エノイルCoAヒドラターゼ
WordNet
- the 3rd letter of the Roman alphabet (同)c
- (music) the keynote of the scale of C major
- a general-purpose programing language closely associated with the UNIX operating system
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- carbonの化学記号
- cobaltの化学記号
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/24 17:23:37」(JST)
[Wiki en表示]
| enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase |
| Identifiers |
| Symbol |
EHHADH |
| Alt. symbols |
ECHD |
| Entrez |
1962 |
| HUGO |
3247 |
| OMIM |
607037 |
| RefSeq |
NM_001966 |
| UniProt |
Q08426 |
| Other data |
| EC number |
4.2.1.17 |
| Locus |
Chr. 3 q26.3-q28 |
| Enoyl-CoA Hydratase: active site and substrate
|
| 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.[1] 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 rate is equivalent to that of diffusion-controlled reactions.[2]
Contents
- 1 Biological Significance: Metabolism
- 2 Mechanism
- 3 References
- 4 External links
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 fats 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.[3]
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 residues as catalytic acid and 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 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.[4] Both mechanisms are shown below.
| Reaction Mechanisms |
| Figure 2: Both Mechanisms |
Figure 3: Concerted Mechanism |
|
|
The enzyme is mechanistically similar to fumarase.
It is classified as EC 4.2.1.17.
References
- ^ 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.
- ^ 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.
- ^ Nelson, David L., and Michael M. Cox. Lehninger Principles of Biochemistry. 4th ed. New York: W. H. Freeman and Company, 2005. 637-643.
- ^ 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.
External links
- Enoyl-CoA Hydratase at the US National Library of Medicine Medical Subject Headings (MeSH)
|
Carbon-oxygen lyases (EC 4.2) (primarily dehydratases)
|
|
| 4.2.1: Hydro-Lyases |
- Carbonic anhydrase
- Fumarase
- Aconitase
- Enolase
- Enoyl-CoA hydratase/3-Hydroxyacyl ACP dehydrase
- Methylglutaconyl-CoA hydratase
- Tryptophan synthase
- Cystathionine beta synthase
- Porphobilinogen synthase
- 3-Isopropylmalate dehydratase
- Urocanase
- Uroporphyrinogen III synthase
- Nitrile hydratase
|
|
| 4.2.2: Acting on polysaccharides |
|
|
| 4.2.3: Acting on phosphates |
|
|
| 4.2.99: Other |
- Carboxymethyloxysuccinate lyase
|
|
- Biochemistry overview
- Enzymes overview
- By EC number: 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
|
|
|
|
|
Metabolism: lipid metabolism / fatty acid metabolism, triglyceride and fatty acid enzymes
|
|
| Synthesis |
| Malonyl-CoA synthesis |
- ATP citrate lyase
- Acetyl-CoA carboxylase
|
|
Fatty acid synthesis/
Fatty acid synthase |
- Beta-ketoacyl-ACP synthase
- Β-Ketoacyl ACP reductase
- 3-Hydroxyacyl ACP dehydrase
- Enoyl ACP reductase
|
|
| Fatty acid desaturases |
- Stearoyl-CoA desaturase-1
|
|
| Triacyl glycerol |
- Glycerol-3-phosphate dehydrogenase
- Thiokinase
|
|
|
| Degradation |
| Acyl transport |
- Carnitine palmitoyltransferase I
- Carnitine-acylcarnitine translocase
- Carnitine palmitoyltransferase II
|
|
| Beta oxidation |
| General |
- Acyl CoA dehydrogenase (ACADL
- ACADM
- ACADS
- ACADVL
- ACADSB)
- Enoyl-CoA hydratase
- Acetyl-CoA C-acyltransferase
|
|
| Unsaturated |
- Enoyl CoA isomerase
- 2,4 Dienoyl-CoA reductase
|
|
| Odd chain |
- Propionyl-CoA carboxylase
|
|
| Other |
- Hydroxyacyl-Coenzyme A dehydrogenase
|
|
|
| To acetyl-CoA |
- Malonyl-CoA decarboxylase
|
|
| Aldehydes |
- Long-chain-aldehyde dehydrogenase
|
|
|
|
Index of inborn errors of metabolism
|
|
| Description |
- Metabolism
- Enzymes and pathways: citric acid cycle
- pentose phosphate
- glycoproteins
- glycosaminoglycans
- phospholipid
- cholesterol and steroid
- sphingolipids
- eicosanoids
- amino acid
- urea cycle
- nucleotide
|
|
| Disorders |
- Citric acid cycle and electron transport chain
- Glycoprotein
- Proteoglycan
- Fatty-acid
- Phospholipid
- Cholesterol and steroid
- Eicosanoid
- Amino acid
- Purine-pyrimidine
- Heme metabolism
- Symptoms and signs
|
|
| Treatment |
|
|
Index of nutrition
|
|
| Description |
- Vitamins
- Cofactors
- Metal metabolism
- Fats
- metabolism
- intermediates
- lipoproteins
- Sugars
- Glycolysis
- Glycogenesis and glycogenolysis
- Fructose and galactose
|
|
| Disease |
- Vitamins
- Carbohydrate
- Lipid
- Metals
- Other
- Symptoms and signs
|
|
| Treatment |
- Drugs
- Vitamins
- Mineral supplements
|
|
|
UpToDate Contents
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English Journal
- Biosynthesis of Trehangelin in Polymorphospora rubra K07-0510: Identification of Metabolic Pathway to Angelyl-CoA.
- Inahashi Y1, Shiraishi T2, Palm K3,4, Takahashi Y3, Ōmura S3, Kuzuyama T2, Nakashima T5.
- Chembiochem : a European journal of chemical biology.Chembiochem.2016 Aug 3;17(15):1442-7. doi: 10.1002/cbic.201600208. Epub 2016 Jun 17.
- Trehangelins are trehalose angelates discovered from endophytic actinomycete Polymorphospora rubra K07-0510. We identified the trehangelin biosynthetic gene cluster, including genes that encode a glycoside hydrolase-like protein (thgC), α-amylase (thgD), 3-ketoacyl-ACP synthase III (thgI), 3-keto
- PMID 27311629
- TXNIP regulates myocardial fatty acid oxidation via miR-33a signaling.
- Chen J1, Young ME2, Chatham JC3, Crossman DK4, Dell'Italia LJ2, Shalev A5.
- American journal of physiology. Heart and circulatory physiology.Am J Physiol Heart Circ Physiol.2016 Jul 1;311(1):H64-75. doi: 10.1152/ajpheart.00151.2016. Epub 2016 May 3.
- Myocardial fatty acid β-oxidation is critical for the maintenance of energy homeostasis and contractile function in the heart, but its regulation is still not fully understood. While thioredoxin-interacting protein (TXNIP) has recently been implicated in cardiac metabolism and mitochondrial functio
- PMID 27199118
- Engineering Escherichia coli for the synthesis of short- and medium-chain α,β-unsaturated carboxylic acids.
- Kim S1, Cheong S1, Gonzalez R2.
- Metabolic engineering.Metab Eng.2016 Jul;36:90-8. doi: 10.1016/j.ymben.2016.03.005. Epub 2016 Mar 17.
- Concerns over sustained availability of fossil resources along with environmental impact of their use have stimulated the development of alternative methods for fuel and chemical production from renewable resources. In this work, we present a new approach to produce α,β-unsaturated carboxylic acid
- PMID 26996381
Japanese Journal
- Modification of β-oxidation pathway in Ralstonia eutropha for production of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) from soybean oil(MICROBIAL PHYSIOLOGY AND BIOTECHNOLOGY)
- Preparative synthesis of Poly[(R)-3-hydroxybutyrate] monomer for enzymatic cell-free polymerization
- Preparative synthesis of Poly〔(R)-3-hydroxybutyrate〕 monomer for enzymatic cell-free polymerization
Related Links
- 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.
- 第二の段階では、エノイルCoAヒドラターゼ (enoyl-CoA hydratase) が触媒する反応 により、前段階で形成された二重結合にH2Oが付加され、β-ヒドロキシアシルCoA (β- hydroxyacyl-CoA, 3-hydroxyacyl-CoA) となる。この反応は立体特異的に進み、L体 のみ ...
★リンクテーブル★
[★]
- 英
- peroxisomal bifunctional enzyme
- 関
- ペルオキシソーム、enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase
[★]
- 英
- enoyl-CoA hydratase
- 関
- エノイルCoAヒドラターゼ
[★]
[★]
[★]
ヒドラターゼ、水添加酵素、加水酵素
- 関
- hydrase
[★]
補酵素A coenzyme A CoA
[★]
コバルト cobalt