Glucocorticoid biosynthesis (WP5280)

Homo sapiens

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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. Metabolic reactions currently without a Rhea ID have been added in bold to the pathway model.

Authors

Conroy lipids , Denise Slenter , and Lina Schiffer

Activity

last edited

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

glucocorticoid biosynthetic pathway classic metabolic pathway cortisol biosynthetic pathway lipid metabolic pathway

Participants
Query Drugst.One

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
AKR1C4 GeneProduct uniprot:P17516
AKR1C2 GeneProduct uniprot:P52895
AKR1C3 GeneProduct uniprot:P42330
AKR1C1 GeneProduct uniprot:Q04828
AKR1D1 GeneProduct uniprot:P51857
AKR1D1 GeneProduct uniprot:P51857
AKR1C4 GeneProduct uniprot:P17516
AKR1C2 GeneProduct uniprot:P52895
AKR1C3 GeneProduct uniprot:P42330
AKR1C1 GeneProduct uniprot:Q04828
AKR1D1 GeneProduct uniprot:P51857
AKR1C4 GeneProduct uniprot:P17516
AKR1C2 GeneProduct uniprot:P52895
AKR1C3 GeneProduct uniprot:P42330
AKR1C1 GeneProduct uniprot:Q04828
CYP11B1 GeneProduct uniprot:P15538
HSD11B2 GeneProduct uniprot:P80365
HSD11B1 GeneProduct uniprot:P28845
CYP11B2 GeneProduct uniprot:P19099
AKR1D1 GeneProduct uniprot:P51857
AKR1D1 GeneProduct uniprot:P51857
AKR1D1 GeneProduct uniprot:P51857

References

  1. 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
  2. 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