11-Beta hydroxysteroid dehydrogenase
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11-Beta hydroxysteroid dehydrogenase
| 11-beta-hydroxysteroid dehydrogenase (NADP+) | |||||||
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| Identifiers | |||||||
| EC number | 1.1.1.146 | ||||||
| CAS number | 9041-46-7 | ||||||
| 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 11beta-dehydrogenase, beta-hydroxysteroid dehydrogenase, 11beta-hydroxy steroid dehydrogenase, corticosteroid 11-reductase, and dehydrogenase, 11beta-hydroxy steroid. This enzyme participates in c21-steroid hormone metabolism and androgen and estrogen metabolism.
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Contents
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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. HSD-11β co-localizes with intracellular adrenal steroid receptors. Licorice or Carbenoxolone , which contains glycyrrhetinic acid, 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 colon, salivary glands, 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
References
- ^ Seckl JR, Walker BR (April 2001). "Minireview: 11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocorticoid action". Endocrinology 142 (4): 1371–6. DOI:10.1210/en.142.4.1371. PMID 11250914. http://endo.endojournals.org/cgi/pmidlookup?view=long&pmid=11250914.
- ^ Seckl JR (January 1997). "11beta-Hydroxysteroid dehydrogenase in the brain: a novel regulator of glucocorticoid action?". Front Neuroendocrinol 18 (1): 49–99. DOI:10.1006/frne.1996.0143. PMID 9000459. http://linkinghub.elsevier.com/retrieve/pii/S0091-3022(96)90143-0.
- ^ a b Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP (2009). "Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: a hypothesis". The Journal of Clinical Endocrinology and Metabolism 94 (8): 2692–2701. DOI:10.1210/jc.2009-0370. PMID 19470627. http://jcem.endojournals.org/cgi/content/full/94/8/2692.
- Agarwal AK, Monder C, Eckstein B, White PC (1989). "Cloning and expression of rat cDNA encoding corticosteroid 11 beta-dehydrogenase". J. Biol. Chem. 264 (32): 18939–43. PMID 2808402.
- Bush IE, Hunter SA, Meigs RA (1968). "Metabolism of 11-oxygenated steroids. Metabolism in vitro by preparations of liver". Biochem. J. 107 (2): 239–58. PMC 1198650. PMID 4384445. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1198650.
- Lakshmi V, Monder C (1988). "Purification and characterization of the corticosteroid 11 beta-dehydrogenase component of the rat liver 11 beta-hydroxysteroid dehydrogenase complex". Endocrinology. 123 (5): 2390–8. DOI:10.1210/endo-123-5-2390. PMID 3139396.
- Phillips DM, Lakshmi V, Monder C (1989). "Corticosteroid 11 beta-dehydrogenase in rat testis". Endocrinology. 125 (1): 209–16. DOI:10.1210/endo-125-1-209. PMID 2661206.
External links
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