Corticosteroid 11-beta-dehydrogenase isozyme 2

Short description: Enzyme found in humans

Generic protein structure example

Corticosteroid 11-β-dehydrogenase isozyme 2 also known as 11-β-hydroxysteroid dehydrogenase 2 is an enzyme that in humans is encoded by the HSD11B2 gene.[1][2][3]

## Contents

* 1 Function
* 2 Clinical significance
* 3 References
* 4 Further reading

## Function

Corticosteroid 11-β-dehydrogenase isozyme 2 is an NAD+-dependent enzyme expressed in aldosterone-selective epithelial tissues such as the kidney, colon, salivary and sweat glands. HSD211B2 expression is also found in the brainstem in a small, aldosterone-sensitive subset of neurons located in the nucleus of the solitary tract referred to as HSD2 neurons.[4]

In these tissues, HSD11B2 oxidizes the glucocorticoid cortisol to the inactive metabolite cortisone, thus preventing illicit activation of the mineralocorticoid receptor. This protective mechanism is necessary because cortisol circulates at 100- to 1000-fold higher concentrations than aldosterone, and binds with equal affinity to the mineralocorticoid receptor, thereby out-competing aldosterone in cells that do not produce HSD11B2.

This glucocorticoid-inactivating enzyme is also expressed in tissues that do not express the mineralocorticoid receptor, such as the placenta and testis, as well as parts of the developing brain, including the rhombencephalic progenitor cells that proliferate into cerebellar granule cells. In these tissues, HSD11B2 protects cells from the growth-inhibiting and/or pro-apoptotic effects of cortisol, particularly during embryonic development.

## Clinical significance

Inhibition of this enzyme, for example by the compound glycyrrhetinic acid enzymatically converted from glycyrrhizic acid, found in natural liquorice, results in a condition known as pseudohyperaldosteronism. A genetically inherited deficiency of HSD11B2 is the underlying cause of the syndrome of apparent mineralocorticoid excess.

## References

1. ↑ "Cloning and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme". Mol. Cell. Endocrinol. 105 (2): R11–7. November 1994. doi:10.1016/0303-7207(94)90176-7. PMID 7859916.
2. ↑ "Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2". Biochem. J. 313 (Pt 3): 1007–17. February 1996. doi:10.1042/bj3131007. PMID 8611140.
3. ↑ "Entrez Gene: HSD11B2 hydroxysteroid (11-beta) dehydrogenase 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3291.
4. ↑ Geerling, Joel C.; Arthur D. Loewy (September 2009). "Aldosterone in the brain". American Journal of Physiology. Renal Physiology 297 (3): F559–76. doi:10.1152/ajprenal.90399.2008. PMID 19261742.

## Further reading

* "11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess". Endocr. Rev. 18 (1): 135–56. 1997. doi:10.1210/edrv.18.1.0288. PMID 9034789.
* Wilson RC; Dave-Sharma S; Wei JQ et al. (1998). "A genetic defect resulting in mild low-renin hypertension". Proc. Natl. Acad. Sci. U.S.A. 95 (17): 10200–5. doi:10.1073/pnas.95.17.10200. PMID 9707624. Bibcode: 1998PNAS...9510200W.
* "Hypertension and the cortisol-cortisone shuttle". J. Clin. Endocrinol. Metab. 88 (6): 2384–92. 2003. doi:10.1210/jc.2003-030138. PMID 12788832.
* Tomlinson JW; Walker EA; Bujalska IJ et al. (2005). "11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response". Endocr. Rev. 25 (5): 831–66. doi:10.1210/er.2003-0031. PMID 15466942.
* Persu A (2005). "11beta-Hydroxysteroid deshydrogenase: a multi-faceted enzyme". J. Hypertens. 23 (1): 29–31. doi:10.1097/00004872-200501000-00007. PMID 15643119.
* "Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated". Science 242 (4878): 583–5. 1988. doi:10.1126/science.2845584. PMID 2845584. Bibcode: 1988Sci...242..583F.
* Stewart PM; Wallace AM; Valentino R et al. (1987). "Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age". Lancet 2 (8563): 821–4. doi:10.1016/S0140-6736(87)91014-2. PMID 2889032.
* Wilson RC; Harbison MD; Krozowski ZS et al. (1995). "Several homozygous mutations in the gene for 11 beta-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess". J. Clin. Endocrinol. Metab. 80 (11): 3145–50. doi:10.1210/jcem.80.11.7593417. PMID 7593417.
* Wilson RC; Krozowski ZS; Li K et al. (1995). "A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess". J. Clin. Endocrinol. Metab. 80 (7): 2263–6. doi:10.1210/jcem.80.7.7608290. PMID 7608290.
* "Localization of the gene for human 11 beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) to chromosome band 16q22". Cytogenet. Cell Genet. 71 (2): 124–5. 1995. doi:10.1159/000134089. PMID 7656579.
* Mune T; Rogerson FM; Nikkilä H et al. (1995). "Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase". Nat. Genet. 10 (4): 394–9. doi:10.1038/ng0895-394. PMID 7670488.
* "Gene structure and chromosomal localization of the human HSD11K gene encoding the kidney (type 2) isozyme of 11 beta-hydroxysteroid dehydrogenase". Genomics 29 (1): 195–9. 1996. doi:10.1006/geno.1995.1231. PMID 8530071.
* Krozowski Z; Albiston AL; Obeyesekere VR et al. (1996). "The human 11 beta-hydroxysteroid dehydrogenase type II enzyme: comparisons with other species and localization to the distal nephron". J. Steroid Biochem. Mol. Biol. 55 (5–6): 457–64. doi:10.1016/0960-0760(95)00194-8. PMID 8547170.
* Brown RW; Chapman KE; Murad P et al. (1996). "Purification of 11 beta-hydroxysteroid dehydrogenase type 2 from human placenta utilizing a novel affinity labelling technique". Biochem. J. 313 (Pt 3): 997–1005. doi:10.1042/bj3130997. PMID 8611186.
* Kitanaka S; Katsumata N; Tanae A et al. (1998). "A new compound heterozygous mutation in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess". J. Clin. Endocrinol. Metab. 82 (12): 4054–8. doi:10.1210/jcem.82.12.4455. PMID 9398712.
* Dave-Sharma S; Wilson RC; Harbison MD et al. (1998). "Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess". J. Clin. Endocrinol. Metab. 83 (7): 2244–54. doi:10.1210/jcem.83.7.4986. PMID 9661590.
* Li A; Tedde R; Krozowski ZS et al. (1998). "Molecular basis for hypertension in the "type II variant" of apparent mineralocorticoid excess". Am. J. Hum. Genet. 63 (2): 370–9. doi:10.1086/301955. PMID 9683587.

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Metabolism: lipid metabolism – ketones/cholesterol synthesis enzymes/steroid metabolism

Mevalonate pathway|

| To HMG-CoA|

* Acetyl-Coenzyme A acetyltransferase
* HMG-CoA synthase (regulated step)

|

Ketogenesis|

* HMG-CoA lyase
* 3-hydroxybutyrate dehydrogenase
* Thiophorase

To Mevalonic acid|

* HMG-CoA reductase

To DMAPP|

* Mevalonate kinase
* Phosphomevalonate kinase
* Pyrophosphomevalonate decarboxylase
* Isopentenyl-diphosphate delta isomerase

Geranyl-|

* Dimethylallyltranstransferase
* Geranyl pyrophosphate

To cholesterol|

| To lanosterol|

* Farnesyl-diphosphate farnesyltransferase
* Squalene monooxygenase
* Lanosterol synthase

|

7-Dehydrocholesterol path|

* Lanosterol 14α-demethylase
* Sterol-C5-desaturase-like
* 7-Dehydrocholesterol reductase

Desmosterol path|

* 24-Dehydrocholesterol reductase

To Bile acids|

* Cholesterol 7α-hydroxylase
* Sterol 27-hydroxylase

Steroidogenesis|

| To pregnenolone|

* Cholesterol side-chain cleavage

|

To corticosteroids|

* aldosterone: 18-Hydroxylase

* cortisol/cortisone: 17α-Hydroxylase
* 11β-HSD
* 1
* 2

* both: 3β-HSD
* 1
* 2
* 21-Hydroxylase
* 11β-Hydroxylase

To sex hormones|

| To androgens|

* 17α-Hydroxylase
* 17,20-Lyase
* 3β-HSD
* 17β-HSD
* 5α-Reductase
* 1
* 2

|

To estrogens|

* Aromatase
* 17β-HSD

Other/ungrouped|

* Steroid metabolism: sulfatase
* Steroid sulfatase
* sulfotransferase
* SULT1A1
* SULT2A1

* Steroidogenic acute regulatory protein
* Cholesterol total synthesis
* Reverse cholesterol transport

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* e

Oxidoreductases: alcohol oxidoreductases (EC 1.1)

1.1.1: NAD/NADP acceptor|

* 3-hydroxyacyl-CoA dehydrogenase
* 3-hydroxybutyryl-CoA dehydrogenase
* Alcohol dehydrogenase
* Aldo-keto reductase
* 1A1
* 1B1
* 1B10
* 1C1
* 1C3
* 1C4
* 7A2
* Aldose reductase
* Beta-Ketoacyl ACP reductase
* Carbohydrate dehydrogenases
* Carnitine dehydrogenase
* D-malate dehydrogenase (decarboxylating)
* DXP reductoisomerase
* Glucose-6-phosphate dehydrogenase
* Glycerol-3-phosphate dehydrogenase
* HMG-CoA reductase
* IMP dehydrogenase
* Isocitrate dehydrogenase
* Lactate dehydrogenase
* L-threonine dehydrogenase
* L-xylulose reductase
* Malate dehydrogenase
* Malate dehydrogenase (decarboxylating)
* Malate dehydrogenase (NADP+)
* Malate dehydrogenase (oxaloacetate-decarboxylating)
* Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+)
* Phosphogluconate dehydrogenase
* Sorbitol dehydrogenase

* Hydroxysteroid dehydrogenase: 3β
* 3β-HSD
* NSDHL
* 11β
* 11β-HSD1
* 11β-HSD2
* 17β

1.1.2: cytochrome acceptor|

* D-lactate dehydrogenase (cytochrome)
* D-lactate dehydrogenase (cytochrome c-553)
* Mannitol dehydrogenase (cytochrome)

1.1.3: oxygen acceptor|

* Glucose oxidase
* L-gulonolactone oxidase
* Xanthine oxidase

1.1.4: disulfide as acceptor|

* Vitamin K epoxide reductase
* Vitamin-K-epoxide reductase (warfarin-insensitive)

1.1.5: quinone/similar acceptor|

* Malate dehydrogenase (quinone)
* Quinoprotein glucose dehydrogenase

1.1.99: other acceptors|

* Choline dehydrogenase
* L2HGDH

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Enzymes

Activity|

* Active site
* Binding site
* Catalytic triad
* Oxyanion hole
* Enzyme promiscuity
* Catalytically perfect enzyme
* Coenzyme
* Cofactor
* Enzyme catalysis

Regulation|

* Allosteric regulation
* Cooperativity
* Enzyme inhibitor
* Enzyme activator

Classification|

* EC number
* Enzyme superfamily
* Enzyme family
* List of enzymes

Kinetics|

* Enzyme kinetics
* Eadie–Hofstee diagram
* Hanes–Woolf plot
* Lineweaver–Burk plot
* Michaelis–Menten kinetics

Types|

* EC1 Oxidoreductases (list)
* EC2 Transferases (list)
* EC3 Hydrolases (list)
* EC4 Lyases (list)
* EC5 Isomerases (list)
* EC6 Ligases (list)
* EC7 Translocases (list)

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Original source: https://en.wikipedia.org/wiki/Corticosteroid 11-beta-dehydrogenase isozyme 2. Read more

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*[HSD]: Hydroxysteroid dehydrogenase