Glucocorticoid biosynthesis (Homo sapiens)

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Primary aldosteronismGlucocorticoid-remediable aldosteronism1, 2221-hydroxylase deficiency17alpha-HydroxyprogesteroneSRD5A15beta-pregnane-17alpha,20beta,21-triol-3,11-dione20beta-hydroxycortisolTetrahydrocortisol4-Pregnene-17alpha,20alpha-diol-3,11-dione18-hydroxycortisolCYP11B2 11-KetoetiocholanoloneSteroid hormone precursor biosynthesis20beta-DihydrocortisoneHSD11B2Tetrahydrocortisone5beta-pregnane-11beta,17alpha,20beta,21-tetrol-3-oneHSD11B111beta-Hydroxyetiocholanolone17alpha-hydroxy-5beta-Pregnane-3,11,20-trione20alpha-Hydroxycortisol5alpha-Tetrahydrocortisol21-deoxycortisolAKR1C4Cortisone5beta-pregnane-17alpha,20alpha,21-triol-3,11-dione18-oxo-dihydrocortisolCYP21A25beta-Pregnane-3alpha,17alpha-diol-11,20-dione5beta-dihydrocortisolAKR1D1CortisolSRD5A220alpha-Dihydrocortisone5beta-pregnane-11beta,17alpha,20alpha,21-tetrol-3-one18-oxo-cortisol5beta-pregnane3alpha,11beta,17alpha,20alpha-tetrol-21-oic acid5alpha-DihydrocortisolPregnanetriolone4,5beta-Dihydrocortisone21-Deoxycortisone5beta-Pregnane-17alpha,20alpha-diol-3,11-dioneAKR1C2CBR1CYP11B1AKR1C36beta-hydroxycortisolCYP3A418-oxo-tetrahydrocortisolAKR1C111-deoxycortisol5beta-pregnane-3alpha,11beta,17alpha,20beta-terol-21-oic acidalpha-cortolonebeta-cortoloneAKR1C4AKR1C2AKR1C3AKR1C1AKR1D1AKR1D1AKR1C4AKR1C2AKR1C3AKR1C1AKR1D1alpha-Cortolbeta-cortolAKR1C4AKR1C2AKR1C3AKR1C1CYP11B1HSD11B2HSD11B1CYP11B2AKR1D1AKR1D1AKR1D1


Description

Glucocorticoid biosynthesis; a very complex multistep process starting from cholesterol in the inner mitochondrial membrane through StAR and StAR-related proteins. Glucocorticoid metabolites are essential in immune system regulation through the glucocorticoid receptor. Most of these compounds are produces in the adrenal gland, however can also be produced in other tissues, e.g. skin, brain, intestine [PMID:32203088].


The pathway knowledge depicted in this model stems from William Griffths.

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Ontology Terms

 

Bibliography

  1. Radomir M Slominski, Robert C Tuckey, Pulak R Manna, Anton M Jetten, Arnold Postlethwaite, Chander Raman, Andrzej T Slominski; ''Extra-adrenal glucocorticoid biosynthesis: implications for autoimmune and inflammatory disorders''; Genes Immun., 2022 PubMed Europe PMC Scholia
  2. Schiffer L, Barnard L, Baranowski ES, Gilligan LC, Taylor AE, Arlt W, Shackleton CHL, Storbeck KH; ''Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: A comprehensive review.''; J Steroid Biochem Mol Biol, 2019 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
134506view11:40, 22 July 2024EweitzModified description
134504view11:37, 22 July 2024EweitzModified description
134503view11:36, 22 July 2024EweitzOntology Term : 'Conn's syndrome' added !
134502view11:35, 22 July 2024EweitzOntology Term : '21-alpha-hydroxylase deficiency pathway' added !
127387view19:58, 27 September 2023Conroy lipidsprotein to gene product for lipidmaps consistency
126881view15:07, 29 June 2023DeSlConnected unconnected line
126880view15:06, 29 June 2023DeSlAdded Rhea ID info in description
125685view11:09, 7 March 2023Conroy lipidsadd IDs to 21-oic acids and more 21-oics
125643view15:11, 6 March 2023Conroy lipidsadd some terminal products with unknown routes
125495view10:34, 20 February 2023LinaSchifferModified description
125450view14:26, 14 February 2023Conroy lipidscorrect typo
124376view09:15, 20 October 2022DeSlAdded a more elaborate description and lit. ref.
124375view09:09, 20 October 2022DeSlchanged width for all interactions missing a Rhea ID
124374view09:06, 20 October 2022DeSlAdded PW node
124371view08:52, 20 October 2022DeSlOntology Term : 'classic metabolic pathway' added !
124369view08:51, 20 October 2022DeSlOntology Term : 'cortisol biosynthetic pathway' added !
124053view09:56, 15 September 2022DeSlUpdated layut of DataNodes, connected unconnected interactions
124052view09:44, 15 September 2022DeSlConverted all GeneProducts to Protein DataNodes
124051view09:43, 15 September 2022DeSlAnnotated CYP21A1 with human ortholog (called CYP21A2).
124050view09:37, 15 September 2022DeSlOntology Term : 'glucocorticoid biosynthetic pathway' added !
123950view11:04, 7 September 2022Conroy lipids
123949view11:03, 7 September 2022Conroy lipids
123948view11:00, 7 September 2022Conroy lipidsfix link
123947view10:49, 7 September 2022Conroy lipidsmove annotations from catalysis to conversion
123913view13:12, 30 August 2022Conroy lipids
123912view13:12, 30 August 2022Conroy lipids
123911view13:11, 30 August 2022Conroy lipidsadd extra lipids and 2 disease pathway branches
123890view20:59, 24 August 2022Conroy lipidsOntology Term : 'lipid metabolic pathway' added !
123889view20:57, 24 August 2022Conroy lipidsNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
11-KetoetiocholanoloneMetaboliteLMST02020123 (LIPID MAPS)
11-deoxycortisolMetaboliteLMST02030086 (LIPID MAPS)
11beta-Hydroxy etiocholanoloneMetaboliteLMST02020086 (LIPID MAPS)
17alpha-HydroxyprogesteroneMetaboliteLMST02030161 (LIPID MAPS)
17alpha-hydroxy-5beta-Pregnane-3,11,20-trioneMetaboliteLMST02030291 (LIPID MAPS)
18-hydroxycortisolMetaboliteLMST02030295 (LIPID MAPS)
18-oxo-cortisolMetaboliteLMST02030296 (LIPID MAPS)
18-oxo-dihydrocortisolMetaboliteLMST02030297 (LIPID MAPS)
18-oxo-tetrahydrocortisolMetaboliteLMST02030298 (LIPID MAPS)
20alpha-DihydrocortisoneMetaboliteLMST02030265 (LIPID MAPS)
20alpha-HydroxycortisolMetaboliteLMST02030271 (LIPID MAPS)
20beta-DihydrocortisoneMetaboliteLMST02030266 (LIPID MAPS)
20beta-hydroxycortisolMetaboliteLMST02030270 (LIPID MAPS)
21-DeoxycortisoneMetaboliteLMST02030289 (LIPID MAPS)
21-deoxycortisolMetaboliteLMST02030195 (LIPID MAPS)
4,5beta-DihydrocortisoneMetaboliteLMST02030095 (LIPID MAPS)
4-Pregnene-17alpha,20alpha-diol-3,11-dioneMetaboliteLMST02030294 (LIPID MAPS)
5alpha-DihydrocortisolMetaboliteLMST02030272 (LIPID MAPS)
5alpha-TetrahydrocortisolMetaboliteLMST02030200 (LIPID MAPS)
5beta-Pregnane-17alpha,20alpha-diol-3,11-dioneMetaboliteLMST02030293 (LIPID MAPS)
5beta-Pregnane-3alpha,17alpha-diol-11,20-dioneMetaboliteLMST02030292 (LIPID MAPS)
5beta-dihydrocortisolMetaboliteLMST02030204 (LIPID MAPS)
5beta-pregnane 3alpha,11beta,17alpha,20alpha-tetrol-21-oic acidMetabolite
5beta-pregnane- 3alpha,11beta,17alpha,20beta-terol-21-oic acidMetabolite
5beta-pregnane-11beta,17alpha, 20alpha,21-tetrol-3-oneMetaboliteLMST02030273 (LIPID MAPS)
5beta-pregnane-11beta,17alpha,20beta,21-tetrol-3-oneMetaboliteLMST02030274 (LIPID MAPS)
5beta-pregnane-17alpha,20alpha,21-triol-3,11-dioneMetaboliteLMST02030267 (LIPID MAPS)
5beta-pregnane-17alpha,20beta,21-triol-3,11-dioneMetaboliteLMST02030268 (LIPID MAPS)
6beta-hydroxycortisolMetaboliteLMST02030269 (LIPID MAPS)
AKR1C1ProteinQ04828 (Uniprot-TrEMBL)
AKR1C2ProteinP52895 (Uniprot-TrEMBL)
AKR1C3ProteinP42330 (Uniprot-TrEMBL)
AKR1C4ProteinP17516 (Uniprot-TrEMBL)
AKR1D1ProteinP51857 (Uniprot-TrEMBL)
CBR1ProteinP16152 (Uniprot-TrEMBL)
CYP11B1ProteinP15538 (Uniprot-TrEMBL)
CYP11B2ProteinP19099 (Uniprot-TrEMBL)
CYP21A2ProteinP08686 (Uniprot-TrEMBL) According to UniProt, the original geneName (CYP21A1) is only found in Bovin, Rat, Mouse and Pig. NCBI gene lists a Human ortholog, called: CYP21A2. This is linked to a UniProt entry, which details the reactions this protein catalyzes: " Catalyzes the hydroxylation at C-21 of progesterone and 17alpha-hydroxyprogesterone to respectively form 11-deoxycorticosterone and 11-deoxycortisol, intermediate metabolites in the biosynthetic pathway of mineralocorticoids and glucocorticoids (PubMed:25855791, PubMed:10602386, PubMed:16984992, PubMed:22014889, PubMed:27721825)." Source: [https://www.uniprot.org/uniprotkb/P08686/entry]. This information is also reflected in Rhea.
CYP3A4ProteinP08684 (Uniprot-TrEMBL)
CortisolMetaboliteLMST02030001 (LIPID MAPS)
CortisoneMetaboliteLMST02030090 (LIPID MAPS)
HSD11B1ProteinP28845 (Uniprot-TrEMBL)
HSD11B2ProteinP80365 (Uniprot-TrEMBL)
PregnanetrioloneMetaboliteLMST02030290 (LIPID MAPS)
SRD5A1ProteinP18405 (Uniprot-TrEMBL)
SRD5A2ProteinP31213 (Uniprot-TrEMBL)
Steroid hormone precursor biosynthesisPathwayWP5277 (WikiPathways)
TetrahydrocortisolMetaboliteLMST02030143 (LIPID MAPS)
TetrahydrocortisoneMetaboliteLMST02030098 (LIPID MAPS)
alpha-CortolMetaboliteLMST02030228 (LIPID MAPS)
alpha-cortoloneMetaboliteLMST02030227 (LIPID MAPS)
beta-cortolMetaboliteLMST02030229 (LIPID MAPS)
beta-cortoloneMetaboliteLMST02030230 (LIPID MAPS)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
11-deoxycortisolCortisolmim-conversion46101 (Rhea)
17alpha-Hydroxyprogesterone11-deoxycortisolmim-conversion50309 (Rhea) EC: 1.14.14.16
Cortisol20beta-hydroxycortisolmim-conversion70216 (Rhea) EC:1.1.1.184
Cortisol5beta-dihydrocortisolmim-conversion46645 (Rhea) EC:1.3.1.3
Cortisol6beta-hydroxycortisolmim-conversion55829 (Rhea) EC:1.14.14.1
CortisolCortisonemim-conversion68618 (Rhea) EC: 1.1.1.146
Cortisone4,5beta-Dihydrocortisonemim-conversion14039 (Rhea) EC:1.3.1.3
CortisoneCortisolmim-conversion68617 (Rhea)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5280"
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