View source for Enoyl-CoA hydratase

{{Short description|Class of enzymes}}
{{protein
|Name=enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase
|caption=Enoyl-CoA hydratase hexamer from a rat with active site in orange and substrate in red.
|image=enzyme hexamer.png
|width=
|HGNCid=3247
|Symbol=EHHADH
|AltSymbols=ECHD
|EntrezGene=1962
|OMIM=607037
|RefSeq=NM_001966
|UniProt=Q08426
|PDB=
|ECnumber=4.2.1.17
|Chromosome=3
|Arm=q
|Band=26.3
|LocusSupplementaryData=-q28
}}
'''Enoyl-CoA hydratase''' (ECH) or '''crotonase'''<ref>{{Cite web|url=http://www.sbcs.qmul.ac.uk/iubmb/enzyme/EC4/2/1/17.html|title=EC 4.2.1.17|website=www.sbcs.qmul.ac.uk|access-date=2018-09-05}}</ref> is an [[enzyme]] {{EnzExplorer|4.2.1.17}}  that hydrates the double bond between the second and third [[carbons]] on 2-trans/cis-enoyl-CoA:<ref name=":0">{{Cite journal|last=Allenbach|first=L|last2=Poirier|first2=Y|date=2000|title=Analysis of the Alternative Pathways for the β-Oxidation of Unsaturated Fatty Acids Using Transgenic Plants Synthesizing Polyhydroxyalkanoates in Peroxisomes|journal=Plant Physiology|volume=124|issue=3|pages=1159–1168|issn=0032-0889|pmc=59215|pmid=11080293|doi=10.1104/pp.124.3.1159}}</ref>

[[File:Beta-Oxidation2.svg|460x460px]]

[[File:Enoyl-CoA hydratase reaction cis.svg]]

ECH is essential to [[metabolizing]] [[fatty acids]] in [[beta oxidation]] to produce both [[acetyl CoA]] and [[energy]] in the form of [[Adenosine triphosphate|ATP]].<ref name=":0" />

ECH of rats is a [[hexameric protein]] (this trait is not universal, but human enzyme is also hexameric), which leads to the efficiency of this enzyme as it has 6 active sites. This enzyme has been discovered to be highly efficient, and allows people to metabolize fatty acids into energy very quickly. In fact this enzyme is so efficient that the [[reaction rate|rate]] for short chain fatty acids is equivalent to that of diffusion-controlled [[Chemical reaction|reactions]].<ref name="Engel_1998">{{cite journal|vauthors=Engel CK, Kiema TR, Hiltunen JK, Wierenga RK|title=The crystal structure of enoyl-CoA hydratase complexed with octanoyl-CoA reveals the structural adaptations required for binding of a long chain fatty acid-CoA molecule|journal=Journal of Molecular Biology|volume=275|issue=5|pages=847–59|date=February 1998|pmid=9480773|doi=10.1006/jmbi.1997.1491 }}</ref>

==Metabolism==
=== Fatty acid metabolism ===
ECH [[catalyzes]] the second step (hydratation) in the breakdown of fatty acids ([[β-oxidation]]).<ref>{{cite book|title=Lehninger principles of biochemistry|last1=Cox|first1=David L.|last2=Nelson|first2=Michael M.|date=2005|publisher=W.H. Freeman|isbn=978-0-7167-4339-2|edition=4th|location=New York|page=[https://archive.org/details/lehningerprincip00lehn_0/page/647 647-43]|name-list-style=vanc|url-access=registration|url=https://archive.org/details/lehningerprincip00lehn_0/page/647}}</ref> Fatty acid metabolism is how human bodies turn [[fat]]s into energy. Fats in foods are generally in the form of [[triglycerol]]s. These must be broken down in order for the fats to pass into human bodies. When that happens, three fatty acids are released.

===Leucine metabolism===
{{Leucine metabolism in humans|align=center}}

==Mechanism==
ECH is used in β-oxidation to add a hydroxyl group and a [[proton]] to the unsaturated [[β-carbon]] on a fatty-acyl CoA. ECH functions by providing two [[glutamate]] [[residue (chemistry)|residue]]s as catalytic [[acid]] and [[Base (chemistry)|base]]. The two [[amino acids]] hold a [[water]] molecule in place, allowing it to attack in a [[syn addition]] to an α-β unsaturated acyl-CoA at the β-carbon. The α-carbon then grabs another proton, which completes the formation of the beta-hydroxy acyl-CoA.
[[File:Chimera mechanism.gif|thumb|Concerted reaction.]]
It is also known from experimental data that no other sources of protons reside in the [[active site]]. This means that the proton which the α-carbon grabs is from the water that just attacked the β-carbon. What this implies is that the hydroxyl group and the proton from water are both added from the same side of the [[double bond]], a syn addition. This allows ECH to make an S [[stereoisomer]] from 2-trans-enoyl-CoA and an R stereoisomer from the 2-cis-enoyl-CoA. This is made possible by the two [[glutamate]] residues which hold the water in position directly adjacent to the α-β unsaturated double bond. This configuration requires that the active site for ECH is extremely rigid, to hold the water in a very specific configuration with regard to the acyl-CoA. The data for a [[reaction mechanism|mechanism]] for this reaction is not conclusive as to whether this reaction is concerted (shown in the picture) or occurs in consecutive steps. If occurring in consecutive steps, the intermediate is identical to that which would be generated from an [[E1cB-elimination reaction]].<ref name="Bahnson_2002">{{cite journal|vauthors=Bahnson BJ, Anderson VE, Petsko GA|date=February 2002|title=Structural mechanism of enoyl-CoA hydratase: three atoms from a single water are added in either an E1cb stepwise or concerted fashion|journal=Biochemistry|volume=41|issue=8|pages=2621–9|doi=10.1021/bi015844p|pmid=11851409}}</ref>

ECH is mechanistically similar to [[fumarase]].
{{clear}}

==References==
{{Reflist|32em}}

==External links==
*{{MeshName|Enoyl-CoA+Hydratase}}
{{Lipid metabolism enzymes}}
{{Carbon-oxygen lyases}}
{{Enzymes}}
{{Portal bar|Biology|border=no}}

[[Category:EC 4.2.1]]
[[Category:Beta oxidation]]