11-Beta hydroxysteroid dehydrogenase
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| 11-beta-hydroxysteroid dehydrogenase (NADP+) | |||||||||
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| Identifiers | |||||||||
| EC number | 1.1.1.146 | ||||||||
| CAS number | Template:CAS | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / EGO | ||||||||
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11β-Hydroxysteroid dehydrogenase (HSD-11β or 11β-HSD) is the name of a family of enzymes that catalyze the conversion of inert 11 keto-products (cortisone) to active cortisol, or vice versa,[1] thus regulating the access of glucocorticoids to the steroid receptors:
- 11β-hydroxysteroid + NADP+
an 11-oxosteroid + NADPH + H+
Thus, the two substrates of this enzyme are 11beta-hydroxysteroid and NADP+, whereas its 3 products are 11-oxosteroid, NADPH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 11beta-hydroxysteroid:NADP+ 11-oxidoreductase. Other names in common use include corticosteroid 11β-dehydrogenase, β-hydroxysteroid dehydrogenase, 11β-hydroxy steroid dehydrogenase, corticosteroid 11-reductase, and dehydrogenase, 11β-hydroxy steroid. This enzyme participates in c21-steroid hormone metabolism and androgen and estrogen metabolism.
Structural studies
As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes 1XSE, 1XU7, 1XU9, 1Y5M, 1Y5R, 2BEL, 2ILT, and 2IRW.
Function
Cortisol, a glucocorticoid, binds the glucocorticoid receptor. However, because of its molecular similarity to aldosterone it is also capable of binding the mineralcorticoid receptor. Both aldosterone and cortisol have a similar affinity for the mineralocorticoid receptor; however, there is vastly more cortisol in circulation than aldosterone. To prevent over-stimulation of the mineralocorticoid receptor by cortisol, HSD-11β converts the biologically active cortisol to the inactive cortisone, which can no longer bind to the mineralocorticoid receptor. 11β-HSD co-localizes with intracellular adrenal steroid receptors. Licorice, which contains glycyrrhetinic acid, or Carbenoxolone can inhibit 11β-HSD and lead to a mineralocorticoid excess syndrome.
Isoforms
In humans, there are two HSD11B isoforms:[2][3]
| HSD11B1 | NADPH-dependent | Highly expressed in key metabolic tissues including liver, adipose tissue, and the central nervous system. | In these tissues, HSD11B1 reduces cortisone to the active hormone cortisol that activates glucocorticoid receptors. |
| HSD11B2 | NAD+-dependent | Expressed in aldosterone-selective tissues, including kidneys, liver, lungs, colon, salivary glands, HSD2 neurons and placenta. | In these tissues, HSD11B2 oxidizes cortisol to cortisone and prevents illicit activation of the mineralocorticoid receptor. |
Inhibition of HSD11B1 has been suggested as a possible therapy for treatment of obesity and metabolic syndrome.[3]
See also
- 11β-hydroxysteroid dehydrogenase type 1
- 11β-hydroxysteroid dehydrogenase type 2
- Cortisone reductase deficiency
References
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External links
- 11-beta-Hydroxysteroid Dehydrogenases at the US National Library of Medicine Medical Subject Headings (MeSH)
