Glucocorticoid biosynthesis (WP5280)
Homo sapiens
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 Griffiths. Metabolic reactions currently without a Rhea ID have been added in bold to the pathway model.
Authors
Conroy lipids , Denise Slenter , Lina Schiffer , and Eric WeitzActivity
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
cortisol biosynthetic pathway glucocorticoid biosynthetic pathway classic metabolic pathway 21-alpha-hydroxylase deficiency pathway lipid metabolic pathwayDisease Ontology
Conn's syndrome| Label | Type | Compact URI | Comment |
|---|---|---|---|
| 11-Ketoetiocholanolone | Metabolite | lipidmaps:LMST02020123 | |
| Tetrahydrocortisol | Metabolite | lipidmaps:LMST02030143 | |
| beta-cortolonic acid | Metabolite | lipidmaps:LMST02030301 | |
| 18-oxo-tetrahydrocortisol | Metabolite | lipidmaps:LMST02030298 | |
| 4-Pregnene-17alpha,20alpha-diol-3,11-dione | Metabolite | lipidmaps:LMST02030294 | |
| 17alpha-hydroxy-5beta-Pregnane-3,11,20-trione | Metabolite | lipidmaps:LMST02030291 | |
| Cortisol | Metabolite | lipidmaps:LMST02030001 | |
| 11beta-Hydroxyetiocholanolone | Metabolite | lipidmaps:LMST02020086 | |
| 5beta-pregnane-11beta,17alpha,20alpha,21-tetrol-3-one | Metabolite | lipidmaps:LMST02030273 | |
| 11-deoxycortisol | Metabolite | lipidmaps:LMST02030086 | |
| 5alpha-Tetrahydrocortisol | Metabolite | lipidmaps:LMST02030200 | |
| 5beta-pregnane-11beta,17alpha,20beta,21-tetrol-3-one | Metabolite | lipidmaps:LMST02030274 | |
| 21-deoxycortisol | Metabolite | lipidmaps:LMST02030195 | |
| 5alpha-Dihydrocortisol | Metabolite | lipidmaps:LMST02030272 | |
| 21-Deoxycortisone | Metabolite | lipidmaps:LMST02030289 | |
| 5beta-Pregnane-3alpha,17alpha-diol-11,20-dione | Metabolite | lipidmaps:LMST02030292 | |
| Cortolic acid | Metabolite | lipidmaps:LMST02030302 | |
| 17alpha-Hydroxyprogesterone | Metabolite | lipidmaps:LMST02030161 | |
| 5beta-pregnane-17alpha,20alpha,21-triol-3,11-dione | Metabolite | lipidmaps:LMST02030267 | |
| Pregnanetriolone | Metabolite | lipidmaps:LMST02030290 | |
| Cortolonic acid | Metabolite | lipidmaps:LMST02030300 | |
| 5beta-dihydrocortisol | Metabolite | lipidmaps:LMST02030204 | |
| 4,5beta-Dihydrocortisone | Metabolite | lipidmaps:LMST02030095 | |
| 5beta-pregnane-17alpha,20beta,21-triol-3,11-dione | Metabolite | lipidmaps:LMST02030268 | |
| 5beta-Pregnane-17alpha,20alpha-diol-3,11-dione | Metabolite | lipidmaps:LMST02030293 | |
| Cortisone | Metabolite | lipidmaps:LMST02030090 | |
| 20beta-hydroxycortisol | Metabolite | lipidmaps:LMST02030270 | |
| 20beta-Dihydrocortisone | Metabolite | lipidmaps:LMST02030266 | |
| 20alpha-Dihydrocortisone | Metabolite | lipidmaps:LMST02030265 | |
| 18-oxo-dihydrocortisol | Metabolite | lipidmaps:LMST02030297 | |
| Tetrahydrocortisone | Metabolite | lipidmaps:LMST02030098 | |
| beta-cortolic acid | Metabolite | lipidmaps:LMST02030303 | |
| 18-hydroxycortisol | Metabolite | lipidmaps:LMST02030295 | |
| 18-oxo-cortisol | Metabolite | lipidmaps:LMST02030296 | |
| 6beta-hydroxycortisol | Metabolite | lipidmaps:LMST02030269 | |
| 20alpha-Hydroxycortisol | Metabolite | lipidmaps:LMST02030271 | |
| alpha-cortolone | Metabolite | lipidmaps:LMST02030227 | |
| beta-cortolone | Metabolite | lipidmaps:LMST02030230 | |
| alpha-Cortol | Metabolite | lipidmaps:LMST02030228 | |
| beta-cortol | Metabolite | lipidmaps:LMST02030229 | |
| AKR1C4 | GeneProduct | uniprot:P17516 | |
| CYP11B2 | GeneProduct | uniprot:P19099 | |
| CYP21A2 | GeneProduct | uniprot:P08686 | 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. |
| AKR1C2 | GeneProduct | uniprot:P52895 | |
| HSD11B2 | GeneProduct | uniprot:P80365 | |
| CYP11B1 | GeneProduct | uniprot:P15538 | |
| HSD11B1 | GeneProduct | uniprot:P28845 | |
| CYP3A4 | GeneProduct | uniprot:P08684 | |
| SRD5A2 | GeneProduct | uniprot:P31213 | |
| CBR1 | GeneProduct | uniprot:P16152 | |
| SRD5A1 | GeneProduct | uniprot:P18405 | |
| AKR1C3 | GeneProduct | uniprot:P42330 | |
| AKR1D1 | GeneProduct | uniprot:P51857 | |
| AKR1C1 | GeneProduct | uniprot:Q04828 |
References
- Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: A comprehensive review. Schiffer L, Barnard L, Baranowski ES, Gilligan LC, Taylor AE, Arlt W, et al. J Steroid Biochem Mol Biol. 2019 Nov;194:105439. PubMed Europe PMC Scholia
- Extra-adrenal glucocorticoid biosynthesis: implications for autoimmune and inflammatory disorders. Slominski RM, Tuckey RC, Manna PR, Jetten AM, Postlethwaite A, Raman C, et al. Genes Immun. 2020 May;21(3):150–68. PubMed Europe PMC Scholia