Information on EC 1.3.8.7 - medium-chain acyl-CoA dehydrogenase and Organism(s) Homo sapiens

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
1.3.8.7
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RECOMMENDED NAME
GeneOntology No.
medium-chain acyl-CoA dehydrogenase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
a medium-chain acyl-CoA + electron-transfer flavoprotein = a medium-chain trans-2,3-dehydroacyl-CoA + reduced electron-transfer flavoprotein
show the reaction diagram
the catalytic base responsible for the alpha-proton abstraction is E376 in medium-chain acyl-CoA dehydrogenase, while that in long-chain acyl-CoA dehydrogenase is E255
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dehydrogenation
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-
-
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oxidation
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-
-
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redox reaction
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-
-
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reduction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
fatty acid salvage
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lipid metabolism
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Fatty acid degradation
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Valine, leucine and isoleucine degradation
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beta-Alanine metabolism
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Propanoate metabolism
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Metabolic pathways
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Biosynthesis of secondary metabolites
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Biosynthesis of antibiotics
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SYSTEMATIC NAME
IUBMB Comments
medium-chain acyl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase
Contains FAD as prosthetic group. One of several enzymes that catalyse the first step in fatty acids beta-oxidation. The enzyme from pig liver can accept substrates with acyl chain lengths of 4 to 16 carbon atoms, but is most active with C8 to C12 compounds [2]. The enzyme from rat does not accept C16 at all and is most active with C6-C8 compounds [4]. cf. EC 1.3.8.1, short-chain acyl-CoA dehydrogenase, EC 1.3.8.8, long-chain acyl-CoA dehydrogenase, and EC 1.3.8.9, very-long-chain acyl-CoA dehydrogenase.
CAS REGISTRY NUMBER
COMMENTARY hide
9027-65-0
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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medium-chain acyl-CoA dehydrogenase deficiency (OMIM 201450) is the most common inherited disorder of fatty acid metabolism presenting with hypoglycaemia, hepatopathy and Reye-like symptoms during catabolism, genotyping and phenotypes, overview. Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(4Z,7Z,10Z,13Z,16Z,19Z)-4,7,10,13,16,19-docosahexaenoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
-
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(5Z,8Z,11Z,14Z,17Z) -5,8,11,14,17-icosapentaenoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
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-
-
-
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2,6-dimethylheptanoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
-
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4,8,12-trimethyltridecanoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
-
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acyl-CoA + acceptor
2,3-dehydroacyl-CoA + reduced acceptor
show the reaction diagram
acyl-CoA + electron transfer flavoprotein
2,3-dehydroacyl-CoA + reduced electron transfer flavoprotein
show the reaction diagram
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first step in beta-oxidation of fatty acids
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?
arachidonoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
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-
-
-
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arachidoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
-
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butanoyl-CoA + acceptor
crotonyl-CoA + reduced acceptor
show the reaction diagram
decanoyl-CoA + acceptor
2-decenoyl-CoA + reduced acceptor
show the reaction diagram
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acceptors: phenazine methosulfate or electron transferring flavoprotein
-
?
decanoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
-
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docosanoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
-
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dodecanoyl-CoA + acceptor
2-dodecenoyl-CoA + reduced acceptor
show the reaction diagram
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acceptors: phenazine methosulfate or electron transferring flavoprotein
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?
elaidoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
-
-
furylpropionyl-CoA + ferricenium hexafluorophosphate
furylacryloyl-CoA + ferrocenium hexafluorophosphate
show the reaction diagram
-
-
-
?
heptadecanoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
-
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hexadecanoyl-CoA + acceptor
2-hexadecenoyl-CoA + reduced acceptor
show the reaction diagram
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acceptors: phenazine methosulfate or electron transferring flavoprotein, very low activity
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?
hexanoyl-CoA + acceptor
2-hexenoyl-CoA + reduced acceptor
show the reaction diagram
hexanoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
-
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indolepropionyl-CoA + ferricenium hexafluorophosphate
indoleacryloyl-CoA + ferrocenium hexafluorophosphate
show the reaction diagram
-
-
-
?
indolepropionyl-CoA + O2
indoleacryloyl-CoA + H2O2
show the reaction diagram
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very low activity
-
?
lauroyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
-
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linoleoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
-
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myristoleoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
-
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myristoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
-
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n-octanoyl-CoA + acceptor
2-octenoyl-CoA + reduced acceptor
show the reaction diagram
-
-
-
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?
n-octanoyl-CoA + phenazine methosulfate + 2,6-dichloroindophenol
2-octenoyl-CoA + reduced acceptor
show the reaction diagram
nonanoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
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octadecanoyl-CoA + acceptor
2-octadecenoyl-CoA + reduced acceptor
show the reaction diagram
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acceptors: phenazine methosulfate or electron transferring flavoprotein, extremely low activity
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?
octanoyl-CoA + acceptor
2-octenoyl-CoA + reduced acceptor
show the reaction diagram
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-
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?
octanoyl-CoA + ferriocenium hexfluorophosphate
2-octenoyl-CoA + reduced acceptor
show the reaction diagram
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-
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?
octanoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
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-
-
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oleoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
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-
-
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palmitoleoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
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-
-
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palmitoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
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-
-
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pentadecanoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
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-
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pentanoyl-CoA + acceptor
2-pentenoyl-CoA + reduced acceptor
show the reaction diagram
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acceptors: phenazine methosulfate or electron transferring flavoprotein
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?
phenylpropionyl-CoA + acceptor
? + reduced acceptor
show the reaction diagram
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-
-
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?
stearoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
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-
-
-
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tetradecanoyl-CoA + acceptor
2-tetradecenoyl-CoA + reduced acceptor
show the reaction diagram
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acceptors: phenazine methosulfate or electron transferring flavoprotein, low activity
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?
undecanoyl-CoA + oxidized electron transfer flavoprotein
? + reduced electron transfer flavoprotein
show the reaction diagram
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-
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[4-(dimethylamino)phenyl]propionyl-CoA + ferricenium hexafluorophosphate
4-(dimethylamino)cinnamoyl-CoA + ferrocenium hexafluorophosphate
show the reaction diagram
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?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acyl-CoA + electron transfer flavoprotein
2,3-dehydroacyl-CoA + reduced electron transfer flavoprotein
show the reaction diagram
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first step in beta-oxidation of fatty acids
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?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(Methylenecyclopropyl)acetyl-CoA
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0.01 mM, 95% inhibition
(R)-(-)-(methylenecyclopropyl)acetyl-CoA
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2-octynoyl-CoA
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iodoacetamide
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2 mM, 73% inhibition
N-ethylmaleimide
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2 mM, 43% inhibition
p-chloromercuribenzoate
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0.1 mM, 17% inhibition
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.07 - 0.45
Butanoyl-CoA
0.00714
butyryl-CoA
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0.0025 - 0.05
decanoyl-CoA
0.0025 - 0.05
Dodecanoyl-CoA
0.0034
electron transfer flavoprotein
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0.0099 - 0.069
ferrocenium hexafluorophosphate
0.0144
furylpropionyl-CoA
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0.0013 - 0.002
hexadecanoyl-CoA
0.0014 - 0.0216
Hexanoyl-CoA
0.0087
indolepropionyl-CoA
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0.00021
linoleoyl-CoA
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0.001 - 0.012
Octanoyl-CoA
0.00007
palmitoleoyl-CoA
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0.0008 - 0.023
palmitoyl-CoA
1.67
phenazine methosulfate
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0.0023 - 0.0055
tetradecanoyl-CoA
0.01
tetradecenoyl-CoA
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0.0563
valeryl-CoA
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0.0426
[4-(dimethylamino)phenyl]propionyl-CoA
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
8.33 - 11.5
Butanoyl-CoA
0.233 - 11.7
decanoyl-CoA
7
dodecadecanoyl-coA
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3.33 - 9.5
Dodecanoyl-CoA
13.6
furylpropionyl-CoA
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0.617 - 2.92
hexadecanoyl-CoA
2.83 - 16.8
Hexanoyl-CoA
3.4
indolepropionyl-CoA
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-
0.667
Octadecanoyl-CoA
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K304E mutant enzyme, ferricenium assay
0.0024 - 19.2
Octanoyl-CoA
1.67 - 18.3
recombinant beta-Y16L electron transferring flavoprotein
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1 - 14.7
recombinant electron transferring flavoprotein
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2.67 - 8.33
tetradecanoyl-CoA
4.6
[4-(dimethylamino)phenyl]propionyl-CoA
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00036
2-octynoyl-CoA
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competitive vs. indolepropionyl-CoA
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.46
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substrate indolepropionyl-CoA, ferrocenium hexafluorophosphate as electron carrier
6.75
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17.5
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recombinant K304E mutant enzyme, measured with ferricenium assay
24.9
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recombinant wild-type enzyme, measured with ferricenium assay
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
9 - 10
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T168A mutant
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 10
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T168A mutant enzyme, approx. 20% of maximum activity at pH 6.0, sigmoidal increase between pH 5.5 and pH 9.0, approx. 80% of maximal activity at pH 7.8
6 - 9.5
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7 - 10
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approx. 20% of maximum activity at pH 7.5, sigmoidal increase between pH 7.0 and pH 10.0, approx. 80% of maximal activity at pH 9.0
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
43000
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4 * 43000, recombinant enzyme, SDS-PAGE
44000
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4 * 44000, SDS-PAGE
119000
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gel filtration
178000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
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gel filtration, 64800, predicted by 37-amino acid leader peptide cleaved sequentially by two mitochondrial peptidases
tetramer
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
molecular dynamics simulation and comparison between the porcine MCAD and human MCAD structures. Both proteins are essentially similar
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wild-type and E376G/T255E double mutant enzyme and enzyme substrate complexes, vapor diffusion method at 4°C using the sitting drop technique, 0.027 mg enzyme in 140 mM Tris-acetate, pH 7.0, 8% w/v polyethylene glycol 4000, the human enzyme structure is essentially the same as that of the pig enzyme
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0 - 37
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biphasic inactivation, half-lives: 3 h, fast phase, and more than 700 h, slow phase, at 28°C and 2 h, fast phase, and approx. 230 h, slow phase, at 37°C for the wild-type enzyme, the corresponding values for the K304E mutant enzyme are 1.7 h, 100 h at 28°C and 1.25 h and 55 h at 37°C
25
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mutant enzyme E376Q is instable at 25°C
37
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60 min, bout 20% resudal activity
44.5
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melting temperature, mutant Y158H
50
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melting temperature, mutant R206C
52
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melting temperature, mutant A52V; melting temperature, mutant R413S
52.5
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melting temperature, mutant Y67H
53.5
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melting temperature, mutant D266G; melting temperature, mutant R334K
54
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melting temperature, mutant K329E
56.5
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melting temperature, wild-type
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
affinity-purified, ca. 95% pure
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recombinant liver enzyme, DEAE-Sephacel, hydroxyapatite, tandem column-chromatography
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recombinant T168A mutant enzyme
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recombinant wild-type and K304E mutant enzyme
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recombinant wild-type, T255E, T255E/E367G and T255E/E367T mutant enzymes
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wild-type and E376G/T255E double mutant enzyme
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
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expression in Escherichia coli
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expression of recombinant wild-type and K304E mutant enzyme in Escherichia coli
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expression of T168A mutant enzyme in Escherichia coli
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gene ACADM, DNA and amino acid sequence determination and analysis
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heterologous expression of wild-type, K304E and R28C mutant enzymes from patients with medium chain acyl-CoA dehydrogenase deficiency, in Escherichia coli and COS-7 cells
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in vitro translation in rabbit reticulocyte lysate
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A1010C
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genotype, the naturally occuring mutation is involved in medium-chain acyl-CoA dehydrogenase deficiency
A151T
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the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
A293E
-
less than 5% residual octanoyl-CoA oxidation activity
A52V
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mutation identified in a newborn. Mutatio lowers the temperature threshold at which loss-of-function occurs
A533C
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genotype, the naturally occuring mutation is involved in medium-chain acyl-CoA dehydrogenase deficiency
D221N
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less than 5% residual octanoyl-CoA oxidation activity
D266G
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mutation identified in a newborn. Mutatio lowers the temperature threshold at which loss-of-function occurs
D320Y
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less than 5% residual octanoyl-CoA oxidation activity
D79X
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the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
delT125, E126
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less than 5% residual octanoyl-CoA oxidation activity
E376G
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the rate of dehydrogenation is lowered by approximately 5 orders of magnitude
E376Q/E99G
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the rate of dehydrogenation is lowered by 4-5 orders of magnitude
F194S
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less than 5% residual octanoyl-CoA oxidation activity
G127A
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genotype, the naturally occuring mutation is involved in medium-chain acyl-CoA dehydrogenase deficiency, not clearly associated with a clinical phenotype
G170R
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the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
G242R
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less than 5% residual octanoyl-CoA oxidation activity
G285R
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the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
G799A
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genotype, the naturally occuring mutation is involved in medium-chain acyl-CoA dehydrogenase deficiency
I208T
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about 5% residual octanoyl-CoA oxidation activity
K153T
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less than 5% residual octanoyl-CoA oxidation activity
K276X
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less than 5% residual octanoyl-CoA oxidation activity
L59F
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the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
L73DELTA
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the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
M303V
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less than 5% residual octanoyl-CoA oxidation activity
N169D
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the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
N354K
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about 8% residual octanoyl-CoA oxidation activity
N396Y
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involved in MCAD deficiency with a MCAD activity of 11.2% compared to the wild type enzyme, in combination with the deletion mutation DELTA449-CTGA-452
P128X
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the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
Q20R
-
the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
R123K
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the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
R206C
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mutation identified in a newborn. Mutatio lowers the temperature threshold at which loss-of-function occurs
R256S
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the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
R334K
-
mutation identified in a newborn. Mutatio lowers the temperature threshold at which loss-of-function occurs
R413S
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mutation identified in a newborn. Mutatio lowers the temperature threshold at which loss-of-function occurs
R6H
-
about 45% residual octanoyl-CoA oxidation activity
T1229G
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genotype, the naturally occuring mutation is involved in medium-chain acyl-CoA dehydrogenase deficiency
T168A
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thermostability is markedly decreased, 80% lowered activity in ferricinum assay
T199C
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genotype, the naturally occuring mutation is involved in medium-chain acyl-CoA dehydrogenase deficiency, not clearly associated with a clinical phenotype
T255E
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same activity with octanoyl-CoA as wild-type, activity/chain length profile is, however, narrower
T255E/E376G
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chimeric medium-long chain acyl-CoA dehydrogenase, has 20% of the activity of medium-chain acyl-CoA dehydrogenase and 25% that of long-chain acyl-CoA dehydrogenase activity with its best substrates octanoyl-CoA and dodecanoyl-CoA respectively, activity maximum is shifted to C12 and C14-CoA, enzyme shows an enhanced rate of reoxidation with oxygen
T255E/E376T
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shifts the chain length activity profile to higher values, drastic reduction of maximal velocity
T92T
-
the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
T96I
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the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
V247A
-
less than 5% residual octanoyl-CoA oxidation activity
V362V
-
the mutation is involved in medium chain acyl-CoA dehydrogenase deficiency
Y158H
-
mutation identified in a newborn. Mutatio lowers the temperature threshold at which loss-of-function occurs
Y312S
-
about 8% residual octanoyl-CoA oxidation activity
Y394X
-
less than 5% residual octanoyl-CoA oxidation activity
Y67H
-
mutation identified in a newborn. Mutatio lowers the temperature threshold at which loss-of-function occurs
additional information
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among 11 Japanese patients with medium-chain acyl-CoA dehydrogenase deficiency, mutation c.449-452delCTGA accounts for 45%. Seven of 10 independent patients carried at least one copy of the mutation. Phenotypes of homozygous patients with the c.449-452delCTGA mutation varied from asymtomatic to life-threatening metabolic decompensations
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
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application of single exon and multiplex PCR protocol for sequencing based mutation screening of medium-chain acyl-CoA dehydrogenase and ornithine transcarbamylase genes. Both protocols give comparable resultswithout any re-design of the PCR primers or other optimization steps
medicine
additional information
-
highly homologous to human very-long-chain acyl-CoA dehydrogenase