Enoyl-CoA hydratase

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enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase
Chr. 3 q26.3-q28
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Enoyl-CoA hydratase (ECH) or crotonase

carbons on 2-trans/cis-enoyl-CoA:[2]

ECH is essential to

acetyl CoA and energy in the form of ATP.[2]

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 rate for short chain fatty acids is equivalent to that of diffusion-controlled reactions.[3]

Metabolism

Fatty acid metabolism

ECH

β-oxidation).[4] Fatty acid metabolism is how human bodies turn fats into energy. Fats in foods are generally in the form of triglycerols
. 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

Diagram of leucine, HMB, and isovaleryl-CoA metabolism in humans
α-Ketoglutarate
Glutamate
Glutamate
Pyruvate
α-Ketoisocaproate
(α-KIC)
α-Ketoisocaproate
(α-KIC)
mitochondria
)
Excreted
in urine
(10–40%)


(
HMG-CoA
lyase
Enoyl-CoA hydratase
HMG-CoA 
synthase
Unknown
enzyme
β-Hydroxybutyrate
Acetoacetate
Mevalonate
The image above contains clickable links
Human metabolic pathway for HMB and isovaleryl-CoA relative to L-leucine.[5][6][7] Of the two major pathways, L-leucine is mostly metabolized into isovaleryl-CoA, while only about 5% is metabolized into HMB.[5][6][7]

Mechanism

ECH is used in β-oxidation to add a hydroxyl group and 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.

Concerted reaction.

It is also known from experimental data that no other sources of protons reside in the

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 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.[8]

ECH is mechanistically similar to fumarase.

References

  1. ^ "EC 4.2.1.17". www.sbcs.qmul.ac.uk. Retrieved 2018-09-05.
  2. ^
    PMID 11080293
    .
  3. .
  4. .
  5. ^ .
  6. ^
    ISBN 978-0-12-387784-0. Retrieved 6 June 2016. Energy fuel: Eventually, most Leu is broken down, providing about 6.0kcal/g. About 60% of ingested Leu is oxidized within a few hours ... Ketogenesis: A significant proportion (40% of an ingested dose) is converted into acetyl-CoA and thereby contributes to the synthesis of ketones, steroids, fatty acids, and other compounds
    Figure 8.57: Metabolism of L-leucine
  7. .

External links