Glucocorticoid biosynthesis (Homo sapiens)
From WikiPathways
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 Griffiths.
Metabolic reactions currently without a Rhea ID have been added in bold to the pathway model.
Quality Tags
Ontology Terms
Bibliography
- 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
- 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
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
11-Ketoetiocholanolone | Metabolite | LMST02020123 (LIPID MAPS) | |
11-deoxycortisol | Metabolite | LMST02030086 (LIPID MAPS) | |
11beta-Hydroxy etiocholanolone | Metabolite | LMST02020086 (LIPID MAPS) | |
17alpha-Hydroxyprogesterone | Metabolite | LMST02030161 (LIPID MAPS) | |
17alpha-hydroxy-5beta-Pregnane-3,11,20-trione | Metabolite | LMST02030291 (LIPID MAPS) | |
18-hydroxycortisol | Metabolite | LMST02030295 (LIPID MAPS) | |
18-oxo-cortisol | Metabolite | LMST02030296 (LIPID MAPS) | |
18-oxo-dihydrocortisol | Metabolite | LMST02030297 (LIPID MAPS) | |
18-oxo-tetrahydrocortisol | Metabolite | LMST02030298 (LIPID MAPS) | |
20alpha-Dihydrocortisone | Metabolite | LMST02030265 (LIPID MAPS) | |
20alpha-Hydroxycortisol | Metabolite | LMST02030271 (LIPID MAPS) | |
20beta-Dihydrocortisone | Metabolite | LMST02030266 (LIPID MAPS) | |
20beta-hydroxycortisol | Metabolite | LMST02030270 (LIPID MAPS) | |
21-Deoxycortisone | Metabolite | LMST02030289 (LIPID MAPS) | |
21-deoxycortisol | Metabolite | LMST02030195 (LIPID MAPS) | |
4,5beta-Dihydrocortisone | Metabolite | LMST02030095 (LIPID MAPS) | |
4-Pregnene-17alpha,20alpha-diol-3,11-dione | Metabolite | LMST02030294 (LIPID MAPS) | |
5alpha-Dihydrocortisol | Metabolite | LMST02030272 (LIPID MAPS) | |
5alpha-Tetrahydrocortisol | Metabolite | LMST02030200 (LIPID MAPS) | |
5beta-Pregnane-17alpha,20alpha-diol-3,11-dione | Metabolite | LMST02030293 (LIPID MAPS) | |
5beta-Pregnane-3alpha,17alpha-diol-11,20-dione | Metabolite | LMST02030292 (LIPID MAPS) | |
5beta-dihydrocortisol | Metabolite | LMST02030204 (LIPID MAPS) | |
5beta-pregnane-11beta,17alpha, 20alpha,21-tetrol-3-one | Metabolite | LMST02030273 (LIPID MAPS) | |
5beta-pregnane-11beta,17alpha,20beta,21-tetrol-3-one | Metabolite | LMST02030274 (LIPID MAPS) | |
5beta-pregnane-17alpha,20alpha,21-triol-3,11-dione | Metabolite | LMST02030267 (LIPID MAPS) | |
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione | Metabolite | LMST02030268 (LIPID MAPS) | |
6beta-hydroxycortisol | Metabolite | LMST02030269 (LIPID MAPS) | |
AKR1C1 | GeneProduct | Q04828 (Uniprot-TrEMBL) | |
AKR1C2 | GeneProduct | P52895 (Uniprot-TrEMBL) | |
AKR1C3 | GeneProduct | P42330 (Uniprot-TrEMBL) | |
AKR1C4 | GeneProduct | P17516 (Uniprot-TrEMBL) | |
AKR1D1 | GeneProduct | P51857 (Uniprot-TrEMBL) | |
CBR1 | GeneProduct | P16152 (Uniprot-TrEMBL) | |
CYP11B1 | GeneProduct | P15538 (Uniprot-TrEMBL) | |
CYP11B2 | GeneProduct | P19099 (Uniprot-TrEMBL) | |
CYP21A2 | GeneProduct | P08686 (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. |
CYP3A4 | GeneProduct | P08684 (Uniprot-TrEMBL) | |
Cortisol | Metabolite | LMST02030001 (LIPID MAPS) | |
Cortisone | Metabolite | LMST02030090 (LIPID MAPS) | |
Cortolic acid | Metabolite | LMST02030302 (LIPID MAPS) | |
Cortolonic acid | Metabolite | LMST02030300 (LIPID MAPS) | |
HSD11B1 | GeneProduct | P28845 (Uniprot-TrEMBL) | |
HSD11B2 | GeneProduct | P80365 (Uniprot-TrEMBL) | |
Pregnanetriolone | Metabolite | LMST02030290 (LIPID MAPS) | |
SRD5A1 | GeneProduct | P18405 (Uniprot-TrEMBL) | |
SRD5A2 | GeneProduct | P31213 (Uniprot-TrEMBL) | |
Steroid hormone precursor biosynthesis | Pathway | WP5277 (WikiPathways) | |
Tetrahydrocortisol | Metabolite | LMST02030143 (LIPID MAPS) | |
Tetrahydrocortisone | Metabolite | LMST02030098 (LIPID MAPS) | |
alpha-Cortol | Metabolite | LMST02030228 (LIPID MAPS) | |
alpha-cortolone | Metabolite | LMST02030227 (LIPID MAPS) | |
beta-cortol | Metabolite | LMST02030229 (LIPID MAPS) | |
beta-cortolic acid | Metabolite | LMST02030303 (LIPID MAPS) | |
beta-cortolone | Metabolite | LMST02030230 (LIPID MAPS) | |
beta-cortolonic acid | Metabolite | LMST02030301 (LIPID MAPS) |
Annotated Interactions
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Source | Target | Type | Database reference | Comment |
---|---|---|---|---|
11-deoxycortisol | Cortisol | mim-conversion | 46101 (Rhea) | |
17alpha-Hydroxyprogesterone | 11-deoxycortisol | mim-conversion | 50309 (Rhea) | EC: 1.14.14.16 |
Cortisol | 20beta-hydroxycortisol | mim-conversion | 70216 (Rhea) | EC:1.1.1.184 |
Cortisol | 5beta-dihydrocortisol | mim-conversion | 46645 (Rhea) | EC:1.3.1.3 |
Cortisol | 6beta-hydroxycortisol | mim-conversion | 55829 (Rhea) | EC:1.14.14.1 |
Cortisol | Cortisone | mim-conversion | 68618 (Rhea) | EC: 1.1.1.146 |
Cortisone | 4,5beta-Dihydrocortisone | mim-conversion | 14039 (Rhea) | EC:1.3.1.3 |
Cortisone | Cortisol | mim-conversion | 68617 (Rhea) |