Steroid: Difference between revisions

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Steroids have two principal biological functions: as important components of [[cell membrane]]s that alter [[membrane fluidity]]; and as [[signal transduction|signaling molecules]]. Examples include the [[lipid]] [[cholesterol]], sex hormones [[estradiol]] and [[testosterone]],<ref name = "Lednicer_2011">{{cite book | vauthors = Lednicer D | title = Steroid Chemistry at a Glance | year = 2011 | publisher = Wiley | location = Hoboken | isbn = 978-0-470-66084-3 }}</ref>{{rp|10–19}} [[anabolic steroids]], and the [[anti-inflammatory]] corticosteroid drug [[dexamethasone]].<ref name="pmid16236742">{{cite journal | vauthors = Rhen T, Cidlowski JA | title = Antiinflammatory action of glucocorticoids--new mechanisms for old drugs | journal = The New England Journal of Medicine | volume = 353 | issue = 16 | pages = 1711–1723 | date = October 2005 | pmid = 16236742 | doi = 10.1056/NEJMra050541 | s2cid = 5744727 }}</ref> Hundreds of steroids are found in [[Fungus|fungi]], [[plant]]s, and [[animal]]s. All steroids are manufactured in cells from the [[sterols]] [[lanosterol]] ([[opisthokonts]]) or [[cycloartenol]] (plants). Lanosterol and cycloartenol are derived from the [[Cyclic compound|cyclization]] of the [[triterpene]] [[squalene]].<ref name="urlLanosterol biosynthesis">{{cite web | url = http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/terp/lanost.html | title = Lanosterol biosynthesis | publisher = International Union Of Biochemistry And Molecular Biology | work = Recommendations on Biochemical & Organic Nomenclature, Symbols & Terminology | access-date = 28 November 2006 | archive-url = https://web.archive.org/web/20110308161403/http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/terp/lanost.html | archive-date = 8 March 2011 | url-status = dead }}</ref>

=== Rings and functional groups ===

{{See also|Gonane|Sterane}}

[[Gonane]], also known as steran or cyclopentanoperhydrophenanthrene, the simplest steroid and the nucleus of all steroids and sterols,<ref name="Rogozkin1991">{{cite book|vauthors=Rogozkin VA|chapter=Anabolic Androgenic Steroids: Structure, Nomenclature, and Classification, Biological Properties|title=Metabolism of Anabolic-Androgenic Steroids|chapter-url=https://books.auho.com/books?id=hRsnmJRF1WgC&pg=PA1|date=14 June 1991|publisher=CRC Press|isbn=978-0-8493-6415-0|pages=1–|quote=The steroid structural base is a steran nucleus, a polycyclic C17 steran skeleton consisting of three condensed cyclohexane rings in nonlinear or phenanthrene junction (A, B, and C), and a cyclopentane ring (D).1,2}}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref name="Urich1994">{{cite book| vauthors = Urich K | chapter = Sterols and Steroids |title=Comparative Animal Biochemistry| chapter-url = https://books.google.com/books?id=GLbcWyeaCGQC&pg=PA624 |date=16 September 1994|publisher=Springer Science & Business Media|isbn=978-3-540-57420-0|pages=624–}}</ref> is composed of seventeen [[carbon]] atoms in carbon-carbon bonds forming four [[fused compound|fused ring]]s in a [[Chirality (chemistry)|three-dimensional shape]]. The three [[cyclohexane]] rings (A, B, and C in the first illustration) form the skeleton of a [[hydrogenation|perhydro]] derivative of [[phenanthrene]]. The D ring has a [[cyclopentane]] structure. When the two methyl groups and eight carbon [[side chain]]s (at C-17, as shown for cholesterol) are present, the steroid is said to have a cholestane framework. The two common 5α and 5β stereoisomeric forms of steroids exist because of differences in the side of the largely planar ring system where the hydrogen (H) atom at carbon-5 is attached, which results in a change in steroid A-ring conformation. Isomerisation at the C-21 side chain produces a parallel series of compounds, referred to as isosteroids.{{sfn|Greep|2013}}

 

Examples of steroid structures are:

<gallery>

File:Testosteron.svg|alt=Chemical diagram|[[Testosterone]], the principal male [[Sex steroid|sex hormone]] and an [[anabolic steroid]]

File:Sitosterol structure.svg|alt=Chemical diagram|[[beta-Sitosterol|β-Sitosterol]], a plant or [[phytosterol]], with a fully branched hydrocarbon side chain at C-17 and an hydroxyl group at C-3

</gallery>

In addition to the ring scissions (cleavages), [[ring expansion|expansions]] and [[ring contraction|contractions]] (cleavage and reclosing to a larger or smaller rings)—all variations in the carbon-carbon bond framework—steroids can also vary:

* in the [[bond order]]s within the rings,

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== Species distribution ==

{{Expert needed|pharmacology|section|talk=|reason=to examine this and the following section (and throughout), and to remove redundancies of listed content, and to ensure sourcing for the listed content that remains in any section|date=March 2017}}

 

{{missing information|section|non-eukaryotic type sterol framework – see PMID 27446030, fig 4/5, group 1 [[oxidosqualene cyclase]]|date=November 2021}}

In [[prokaryotes]], biosynthetic pathways exist for the tetracyclic steroid framework (e.g. in [[myxobacteria]])<ref name="pmid12519197">{{cite journal | vauthors = Bode HB, Zeggel B, Silakowski B, Wenzel SC, Reichenbach H, Müller R | title = Steroid biosynthesis in prokaryotes: identification of myxobacterial steroids and cloning of the first bacterial 2,3(S)-oxidosqualene cyclase from the myxobacterium Stigmatella aurantiaca | journal = Molecular Microbiology | volume = 47 | issue = 2 | pages = 471–81 | date = Jan 2003 | pmid = 12519197 | doi = 10.1046/j.1365-2958.2003.03309.x | s2cid = 37959511 | doi-access = }}</ref> – where its origin from [[eukaryote]]s is conjectured<ref name="pmid20333205">{{cite journal | vauthors = Desmond E, Gribaldo S | title = Phylogenomics of sterol synthesis: insights into the origin, evolution, and diversity of a key eukaryotic feature | journal = Genome Biology and Evolution | volume = 1 | pages = 364–81 | year = 2009 | pmid = 20333205 | pmc = 2817430 | doi = 10.1093/gbe/evp036 }}</ref> – and the more-common pentacyclic [[triterpene|triterpinoid]] [[hopane|hopanoid]] framework.<ref name="pmid21531832">{{cite journal | vauthors = Siedenburg G, Jendrossek D | title = Squalene-hopene cyclases | journal = Applied and Environmental Microbiology | volume = 77 | issue = 12 | pages = 3905–15 | date = Jun 2011 | pmid = 21531832 | pmc = 3131620 | doi = 10.1128/AEM.00300-11 | bibcode = 2011ApEnM..77.3905S }}</ref>

 

{{expand section|a more full discussion of this most prominent structural type | small = no|date=March 2017}}

Steroids can be classified based on their chemical composition.<ref name="Zorea-2014">{{cite book|title=Steroids (Health and Medical Issues Today)| vauthors = Zorea A |publisher=Greenwood Press|year=2014|isbn=978-1-4408-0299-7|location=Westport, CT|pages=10–12}}</ref> One example of how [[Medical Subject Headings|MeSH]] performs this classification is available at the Wikipedia MeSH catalog. Examples of this classification include:

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[[Norsteroid]]s ([[nor-]], L. ''norma''; "normal" in chemistry, indicating carbon removal)<ref name=iupacRF41>{{cite web | publisher = International Union of Pure and Applied Chemistry (IUPAC) | year = 1999 | title = IUPAC Recommendations: Skeletal Modification in Revised Section F: Natural Products and Related Compounds (IUPAC Recommendations 1999) | url = http://www.chem.qmul.ac.uk/iupac/sectionF/RF41.html#41 | access-date = 20 May 2014 | archive-date = 4 March 2016 | archive-url = https://web.archive.org/web/20160304041709/http://www.chem.qmul.ac.uk/iupac/sectionF/RF41.html#41 | url-status = live }}</ref> and homosteroids (homo-, Greek ''homos''; "same", indicating carbon addition) are structural subclasses of steroids formed from biosynthetic steps. The former involves enzymic [[ring expansion|ring expansion-contraction]] reactions, and the latter is accomplished ([[biomimetic synthesis|biomimetically]]) or (more frequently) through [[ring closure]]s of [[open-chain compound|acyclic]] precursors with more (or fewer) ring atoms than the parent steroid framework.<ref name=Wolfing07>{{cite journal | vauthors = Wolfing J | date = 2007 | title = Recent developments in the isolation and synthesis of D-homosteroids and related compounds | journal = Arkivoc | volume = 2007 | issue = 5 | pages = 210–230 | doi = 10.3998/ark.5550190.0008.517 | url = http://www.arkat-usa.org/get-file/19924/ | doi-access = free | hdl = 2027/spo.5550190.0008.517 | hdl-access = free | access-date = 20 May 2014 | archive-date = 1 February 2013 | archive-url = https://web.archive.org/web/20130201091834/http://www.arkat-usa.org/get-file/19924/ | url-status = live }}</ref>

 

 

== Biological significance ==

== Biosynthesis and metabolism ==

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The hundreds of steroids found in animals, fungi, and [[plant]]s are made from [[lanosterol]] (in animals and fungi; see examples above) or [[cycloartenol]] (in other eukaryotes). Both lanosterol and cycloartenol derive from [[Cyclic compound|cyclization]] of the [[triterpene|triterpenoid]] [[squalene]].<ref name="urlLanosterol biosynthesis"/> Lanosterol and cycloartenol are sometimes called protosterols because they serve as the starting compounds for all other steroids.

 

=== Mevalonate pathway ===

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{{Main|Mevalonate pathway}}

The mevalonate pathway (also called HMG-CoA reductase pathway) begins with [[acetyl-CoA]] and ends with [[dimethylallyl pyrophosphate|dimethylallyl diphosphate]] (DMAPP) and [[isopentenyl pyrophosphate|isopentenyl diphosphate]] (IPP).

=== <span class="anchor" id="Regulation">Steroidogenesis</span> ===

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{{See also|Steroidogenic enzyme}}