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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== | |
| 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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| |-
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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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