Information on EC 6.3.2.11 - carnosine synthase

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The expected taxonomic range for this enzyme is: Tetrapoda

EC NUMBER
COMMENTARY hide
6.3.2.11
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RECOMMENDED NAME
GeneOntology No.
carnosine synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + L-histidine + beta-alanine = ADP + phosphate + carnosine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxamide formation
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-
-
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carboxylic acid amide formation
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-
-
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peptide synthase reaction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
carnosine biosynthesis
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homocarnosine biosynthesis
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Arginine and proline metabolism
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Histidine metabolism
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beta-Alanine metabolism
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SYSTEMATIC NAME
IUBMB Comments
L-histidine:beta-alanine ligase (ADP-forming)
This enzyme was thought to form AMP [1,2], but studies with highly purified enzyme proved that it forms ADP [4]. Carnosine is a dipeptide that is present at high concentrations in skeletal muscle and the olfactory bulb of vertebrates [3]. It is also found in the skeletal muscle of some invertebrates. The enzyme can also catalyse the formation of homocarnosine from 4-aminobutanoate and L-histidine, with much lower activity [4].
CAS REGISTRY NUMBER
COMMENTARY hide
9023-61-4
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
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histidine-containing dipeptides like carnosine and anserine have protective functions in both health and disease. Carnosine is synthesized by the enzyme carnosine synthase (CARNS), which is present in skeletal and heart muscle, as well as in certain regions in the brain and kidney
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 1,2,4-triazole-3-Ala + beta-Ala
AMP + phosphate + beta-Ala-1,2,4-triazole-3-alanine
show the reaction diagram
ATP + 1-methylhistidine + beta-Ala
AMP + phosphate + beta-Ala-1-methylhistidine
show the reaction diagram
ATP + 2,6-diaminopimelate + beta-Ala
AMP + phosphate + beta-Ala-2,6-diaminopimelate
show the reaction diagram
-
-
-
-
ATP + 2-imidazole-3-Ala + beta-Ala
AMP + phosphate + beta-Ala-2-imidazole-3-Ala
show the reaction diagram
ATP + 2-methyl-L-His + beta-Ala
AMP + phosphate + beta-Ala-2-methyl-L-His
show the reaction diagram
-
-
i.e. ophidine
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ATP + 3-methylhistidine + beta-Ala
AMP + phosphate + beta-Ala-3-methylhistidine
show the reaction diagram
ATP + 5-hydroxylysine + beta-Ala
AMP + phosphate + beta-Ala-5-hydroxylysine
show the reaction diagram
ATP + Arg + beta-Ala
AMP + phosphate + beta-Ala-Arg
show the reaction diagram
ATP + DL-2-amino-6-hydroxyoctanoate + beta-Ala
AMP + phosphate + beta-Ala-DL-2-amino-6-hydroxyoctanoate
show the reaction diagram
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-
-
-
ATP + DL-His-DL-His + beta-Ala
AMP + phosphate + beta-Ala-DL-His-DL-His
show the reaction diagram
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-
-
-
ATP + L-canavanine + beta-Ala
AMP + phosphate + beta-Ala-L-canavanine
show the reaction diagram
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-
-
-
ATP + L-His + 2,3-diaminopropanoate
AMP + phosphate + 2,3-diaminopropanoyl-L-His
show the reaction diagram
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-
-
-
-
ATP + L-His + 2,4-diaminobutanoate
AMP + phosphate + 2,4-diaminobutanoyl-L-His
show the reaction diagram
ATP + L-His + 3-amino-n-butanoate
AMP + phosphate + beta-n-aminobutanoyl-L-His
show the reaction diagram
ATP + L-His + 3-aminoisobutanoate
AMP + phosphate + 3-aminoisobutanoyl-L-His
show the reaction diagram
ATP + L-His + 4-aminobutanoate
AMP + phosphate + homocarnosine
show the reaction diagram
ATP + L-His + 5-aminopentanoate
AMP + phosphate + 5-aminopentanoyl-L-His
show the reaction diagram
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-
-
-
-
ATP + L-His + 6-aminooctanoate
AMP + phosphate + 6-aminooctanoyl-L-His
show the reaction diagram
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-
-
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ATP + L-His + beta-Ala
ADP + phosphate + carnosine
show the reaction diagram
ATP + L-histidine + 4-aminobutanoate
ADP + phosphate + homocarnosine
show the reaction diagram
ATP + L-histidine + beta-alanine
ADP + phosphate + carnosine
show the reaction diagram
ATP + L-lysine + beta-alanine
ADP + phosphate + ?
show the reaction diagram
ATP + L-ornithine + beta-alanine
ADP + phosphate + ?
show the reaction diagram
ATP + Lys + beta-Ala
AMP + phosphate + beta-Ala-Lys
show the reaction diagram
ATP + N-pi-methylhistidine + beta-alanine
ADP + phosphate + ?
show the reaction diagram
ATP + Orn + beta-Ala
AMP + phosphate + beta-Ala-Orn
show the reaction diagram
CTP + L-His + beta-Ala
CMP + phosphate + carnosine
show the reaction diagram
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-
-
-
ITP + L-His + 4-aminobutanoate
IMP + phosphate + homocarnosine
show the reaction diagram
-
-
-
-
L-histidine + beta-alanine + ATP
carnosine + AMP + diphosphate
show the reaction diagram
-
-
-
?
additional information
?
-
-
ATP-diphosphate exchange
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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
ATP + L-His + beta-Ala
ADP + phosphate + carnosine
show the reaction diagram
-
the concentration of histidine in muscle and plasma is high relative to its Km with muscle carnosine synthase, whereas beta-alanine exists in low concentration in muscle and has a higher Km with muscle carnosine synthase, which indicates that it is the availability of beta-alanine that is limiting to the synthesis of carnosine in skeletal muscle
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-
?
ATP + L-histidine + beta-alanine
ADP + phosphate + carnosine
show the reaction diagram
-
-
-
-
?
L-histidine + beta-alanine + ATP
carnosine + AMP + diphosphate
show the reaction diagram
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-Diaminodecane
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10 mM, 43% loss of activity
1,8-diaminooctane
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10 mM, 27% loss of activity
1-methylhistidine
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synthesis of carnosine
2-Aminoethylphosphonic acid
3-Aminopropane sulfonic acid
3-Aminopropanephosphonic acid
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-
3-methylhistidine
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synthesis of carnosine
5-Aminopentanoate
5-Aminopentanol
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10 mM, 11% loss of activity
6-Aminohexanol
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10 mM, 10% loss of activity
alpha-Methyl-dopa
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Aminoethanol
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10 mM, 17% loss of activity
Aminooxyacetate
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chlorpromazine
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0.1 mM stimulates, 1 mM inhibits 45%
diphosphate
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dithiothreitol
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Fe2+
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weak
iodoacetamide
K+
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10-100 mM, weak inhibition
Mo2+
-
weak
n-butylamine
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10 mM, 15% loss of activity
n-Hexylamine
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10 mM, 34% loss of activity
n-octylamine
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10 mM, 58% loss of activity
Nipecotic acid
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norepinephrine
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O-Phosphoethanolamine
phosphate
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spermidine
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
chlorpromazine
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0.1 mM stimulates, 1 mM inhibits 45%
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.35 - 18.2
4-aminobutanoate
0.19 - 0.57
ATP
1.01 - 1.8
beta-Ala
0.033 - 0.46
beta-Alanine
0.0166 - 0.0185
L-His
0.1 - 0.37
L-histidine
1.42 - 4.67
L-lysine
0.52 - 7.66
L-ornithine
0.39 - 24.7
N-pi-methylhistidine
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.05 - 0.44
4-aminobutanoate
0.002 - 0.032
ATP
1.16 - 6.03
beta-Alanine
0.004 - 0.055
L-histidine
0.0002 - 0.004
L-lysine
0.0001 - 0.0066
L-ornithine
0.0001 - 0.015
N-pi-methylhistidine
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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activity in muscle is higher after exercise, which may lead to an increase of the L-carnosine levels in plasma
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.3
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7.4
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carnosine synthesis
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.3 - 8.5
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6.3: about 70% of maximal activity, 8.5: about 55% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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primary kidney cells
Manually annotated by BRENDA team
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primarily in proximal tubules, CARNS is expressed in glomeruli and tubular cells, close to the apical membrane
Manually annotated by BRENDA team
additional information
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carnosine-synthesizing and carnosine-hydrolyzing enzymes are localized in distinct compartments in the nephron, enzyme localization study, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
traces
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
100000
SDS-PAGE
119000
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2 * 119000, SDS-PAGE
250000
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gel filtration
430000
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 100000, SDS-PAGE
dimer
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2 * 119000, SDS-PAGE
tetramer
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 8
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stable in the range
1000
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dithiothreitol stabilizes
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most of the activity is lost upon freezing or upon dialysis with EDTA-treated cellophan tubing for several h at 0°C
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pH 7.0, 25°C, 1 h, with crystalline ribonuclease, not significantly inactivated
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-10°C, as a lyophilized powder, 25% loss of activity
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
affinity chromatography
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partial, using ammonium sulfate precipitation
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in HEK-293T cells