Information on EC 2.7.8.41 - cardiolipin synthase (CMP-forming)

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

EC NUMBER
COMMENTARY hide
2.7.8.41
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RECOMMENDED NAME
GeneOntology No.
cardiolipin synthase (CMP-forming)
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
a CDP-diacylglycerol + a phosphatidylglycerol = a cardiolipin + CMP
show the reaction diagram
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-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
cardiolipin and phosphatidylethanolamine biosynthesis (Xanthomonas)
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cardiolipin biosynthesis II
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cardiolipin biosynthesis
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Glycerophospholipid metabolism
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
CDP-diacylglycerol:L-1-phosphatidyl-glycerol diacylglycerolphosphotransferase (CMP-forming)
The eukaryotic enzyme is involved in the biosynthesis of the mitochondrial phospholipid cardiolipin. It requires divalent cations for activity.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
a CDP-diacylglycerol + a phosphatidyl-glycerol
a cardiolipin + CMP
show the reaction diagram
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
show the reaction diagram
a phosphatidylglycerol + a phosphatidylglycerol
a cardiolipin + glycerol
show the reaction diagram
Cafeteria sp.
-
-
-
-
?
CDP-1,2-dimyristoylglycerol + egg yolk phosphatidylglycerol
a cardiolipin + CMP
show the reaction diagram
-
-
-
-
?
CDP-dimyristoylglycerol + 1,2-dioleoylphosphatidylglycerol
1-(1-myristoyl-2-myristoyl-sn-glycero-3-phospho)-3-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
show the reaction diagram
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competition experiments with [14C]-CDP-dioleoylglycerol show that the enzyme has similar activity with CDP-dimyristoylglycerol, CDP-diacylglycerol from egg yolk and CDP-dioleoylglycerol. CDP-dipalmitoylglycerol shows considerably less activity
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-
?
CDP-dimyristoylglycerol + egg yolk phosphatidylglycerol
cardiolipin + CMP
show the reaction diagram
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-
-
-
?
CDP-dioleoylglycerol + 1,2-dilinoleoylphosphatidylglycerol
1-(1-linoleoyl-2-linoleoyl-sn-glycero-3-phospho)-3-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
show the reaction diagram
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the enzyme is more active with dioleoyl and dilinoleoyl species of phosphatidylglycerol than with species with one or two palmitoyl groups
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-
?
CDP-dioleoylglycerol + 1,2-dimyristoylphosphatidylglycerol
1-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-3-(1-myristoyl-2-oleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
show the reaction diagram
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dimyristoyl phosphatidylglycerol is a very poor substrate
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-
?
CDP-dioleoylglycerol + 1,2-dioleoylphosphatidylglycerol
1,3-bis(1,2-dioleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
show the reaction diagram
CDP-dioleoylglycerol + 1,2-dipalmitoylphosphatidylglycerol
1-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-3-(1-palmitoyl-2-palmitoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
show the reaction diagram
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the enzyme is more active with dioleoyl and dilinoleoyl species of phosphatidylglycerol than with species with one or two palmitoyl groups
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-
?
CDP-dioleoylglycerol + 1-oleoyl-2-linoleoyl phosphatidylglycerol
1-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-3-(1-oleoyl-2-linoleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
show the reaction diagram
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the enzyme is more active with dioleoyl and dilinoleoyl species of phosphatidylglycerol than with species with one or two palmitoyl groups
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-
?
CDP-dioleoylglycerol + 1-palmitoyl-2-oleoyl phosphatidylglycerol
1-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-3-(1-palmitoyl-2-oleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
show the reaction diagram
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the enzyme is more active with dioleoyl and dilinoleoyl species of phosphatidylglycerol than with species with one or two palmitoyl groups
-
-
?
CDP-dioleoylglycerol + dioleoylphosphatidylglycerol
a cardiolipin + CMP
show the reaction diagram
the enzyme is less active with phosphatidyl-glycerol species carrying one or two palmitoyl groups than with the dioleoyl species of phosphatidyl-glycerol. In addition, CDP-dipalmitoylglycerol hardly competes with CDP-dioleolyglycerol as substrate
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-
?
CDP-dioleoylglycerol + dipalmitoylphosphatidylglycerol
a cardiolipin + CMP
show the reaction diagram
the enzyme is less active with phosphatidyl-glycerol species carrying one or two palmitoyl groups than with the dioleoyl species of phosphatidyl-glycerol. In addition, CDP-dipalmitoylglycerol hardly competes with CDP-dioleolyglycerol as substrate
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-
?
CDP-dipalmitoylglycerol + 1,2-dioleoylphosphatidylglycerol
1-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-3-(1-palmitoyl-2-palmitoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
show the reaction diagram
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competition experiments with [14C]-CDP-dioleoylglycerol show that the enzyme has similar activity with CDP-dimyristoylglycerol, CDP-diacylglycerol from egg yolk and CDP-dioleoylglycerol. CDP-dipalmitoylglycerol shows considerably less activity
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-
?
egg yolk CDP-diacylglycerol + 1,2-dioleoylphosphatidylglycerol
a cardiolipin + CMP
show the reaction diagram
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CDP-diacylglycerol from egg lecithin is primarily CDP-1-palmitoyl-2-oleoylglycerol. Competition experiments with [14C]-CDP-dioleoylglycerol show that the enzyme has similar activity with CDP-dimyristoylglycerol, CDP-diacylglycerol from egg yolk and CDP-dioleoylglycerol. CDP-dipalmitoylglycerol shows considerably less activity
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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
a CDP-diacylglycerol + a phosphatidyl-glycerol
a cardiolipin + CMP
show the reaction diagram
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
show the reaction diagram
a phosphatidylglycerol + a phosphatidylglycerol
a cardiolipin + glycerol
show the reaction diagram
Cafeteria sp.
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-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CoCl2
requires divalent cations for activity. Highest activities are measured in the presence of 20 mM MnCl2, while MgCl2 or CoCl2 stimulate the activity only slightly
KCl
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requires KCl concentration of about 0.4 M
MgCl2
requires divalent cations for activity. Highest activities are measured in the presence of 20 mM MnCl2, while MgCl2 or CoCl2 stimulate the activity only slightly
MnCl2
requires divalent cations for activity. Highest activities are measured in the presence of 20 mM MnCl2, while MgCl2 or CoCl2 stimulate the activity only slightly
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,2-dioleoylphosphatidylglycerol
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above 0.65 mM
CDP-dioleoylglycerol
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above 0.1 mM
EDTA
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20 mM, loss of activity
Triton X-100
0.2 mM, 50% inhibition. Concentrations higher than 0.6 mM result in an almost complete inhibition
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Triton
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maximal activity is obtained with a Triton X-100:phospholipid ratio of 1:1
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1
1,2-dioleoylphosphatidylglycerol
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pH 9.0, 45C
0.0024 - 0.0029
CDP-1,2-dimyristoylglycerol
0.0016
CDP-dimyristoylglycerol
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pH 8.5, 37C, at optimal concentration of phospholipid activators
0.0014 - 0.036
CDP-dioleoylglycerol
0.15
dioleoylphosphatidylglycerol
pH 8.8, 30C
0.032 - 0.0619
egg yolk phosphatidylglycerol
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additional information
additional information
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the two Km values for CDP-diacylglycerol, each estimated by nonlinear regression analysis of 18 kinetic points, are 0.02 and 0.03 mol% in the presence of 1 mM and 10 mM Mg2+ respectively, pH 9.0, 37C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000000373
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pH and temperature not specified in the publication, activity in liver mitochondria
0.000000568
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pH and temperature not specified in the publication, activity in thyroxine-treated liver mitochondria
0.0000029
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at low Co2+ concentration, pH 9.0, 37C
0.0000041
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at high Co2+ concentration, pH 9.0, 37C
0.000513
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pH 9.0, 37C
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 8.5
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pH 6.5: aboput 40% of maximal activity, pH 8.5: about 60%& of maximal activity
7.2 - 8.9
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pH 7.2: about 40% of maximal activity, pH 8.9: about 75% of maximal activity
7.5 - 10
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pH 7.5: about 45% of maximal activity, pH 10.0: about 85% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35 - 65
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35C: about 45% of maximal activity, 65C: about 40% of maximal activity
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 5
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isoelectric point
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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very low
Manually annotated by BRENDA team
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highly expressed
Manually annotated by BRENDA team
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very low
Manually annotated by BRENDA team
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moderate level
Manually annotated by BRENDA team
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highly expressed
Manually annotated by BRENDA team
additional information
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the hCLS1 gene is predominantly expressed in tissues that require high levels of mitochondrial activities for energy metabolism
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
28000
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x * 28000, the functional enzyme is a large complex, the 28000 Da protein forms an oligomeric complex whose biogenesis and/or activity is influenced by the assembly of cytochrome oxidase, SDS-PAGE
32000
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x * 32000, SDS-PAGE
50000
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1 * 50000, SDS-PAGE
60000
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gel filtration
70000
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gel filtration
240000
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radiation inactivation analysis
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
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1 * 50000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
the preprotein expressed in yeast can be imported into mitochondria and processed to a catalytically active protein
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55
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20 min, stable up to
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
after CDP-diacylglycerol affinity chromatography the enzyme is very unstable to freeze-thaw cycles
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80C, stable for a few days, after CDP-diacylglycerol affinity chromatography
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partial
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
CLS_cap, DNA and amino acid sequence determination and analysis, phylogenetic analysis, overview
CLS_pld, phylogenetic analysis, overview
Cafeteria sp.
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expression in COS-7 cells
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expression in reticulocyte lysates or insect cells
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expression of Sco1389 in a cardiolipin-deficient Rhizobium etli mutant
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gene CrCLS1, DNA and amino acid sequence determination and analysis, sequence comparisons, quantitative RT-PCR expression analysis, the gene cannot perform functional complementation of pgsA, a PGPS mutant of Synechocystis sp. PCC6803, but of DELTAcrd1, a CLS mutant of Saccharomyces cerevisiae
generation of transgenic mice selectively expressing human cardiolipin synthase 1 in cardiomyocytes
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overexpression in Escherichia coli
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
CRD1 levels are 7- to 10-fold greater in stationary than in logarithmic growth phase. Expression is somewhat elevated during growth in glycerol/ethanol versus glucose media. CRD1 expression is controlled by factors affecting mitochondrial development, but not by the phospholipid precursors inositol and choline
lipopolysaccharide treatment of HepG2 cells transiently expressing a histidine-tagged human cardiolipin synthase-1 (hCLS1) reduces hCLS1 mRNA and newly synthesized enzyme activity indicating that lipopolysaccharide inhibits production of newly synthesized hCLS1 via reduction in hCLS1 mRNA
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treatment of mice with lipopolysaccharide results in a 55% decrease in mRNA expression of murine lipopolysaccharide compared to controls, but enzyme activity is unaltered
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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cardiolipin synthase as a therapeutic target to attenuate mitochondrial dysfunction in diabetic myocardium