMed Europe PMC
  6. Strushkevich N, MacKenzie F, Cherkesova T, Grabovec I, Usanov S, Park HW; ''Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system.''; Proc Natl Acad Sci U S A, 2011 PubMed Europe PMC
  7. Kuribayashi I, Nomoto S, Massa G, Oostdijk W, Wit JM, Wolffenbuttel BH, Shizuta Y, Honke K; ''Steroid 11-beta-hydroxylase deficiency caused by compound heterozygosity for a novel mutation, p.G314R, in one CYP11B1 allele, and a chimeric CYP11B2/CYP11B1 in the other allele.''; Horm Res, 2005 PubMed Europe PMC
  8. Palmisano BT, Zhu L, Stafford JM; ''Role of Estrogens in the Regulation of Liver Lipid Metabolism.''; Adv Exp Med Biol, 2017 PubMed Europe PMC
  9. Baquedano MS, Ciaccio M, Marino R, Perez Garrido N, Ramirez P, Maceiras M, Turjanski A, Defelipe LA, Rivarola MA, Belgorosky A; ''A novel missense mutation in the HSD3B2 gene, underlying nonsalt-wasting congenital adrenal hyperplasia. new insight into the structure-function relationships of 3β-hydroxysteroid dehidrogenase type II.''; J Clin Endocrinol Metab, 2015 PubMed Europe PMC
  10. Blau, Nenad, Duran, Marinus, Gibson, K, Michael, Dionisi-Vici, Carlo; ''Physician's Guidee to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Disease'''; ISBN 978-3-64240337-8, 2014
  11. Katsumata N; ''Cholesterol Side-Chain Cleavage Enzyme (SCC) Deficiency.''; Clin Pediatr Endocrinol, 2007 PubMed Europe PMC
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  14. Lawson AJ, Walker EA, Lavery GG, Bujalska IJ, Hughes B, Arlt W, Stewart PM, Ride JP; ''Cortisone-reductase deficiency associated with heterozygous mutations in 11beta-hydroxysteroid dehydrogenase type 1.''; Proc Natl Acad Sci U S A, 2011 PubMed Europe PMC
  15. Unal E, TaÅŸ FF, Demir V, Onay H, Haspolat YK; ''Aromatase Deficiency due to a Novel Mutation inCYP19A1Gene''; J Clin Res Pediatr Endocrinol, 2018 PubMed Europe PMC
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History

View all...
CompareRevisionActionTimeUserComment
108086view11:53, 28 November 2019FehrhartOntology Term : 'disease pathway' added !
104251view12:05, 12 May 2019EgonwRemoved the RHEA: prefix from the identifier.
104033view17:45, 25 April 2019IreneHemelModified description
103565view09:57, 15 March 2019ElineSandersChanged geneproducts into proteins
103497view14:17, 6 March 2019DeSlModified description
103496view14:14, 6 March 2019DeSlRemoved weird signs in lit. ref (second try).
103402view09:45, 27 February 2019DeSlRemoved weird signs in lit. ref; changed long OMIM links to short ones.
103345view12:55, 22 February 2019DeSlConnected unconnected line to P450c17
103344view12:54, 22 February 2019DeSlUpdated OMIM for Aromatase deficiency (was linked to gene iso disease before).
103343view12:51, 22 February 2019DeSlOntology Term : 'pseudohermaphroditism' added !
103342view12:47, 22 February 2019DeSlOntology Term : 'congenital adrenal hyperplasia' added !
103341view12:45, 22 February 2019DeSlOntology Term : 'congenital adrenal hyperplasia pathway' added !
103340view12:44, 22 February 2019DeSlOntology Term : 'apparent mineralocorticoid excess syndrome pathway' added !
103339view12:43, 22 February 2019DeSlOntology Term : 'lipoid congenital adrenal hyperplasia pathway' added !
103338view12:43, 22 February 2019DeSlOntology Term : 'congenital adrenal insufficiency' added !
103337view12:42, 22 February 2019DeSlChanged Omim for Cholesterol side-chain cleavage deficiency to correct one (previous OMIM was for gene, not for disease).
103336view12:36, 22 February 2019DeSlOntology Term : 'apparent mineralocorticoid excess syndrome' added !
103335view12:36, 22 February 2019DeSlOntology Term : 'apparent mineralocorticoid excess' added !
103334view12:36, 22 February 2019DeSlOntology Term : 'cortisone reductase deficiency' added !
103320view10:38, 22 February 2019ElineSanderschanged label
103318view10:04, 22 February 2019ElineSandersAdded Rhea identifiers to reactions and changed the H6PD conversion. Also changed some CheBI identifiers which were in the secondary form according to Jenskin
103290view15:38, 21 February 2019ElineSanders
103268view10:56, 20 February 2019ElineSandersnew annotation for some metabolites
103267view10:19, 20 February 2019ElineSanderschanged CMO lines and added Rhea
103248view10:31, 18 February 2019ElineSandersOntology Term : 'C19-steroid hormone biosynthetic pathway' added !
103247view10:30, 18 February 2019ElineSandersOntology Term : 'steroid biosynthetic pathway' added !
103244view10:13, 18 February 2019ElineSandersannotation to H6PD
103242view09:51, 18 February 2019ElineSandersModified description
103238view09:12, 18 February 2019ElineSandersAdded some diseases, rhea to cortisol reaction and pathway reference
103217view15:18, 17 February 2019DeSlChanged arrows for diseases to graphical lines; small layout changes.
103196view15:36, 15 February 2019IngebudeIdentified Cyt 5b
103175view14:48, 15 February 2019ElineSandersI added references to the diseases and some Rhea's to the catalysation reactions
103153view13:05, 15 February 2019ElineSandersModified description
103152view13:04, 15 February 2019ElineSandersModified title
103151view13:03, 15 February 2019ElineSandersModified title
103150view13:02, 15 February 2019ElineSandersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
11-DeoxycortisolMetaboliteCHEBI:28324 (ChEBI)
11-HSD2GeneProductENSG00000176387 (Ensembl)
11beta-HSD1GeneProductENSG00000117594 (Ensembl)
17-HydroxypregnenoloneMetaboliteQ2064889 (Wikidata)
17-HydroxyprogesteroneMetaboliteHMDB00374 (HMDB)
17-beta-HSD3GeneProductENSG00000130948 (Ensembl)
18-hydroxycorticosteroneMetaboliteCHEBI:16485 (ChEBI)
3-beta-HSDGeneProductENSG00000203859 (Ensembl)
5-alpha-Reductase2GeneProductENSG00000277893 (Ensembl)
AldosteroneMetaboliteCHEBI:2563 (ChEBI)
AndrostenedioneMetaboliteCHEBI:2709 (ChEBI)
CholesterolMetaboliteCHEBI:3659 (ChEBI)
Corticosterone Methyl Oxidase IGeneProductENSG00000179142 (Ensembl)
Corticosterone Methyl Oxidase IIGeneProductENSG00000179142 (Ensembl)
CorticosteroneMetaboliteCHEBI:16827 (ChEBI)
CortisolMetaboliteCHEBI:3893 (ChEBI)
CortisoneMetaboliteCHEBI:3896 (ChEBI)
Cytochrome b5ProteinJ3KNC7 (Uniprot-TrEMBL)
DHEAMetaboliteCHEBI:1723 (ChEBI)
DeoxycorticosteroneMetaboliteHMDB00016 (HMDB)
DihydrotestosteroneMetaboliteCHEBI:41876 (ChEBI)
H6PDGeneProductENSG00000049239 (Ensembl)
OestradiolMetaboliteCHEBI:16469 (ChEBI)
P450AroGeneProductENSG00000137869 (Ensembl)
P450c11GeneProductENSG00000160882 (Ensembl)
P450c17GeneProductENSG00000148795 (Ensembl)
P450c21GeneProductENSG00000231852 (Ensembl)
P450sccGeneProductENSG00000140459 (Ensembl)
  • also known as CYP11A1
  • Type your comment here
PORProteinP16435 (Uniprot-TrEMBL)
PregnenoloneMetaboliteCHEBI:16581 (ChEBI)
ProgesteroneMetaboliteCHEBI:8453 (ChEBI)
STARGeneProductENSG00000147465 (Ensembl)
TestosteroneMetaboliteCHEBI:9461 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
11-DeoxycortisolCortisolmim-conversionRHEA:15630 (Rhea)
AndrostenedioneTestosteronemim-conversionRHEA:14983 (Rhea)
Corticosterone18-hydroxycorticosteronemim-conversionRHEA:11873 (Rhea)
CortisolCortisonemim-conversionRHEA:53117 (Rhea)
CortisoneCortisolmim-conversionRHEA:11390 (Rhea)
DeoxycorticosteroneCorticosteronemim-conversionRHEA:15630 (Rhea)
PregnenoloneProgesteronemim-conversionRHEA:43929 (Rhea)
TestosteroneDihydrotestosteronemim-conversionRHEA:54385 (Rhea)
TestosteroneOestradiolmim-conversionRHEA:38192 (Rhea)
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