View source for Enoyl-CoA hydratase

{{protein
|Name=enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase
|caption=
|image=
|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
}}

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}}| '''Enoyl-CoA Hydratase: active site and substrate''' <!-- replace if not identical with the article name -->
[[Image:enzyme hexamer.png|350px]]
|-
|Crystal structure of Enoyl-CoA Hydratase from a Rat
|-
| Active Site
| Orange
|-
| Substrate
|Red
|-
|}

'''Enoyl-CoA hydratase''' is an [[enzyme]] that hydrates the double bond between the second and third [[carbons]] on acyl-CoA.  This enzyme, also known as crotonase, is essential to [[metabolizing]] [[fatty acids]] to produce both [[acetyl CoA]] and [[energy]].<ref>Bahnson, Brian J., Vernon E. Anderson, and Gregory A. Petsko. "Structural Mechanism of Enoyl-CoA Hydratase: Three Atoms From a Single Water are Added in Either an E1cb Stepwise or Concerted Fashion." Biochemistry 41 (2002): 2621-2629. SciFinder Scholar. 2 December 2007.</ref>  Note the crystal structure at right of enoyl-coa hydratase from a rat.  The crystal structure shows a hexamer formation (not universal, but human enzyme is also hexameric), which leads to the efficiency of this [[protein]].  This enzyme has been discovered to be highly efficient, and allows our bodies to metabolize fatty acids into energy very quickly.  In fact this enzyme is so efficient that the [[reaction rate|rate]] is equivalent to that of diffusion-controlled [[Chemical reaction|reactions]].<ref>TEngel, Christian K., Tiila R. Kiema, J. Kalervo Hiltunen, and Rik K. Wierenga. "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 of Molecular Biology 275 (1998): 847-859. SciFinder Scholar. 2 December 2007.</ref>

==Biological Significance: Metabolism==
Enoyl-CoA hydratase [[catalyzes]] the second step in the breakdown of fatty acids or the second step of [[β-oxidation]] in fatty acid metabolism shown below.  Fatty acid metabolism is how our bodies turn [[fat]]s or [[lipids]] into energy.  When fats come into our bodies, they are generally in the form of triacyl-glycerols.  These must be broken down in order for the fats to pass into our bodies.  When that happens, three fatty acids are released.

In [[fatty acid metabolism]], fatty acids are changed into fatty acyl-CoA.  To do this, the [[carboxylate]] which occupies one end of the fatty acid is changed into a [[thioester]] by substituting coenzyme A for the [[hydroxyl group]].  Next the fatty acyl-CoA is [[oxidized]] and broken down into an acetyl-CoA molecule and another acyl-CoA.  The acetyl CoA is then sent to the [[citric acid cycle]] while the remaining acyl-CoA is broken down further into acetyl-CoAs.  The complete breakdown of a fatty acid not only generates acetyl-CoA molecules, but it also generates energy in the form of [[NADH]].  This NADH goes on to be converted into ATP which can be used in other reactions.<ref>Nelson, David L., and Michael M. Cox. Lehninger Principles of Biochemistry. 4th ed. New York: W. H. Freeman and Company, 2005. 637-643.</ref>

<!-- Image with unknown copyright status removed: [[Image:fatty_acid_catabolism.gif]] -->
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}}| '''Active Site Orientation''' <!-- replace if not identical with the article name -->
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|[[Image:active site orientation.png|350px]]
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===Leucine metabolism===
{{Leucine metabolism in humans|align=center}}

==Mechanism==
Enoyl-CoA hydratase (ECH) is used in β-oxidation to add a hydroxyl group and a [[proton]] to the unsaturated [[β-carbon]] on a fatty-acyl CoA.  The enzyme 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. 

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 the enzyme 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, as seen in figure 1. This configuration requires that the active site for this enzyme 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 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>Bahnson, Brian J., Vernon E. Anderson, and Gregory A. Petsko. "Structural Mechanism of Enoyl-CoA Hydratase: Three Atoms From a Single Water are Added in Either an E1cb Stepwise or Concerted Fashion." Biochemistry 41 (2002): 2621-2629. SciFinder Scholar. 2 December 2007.</ref>  Both mechanisms are shown below.

{| class="toccolours" border="1" style="float: center; clear: center; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}}| '''Reaction Mechanisms''' <!-- replace if not identical with the article name -->
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|Figure 2: Both Mechanisms
|Figure 3: Concerted Mechanism
|-
|<!-- Image with unknown copyright status removed: [[Image:mechanism_for_wiki.gif]] -->
|[[Image:chimera mechanism.gif|350px]]
|-
|}

The enzyme is mechanistically similar to [[fumarase]].

It is classified as {{EC number|4.2.1.17}}.

==References==
{{Reflist}}

==External links==
* {{MeshName|Enoyl-CoA+Hydratase}}

{{Lipid metabolism enzymes}}
{{Carbon-oxygen lyases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:EC 4.2.1]]