Information on EC 2.3.1.137 - carnitine O-octanoyltransferase

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The expected taxonomic range for this enzyme is: Opisthokonta

EC NUMBER
COMMENTARY hide
2.3.1.137
-
RECOMMENDED NAME
GeneOntology No.
carnitine O-octanoyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
octanoyl-CoA + L-carnitine = CoA + L-octanoylcarnitine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acyl group transfer
SYSTEMATIC NAME
IUBMB Comments
octanoyl-CoA:L-carnitine O-octanoyltransferase
Acts on a range of acyl-CoAs, with optimal activity with C6 or C8 acyl groups. cf. EC 2.3.1.7 (carnitine O-acetyltransferase) and EC 2.3.1.21 (carnitine O-palmitoyltransferase).
CAS REGISTRY NUMBER
COMMENTARY hide
39369-19-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
pigeon
-
-
Manually annotated by BRENDA team
Mus musculus NMRI/Bom
NMRI/Bom strain
-
-
Manually annotated by BRENDA team
Mus musculus Sv/129
strain Sv/129
-
-
Manually annotated by BRENDA team
no activity in Saccharomyces cerevisiae
-
-
-
Manually annotated by BRENDA team
rabbit
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
-
-
Manually annotated by BRENDA team
Wistar
-
-
Manually annotated by BRENDA team
Rattus norvegicus Wistar/Moell
Wistar/Moell
-
-
Manually annotated by BRENDA team
pig
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
overexpression and knock-down of the enzyme gene in a model of hepatic cells. Increase in enzymic activity induces a decrease in medium chain fatty acid and very long chaichain fatty acid levels in the cell. These changes are accompanied by an increase in the level of mRNA encoding enzymes of the peroxisomal beta oxidation, while there is no change in mitochondrial function. A decrease in carnitine ocatanoyltransferase activity has the opposite effect. Results suggest that carnitine ocatanoyltransferase activity, by controlling the peroxisomal amount of medium chain acyls, may control the peroxisomal oxidative pathway
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3-hydroxy-3-methylglutaryl-CoA + L-carnitine
3-hydroxy-3-methylglutaryl-L-carnitine + CoA
show the reaction diagram
-
-
-
-
r
3-methylglutaryl-CoA + L-carnitine
3-methylglutaryl-L-carnitine + CoA
show the reaction diagram
-
little capacity to use this substrate
-
-
r
3-methylglutaryl-L-carnitine + CoA
3-methylglutaryl-CoA + L-carnitine
show the reaction diagram
-
-
-
-
r
4,8-dimethylnonanoyl-CoA + L-carnitine
4,8-dimethylnonanoyl-L-carnitine + CoA
show the reaction diagram
-
-
-
r
4,8-dimethylnonanoyl-L-carnitine + CoA
4,8-dimethylnonanoyl-CoA + L-carnitine
show the reaction diagram
-
-
-
r
acetoacetyl-CoA + L-carnitine
acetoacetyl-L-carnitine + CoA
show the reaction diagram
-
-
-
-
r
acetoacetyl-L-carnitine + CoA
acetoacetyl-CoA + L-carnitine
show the reaction diagram
-
-
-
-
r
acetyl-CoA + L-carnitine
acetyl-L-carnitine + CoA
show the reaction diagram
acetyl-CoA + L-carnitine
CoA + acetyl-carnitine
show the reaction diagram
acetyl-CoA + L-carnitine
CoA + L-acetylcarnitine
show the reaction diagram
acetyl-L-carnitine + CoA
acetyl-CoA + L-carnitine
show the reaction diagram
acyl-CoA + L-carnitine
acyl-L-carnitine + CoA
show the reaction diagram
acyl-L-carnitine + CoA
acyl-CoA + L-carnitine
show the reaction diagram
beta-hydroxy-beta-methylglutaryl-L-carnitine + CoA
beta-hydroxy-beta-methylglutaryl-CoA + L-carnitine
show the reaction diagram
-
-
-
-
r
butanoyl-CoA + L-carnitine
CoA + L-butanoylcarnitine
show the reaction diagram
-
-
-
-
?
butyryl-CoA + L-carnitine
butyryl-L-carnitine + CoA
show the reaction diagram
-
-
-
-
r
butyryl-L-carnitine + CoA
butyryl-CoA + L-carnitine
show the reaction diagram
-
-
-
-
r
choline + L-carnitine
?
show the reaction diagram
decanoyl-CoA + L-carnitine
CoA + L-decanoylcarnitine
show the reaction diagram
-
best substrate
-
-
?
decanoyl-CoA + L-carnitine
L-decanoyl-L-carnitine + CoA
show the reaction diagram
decanoyl-L-carnitine + CoA
decanoyl-CoA + L-carnitine
show the reaction diagram
dodecanoyl-CoA + L-carnitine
CoA + L-dodecanoylcarnitine
show the reaction diagram
-
-
-
-
?
dodecanoyl-CoA + L-carnitine
L-dodecanoyl-L-carnitine + CoA
show the reaction diagram
dodecanoyl-L-carnitine + CoA
dodecanoyl-CoA + L-carnitine
show the reaction diagram
heptanoyl-CoA + L-carnitine
L-heptanoyl-L-carnitine + CoA
show the reaction diagram
heptanoyl-L-carnitine + CoA
heptanoyl-CoA + L-carnitine
show the reaction diagram
hexadecanoyl-CoA + L-carnitine
CoA + L-hexadecanoylcarnitine
show the reaction diagram
-
low activity
-
-
?
hexadecanoyl-CoA + L-carnitine
L-hexadecanoyl-L-carnitine + CoA
show the reaction diagram
hexadecanoyl-L-carnitine + CoA
hexadecanoyl-CoA + L-carnitine
show the reaction diagram
hexanoyl-CoA + L-carnitine
CoA + L-hexanoylcarnitine
show the reaction diagram
-
best substrate
-
-
?
hexanoyl-CoA + L-carnitine
L-hexanoyl-L-carnitine + CoA
show the reaction diagram
hexanoyl-L-carnitine + CoA
hexanoyl-CoA + L-carnitine
show the reaction diagram
L-carnitine + octanoyl-CoA
octanoyl-L-carnitine + CoA
show the reaction diagram
malonyl-CoA + L-carnitine
malonyl-L-carnitine + CoA
show the reaction diagram
-
-
-
-
r
malonyl-L-carnitine + CoA
malonyl-CoA + L-carnitine
show the reaction diagram
-
-
-
-
r
myristoyl-CoA + L-carnitine
myristoyl-L-carnitine + CoA
show the reaction diagram
-
-
-
-
r
myristoyl-L-carnitine + CoA
myristoyl-CoA + L-carnitine
show the reaction diagram
-
-
-
-
r
octanoyl-CoA + L-carnitine
CoA + L-octanoylcarnitine
show the reaction diagram
octanoyl-L-carnitine + CoA
L-carnitine + octanoyl-CoA
show the reaction diagram
palmitoyl-CoA + L-carnitine
L-palmitoyl-L-carnitine + CoA
show the reaction diagram
palmitoyl-L-carnitine + CoA
palmitoyl-CoA + L-carnitine
show the reaction diagram
pivaloyl-CoA + L-carnitine
L-pivaloyl-L-carnitine + CoA
show the reaction diagram
-
little capacity to use this substrate
-
-
r
pivaloyl-L-carnitine + CoA
pivaloyl-CoA + L-carnitine
show the reaction diagram
-
-
-
-
r
propionyl-CoA + L-carnitine
CoA + propionyl-carnitine
show the reaction diagram
propionyl-CoA + L-carnitine
propionyl-L-carnitine + CoA
show the reaction diagram
propionyl-L-carnitine + CoA
propionyl-CoA + L-carnitine
show the reaction diagram
tetradecanoyl-CoA + L-carnitine
CoA + L-tetradecanoylcarnitine
show the reaction diagram
valproyl-CoA + L-carnitine
L-valproyl-L-carnitine + CoA
show the reaction diagram
-
little capacity to use this substrate
-
-
r
valproyl-L-carnitine + CoA
valproyl-CoA + L-carnitine
show the reaction diagram
-
-
-
-
r
additional information
?
-
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
acetyl-CoA + L-carnitine
CoA + acetyl-carnitine
show the reaction diagram
acyl-CoA + L-carnitine
acyl-L-carnitine + CoA
show the reaction diagram
acyl-L-carnitine + CoA
acyl-CoA + L-carnitine
show the reaction diagram
L-carnitine + octanoyl-CoA
octanoyl-L-carnitine + CoA
show the reaction diagram
octanoyl-CoA + L-carnitine
CoA + L-octanoylcarnitine
show the reaction diagram
octanoyl-L-carnitine + CoA
L-carnitine + octanoyl-CoA
show the reaction diagram
propionyl-CoA + L-carnitine
CoA + propionyl-carnitine
show the reaction diagram
additional information
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-bromodecanoic acid
-
-
2-bromooctanoic acid
-
-
2-bromopalmitic acid
-
potent inhibitor
2-Bromopalmitoyl-CoA
-
-
Aminocarnitine
-
-
chlorpromazine
-
-
D-carnitine
Dodecanoyl-CoA
etomoxir
-
hypoglycaemia-inducing drug, double mutant H131A/H340A is insensitive to etomoxir
Etomoxiryl-CoA
-
-
hemiacylcarnitinium
-
-
hemicholinium
-
-
hexadecanoyl-CoA
malonyl-CoA
Octanoyl-CoA
palmitoyl-CoA
-
-
tetradecylglycidic acid
-
-
Trypsin
-
-
-
Zn2+
-
inhibits enzyme in reverse direction
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoate)
-
retains its maximum activity when preincubated at pH 7.0 or 8.5
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.155 - 16
acetyl-CoA
0.783
acetyl-L-carnitine
-
-
0.002 - 0.0167
acyl-CoA
0.0948
carnitine
143
choline
-
mutant [Asn505]COT
0.11
CoASH
-
-
0.0002 - 0.794
decanoyl-CoA
8.4
Decanoyl-L-carnitine
-
-
0.036
hexadecanoyl-L-carnitine
-
-
0.102 - 160
L-carnitine
0.015
Octanoyl-CoA
-
-
0.1
octanoylcarnitine
-
-
0.104
palmitoyl lysophosphatidic acid
-
-
0.00046 - 0.6
palmitoyl-CoA
7.4
palmitoyl-L-carnitine
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.367
Octanoyl-CoA
Mus musculus
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.84
D-carnitine
-
-
113
hemiacylcarnitinium
-
-
0.0035 - 0.106
malonyl-CoA
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.072
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 10
-
-
5.5 - 7.5
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
high expression of CRAT
Manually annotated by BRENDA team
skin fibroblast
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
high expression of CRAT
Manually annotated by BRENDA team
additional information
-
low in distal intestine epithelium, distal intestine muscle, brain, heart, lung, spleen, brown and white adipose tissue
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50000 - 55000
-
SDS-PAGE
53000
-
Western blot, polyclonal antibody reaction
59000
-
gel filtration
60000
-
gel filtration
64400
-
SDS-PAGE
70260
-
calculated from cDNA sequence
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 69000, recombinant enzyme, SDS-PAGE
monomer
additional information
-
active site structure and substrate positioning modeling for wild-type and G553M mutant enzymes
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified recombinant His-tagged wild-type and mutants M335V and C323M enzymes free or in complex with octanoylcarnitine, sitting drop vapour diffusion method, 4C, reservoir solution contains 0.1 M HEPES, pH 7.4, 62% v/v 2-methyl-2,4-pentanediol, larger crystals by micro- and macroseeding, cross-seeding of recombinant purified selenomethionine-labeled enzyme, X-ray diffraction structure determination and analysis at 2.0-2.2 A resolution
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
quite unstable, labile in Triton X-100 and octylglucoside, stable in 8 mM CHAPS, 200 mM guanidium chloride and 0.5% Tween 20
-
stable for at least 1 week in 100 mM phosphate buffer with 0.4 M KCl, pH 5.5-7.5
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-18C, can be kept for several months with only moderate loss of activity
-
-20C, freezing causes a 90% loss of activity within 2 days
-
-70C, stable to freezing at for at least 5 months
-
-80C, freezing causes a 90% loss of activity within 2 days
-
20C, 10 mM sodium diphosphate buffer at pH 7.5, stable for months
-
4C, 10 mM sodium diphosphate buffer at pH 7.5, stable for months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partially
-
recombinant enzyme
-
soluble recombinant His-tagged wild-type and selenomethionine-labeled enzyme from Escherichia coli by nickel affinity chromatography
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA clone from a rat liver library, 2 forms of COT in peroxisomes results of the trans-splicing mechanism in pre-mRNAs
-
cDNA cloning by library screening and recombinant expression in Escherichia coli
-
cDNA PCR amplified, cloned in yeast expression vector pEL26 and expressed in Saccharomyces cerevisiae
cloned and expressed in Escherichia coli
expression in HepG2 cell
expression of wild-type and G553M mutant enzymes in an enzyme-deficient Saccharomyces cerevisiae strain
-
overexpression of the His-tagged enzyme in Escherichia coli as soluble protein, expression of enzyme for selenomethionine-labeling in Escherichia coli strain B834(DE3)
pYES2 plasmid containing the wild-type and the double mutant H131A/H340A of COT expressed in Saccharomyces cerevisiae
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
R518N
-
site-directed mutagenesis, mutant shows 1650fold increased Km for L-carnitine, only slightly affected Km for acyl-CoA and kcat compared to the wild-type enzyme
S552A
-
site-directed mutagenesis, mutant shows 17fold increased Km for L-carnitine compared to the wild-type enzyme
S554X
-
site-directed mutagenesis, mutant shows 10fold decreased kcat compared to the wild-type enzyme
C323M
site-directed mutagenesis, crystal structure comparison with the wild-type enzyme, altered acyl-CoA substrate specificity compared to the wild-type enzyme, highly increased specificity for octanoyl-CoA
G553M
site-directed mutagenesis, highly reduced activity with altered acyl-CoA substrate specificity compared to the wild-type enzyme
M335A
site-directed mutagenesis, reduced activity with altered acyl-CoA substrate specificity compared to the wild-type enzyme
M335V
site-directed mutagenesis, crystal structure comparison with the wild-type enzyme, highly reduced activity with altered acyl-CoA substrate specificity compared to the wild-type enzyme
G553M
-
site-directed mutagenesis, the mutant enzyme shows altered substrate specificity: highly reduced activity with medium- and long-chain acyl-CoAs and increased activity with acetyl-CoA and butanoyl-CoA compared to the wild-type enzyme
additional information
-
the carnitine acetyl-transferase, specific for acetyl-CoA/short-chain acyl-CoAs, can be modified to an enzyme with elevated carnitine octanoyltransferase activity by mutation of Met564 to Gly, overview