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| {{enzyme
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| | Name = 11-beta-hydroxysteroid dehydrogenase (NADP<sup>+</sup>)
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| | EC_number = 1.1.1.146
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| | CAS_number = 9041-46-7
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| | IUBMB_EC_number = 1/1/1/146
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| | GO_code = 0033237
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| '''11β-Hydroxysteroid dehydrogenase''' (HSD-11β or 11β-HSD) is the name of a family of [[enzyme]]s that [[catalysis|catalyze]] the conversion of inert 11 keto-products ([[cortisone]]) to active [[cortisol]], or vice versa,<ref name="pmid11250914">{{cite journal |author=Seckl JR, Walker BR |title=Minireview: 11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocorticoid action |journal=Endocrinology |volume=142 |issue=4 |pages=1371–6 |date=April 2001|pmid=11250914 |doi= 10.1210/en.142.4.1371|url=http://endo.endojournals.org/cgi/pmidlookup?view=long&pmid=11250914}}</ref> thus regulating the access of [[glucocorticoid]]s to the steroid receptors:
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| :11β-hydroxysteroid + NADP<sup>+</sup> <math>\rightleftharpoons</math> an 11-oxosteroid + NADPH + H<sup>+</sup>
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| Thus, the two [[substrate (biochemistry)|substrates]] of this enzyme are [[hydroxysteroid|11beta-hydroxysteroid]] and [[nicotinamide adenine dinucleotide phosphate|NADP<sup>+</sup>]], whereas its 3 [[product (chemistry)|products]] are [[oxosteroid|11-oxosteroid]], [[nicotinamide adenine dinucleotide phosphate|NADPH]], and [[hydrogen ion|H<sup>+</sup>]].
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| This enzyme belongs to the family of [[oxidoreductase]]s, specifically those acting on the CH-OH group of donor with NAD<sup>+</sup> or NADP<sup>+</sup> as acceptor. The systematic name of this enzyme class is '''11beta-hydroxysteroid:NADP<sup>+</sup> 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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| ==Structural studies==
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| As of late 2007, 8 [[tertiary structure|structures]] have been solved for this class of enzymes, with [[Protein Data Bank|PDB]] accession codes {{PDB link|1XSE}}, {{PDB link|1XU7}}, {{PDB link|1XU9}}, {{PDB link|1Y5M}}, {{PDB link|1Y5R}}, {{PDB link|2BEL}}, {{PDB link|2ILT}}, and {{PDB link|2IRW}}.
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| ==Function==
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| [[Image:Cortisol2.svg|thumb|left|200px|[[Cortisol]]. Note the OH at the [[Steroid|11 position on ring C]]. (The other differences between the diagrams are not of consequence.)]]
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| [[Image:Cortison.svg|thumb|right|200px|[[Cortisone]]]]
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| 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 [[Apparent mineralocorticoid excess syndrome|mineralocorticoid excess syndrome]].
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| {{-}}
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| ==Isoforms==
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| In humans, there are two HSD11B isoforms:<ref name="pmid9000459">{{cite journal |author=Seckl JR |title=11beta-Hydroxysteroid dehydrogenase in the brain: a novel regulator of glucocorticoid action? |journal=Front Neuroendocrinol |volume=18 |issue=1 |pages=49–99 |date=January 1997|pmid=9000459 |doi=10.1006/frne.1996.0143 |url=http://linkinghub.elsevier.com/retrieve/pii/S0091-3022(96)90143-0}}</ref><ref name="JCEM">{{cite journal | author=Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP | title=Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: a hypothesis | journal=The Journal of Clinical Endocrinology and Metabolism | volume=94 | issue=8 | year=2009 | pages=2692–2701 | url = http://jcem.endojournals.org/cgi/content/full/94/8/2692 | id= | pmid=19470627 | doi=10.1210/jc.2009-0370}}</ref>
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| {| class="wikitable"
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| |-
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| | [[Protein:HSD11B1|HSD11B1]]
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| | [[NADPH]]-dependent
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| | Highly expressed in key metabolic tissues including [[liver]], [[adipose tissue]], and the [[central nervous system]].
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| | In these tissues, HSD11B1 reduces cortisone to the active hormone cortisol that activates [[glucocorticoid receptor]]s.
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| | [[Protein:HSD11B2|HSD11B2]]
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| | [[Nicotinamide adenine dinucleotide|NAD]]<sup>+</sup>-dependent
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| | Expressed in [[aldosterone]]-selective tissues, including kidneys, liver, lungs, colon, salivary glands, [[HSD2 neurons]] and placenta.
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| | In these tissues, HSD11B2 oxidizes cortisol to cortisone and prevents illicit activation of the [[mineralocorticoid receptor]].
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| |}
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| Inhibition of HSD11B1 has been suggested as a possible therapy for treatment of [[obesity]] and [[metabolic syndrome]].<ref name="JCEM" />
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| ==See also==
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| *[[11β-hydroxysteroid dehydrogenase type 1]]
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| *[[Corticosteroid 11-beta-dehydrogenase isozyme 2]]
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| ==References==
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| {{reflist}}
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| * {{cite journal | author = Agarwal AK, Monder C, Eckstein B, White PC | year = 1989 | title = Cloning and expression of rat cDNA encoding corticosteroid 11 beta-dehydrogenase | journal = J. Biol. Chem. | volume = 264 | pages = 18939–43 | pmid = 2808402 | issue = 32 }}
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| * {{cite journal | author = Bush IE, Hunter SA, Meigs RA | year = 1968 | title = Metabolism of 11-oxygenated steroids. Metabolism in vitro by preparations of liver | journal = Biochem. J. | volume = 107 | pages = 239–58 | pmid = 4384445 | issue = 2 | pmc = 1198650 }}
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| * {{cite journal | author = Lakshmi V, Monder C | year = 1988 | title = Purification and characterization of the corticosteroid 11 beta-dehydrogenase component of the rat liver 11 beta-hydroxysteroid dehydrogenase complex | journal = Endocrinology. | volume = 123 | pages = 2390–8 | pmid = 3139396 | doi = 10.1210/endo-123-5-2390 | issue = 5 }}
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| * {{cite journal | author = Phillips DM, Lakshmi V, Monder C | year = 1989 | title = Corticosteroid 11 beta-dehydrogenase in rat testis | journal = Endocrinology. | volume = 125 | pages = 209–16 | pmid = 2661206 | doi = 10.1210/endo-125-1-209 | issue = 1 }}
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| ==External links==
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| * {{MeshName|11-beta-Hydroxysteroid+Dehydrogenases}}
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| {{Alcohol oxidoreductases}}
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| {{Steroid metabolism enymes}}
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| [[Category:EC 1.1.1]]
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| [[Category:NADPH-dependent enzymes]]
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| [[Category:Enzymes of known structure]]
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Hello. Allow me introduce the author. Her name is Emilia Shroyer but it's not the most feminine name out there. My working day job is a meter reader. Doing ceramics is what love performing. His family lives in South Dakota but his spouse wants them to transfer.
Here is my homepage at home std test (please click the next website)