Ligand citrate

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Basic Ligand Information

Molecular Structure
Picture of citrate (click for magnification)
Molecular Formula
BRENDA Name
InChIKey
C6H8O7
citrate
KRKNYBCHXYNGOX-UHFFFAOYSA-N
Synonyms:
2-hydroxypropane-1,2,3-tricarboxylate, Citric acid, L-Citric acid, Magnesium citrate
Pathway Source
Pathways


Show all pahtways known for Show all BRENDA pathways known for citrate

Roles as Enzyme Ligand

In Vivo Substrate in Enzyme-catalyzed Reactions (36 results)

EC NUMBER
LITERATURE
REACTION DIAGRAM
PROVEN IN VIVO REACTION
ENZYME 3D STRUCTURE
show the reaction diagram
acetyl-CoA + citrate = acetate + (3S)-citryl-CoA
-
show the reaction diagram
ATP + citrate + CoA = ADP + phosphate + (3S)-citryl-CoA
-
show the reaction diagram
ATP + citrate + L-glutamate = ADP + phosphate + beta-citryl-L-glutamate
-
show the reaction diagram
2 ATP + citrate + N6-acetyl-N6-hydroxy-L-lysine + H2O = 2 ADP + 2 phosphate + N2-citryl-N6-acetyl-N6-hydroxy-L-lysine
-
show the reaction diagram
2 ATP + citrate + N6-acetyl-N6-hydroxy-L-lysine + H2O = 2 ADP + 2 phosphate + N2-citryl-N6-acetyl-N6-hydroxy-L-lysine
-
show the reaction diagram
ATP + L-2,3-diaminopropanoate + citrate = AMP + diphosphate + 2-[(L-alanin-3-ylcarbamoyl)methyl]-2-hydroxybutanedioate
-
show the reaction diagram
ATP + N5-[(S)-citryl]-D-ornithine + citrate = AMP + diphosphate + staphyloferrin A
-
show the reaction diagram
ATP + D-ornithine + citrate = AMP + diphosphate + N5-[(S)-citryl]-D-ornithine
-
show the reaction diagram
ATP + citrate + L-glutamate = ADP + phosphate + N-citryl-L-glutamate
-

In Vivo Product in Enzyme-catalyzed Reactions (19 results)

EC NUMBER
LITERATURE
REACTION DIAGRAM
PROVEN IN VIVO REACTION
ENZYME 3D STRUCTURE
show the reaction diagram
acetyl-CoA + oxaloacetate + H2O = citrate + CoA
-
show the reaction diagram
acetyl-CoA + H2O + oxaloacetate = citrate + CoA
-
-
show the reaction diagram
acetyl-CoA + H2O + oxaloacetate = citrate + CoA
-
-
show the reaction diagram
ADP + phosphate + beta-citryl-L-glutamate = ATP + citrate + L-glutamate
-

Substrate in Enzyme-catalyzed Reactions (108 results)

EC NUMBER
LITERATURE
REACTION DIAGRAM
REACTION
ENZYME 3D STRUCTURE
show the reaction diagram
citric acid + NAD+ = ?
-
show the reaction diagram
citric acid + NADPH + ATP = ? + NADP+ + AMP + phosphate
-
show the reaction diagram
S-adenosyl-L-methionine + citrate = S-adenosyl-L-homocysteine + ?
-
show the reaction diagram
citrate = itaconate + CO2
-
show the reaction diagram
citrate = cis-aconitate + H2O
-
show the reaction diagram
ATP + citrate + L-glutamate = ADP + phosphate + beta-citryl-L-glutamate
-
show the reaction diagram
2 ATP + citrate + N6-acetyl-N6-hydroxy-L-lysine + H2O = 2 ADP + 2 phosphate + N2-citryl-N6-acetyl-N6-hydroxy-L-lysine
-
show the reaction diagram
ATP + N-acetyl-L-aspartate + citrate = ?
-
show the reaction diagram
ATP + N5-[(S)-citryl]-D-ornithine + citrate = AMP + diphosphate + staphyloferrin A
-
show the reaction diagram
ATP + D-ornithine + citrate = AMP + diphosphate + N5-[(S)-citryl]-D-ornithine
-
show the reaction diagram
ATP + citrate + L-glutamate = ADP + phosphate + N-citryl-L-glutamate
-

Product in Enzyme-catalyzed Reactions (41 results)

EC NUMBER
LITERATURE
REACTION DIAGRAM
REACTION
ENZYME 3D STRUCTURE
-
show the reaction diagram
Fe(III)-dicitrate + NADPH + H+ = Fe(II) + citrate + NADP+
-
-
show the reaction diagram
acetyl-CoA + H2O + oxaloacetate = 2-hydroxypropane-1,2,3-tricarboxylate + CoA
-
show the reaction diagram
acetyl-CoA + H2O + oxaloacetate = citrate + CoA
-
-
show the reaction diagram
acetyl-CoA + H2O + oxaloacetate = citrate + CoA
-
show the reaction diagram
acetate + oxaloacetate = citrate
-
show the reaction diagram
cis-aconitate + H2O = citrate
-
-
show the reaction diagram
ADP + phosphate + beta-citryl-L-glutamate = ATP + citrate + L-glutamate
-

Enzyme Cofactor/Cosubstrate (3 results)

COMMENTARY
EC NUMBER
LITERATURE
ENZYME 3D STRUCTURE

Activator in Enzyme-catalyzed Reactions (178 results)

COMMENTARY
EC NUMBER
LITERATURE
ENZYME 3D STRUCTURE

Inhibitor in Enzyme-catalyzed Reactions (794 results)

COMMENTARY
EC NUMBER
LITERATURE
ENZYME 3D STRUCTURE
1mM, 48.3% residual activity
-
inhibition is pH-dependent
1 mM, 24% inhibition
-
incubation of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides with Fe2+ and citrate results in rapid O2-dependent inactivation of the enzyme. The Fe(2+)-citrate complex binds to the glucose 6-phosphate binding site and then undergoes reaction with H2O2 formed in solution leading to the oxidative modification of amino acids essential for enzyme activity
-
competitive with respect to oxaloacetate
reduction of oxaloacetate to malate
competitive
competitive, 61% inhibition at 5 mM
-
inhibits all PtNADP-ME activities significantly
-
10 mM
with constant concentrations of isocitrate, NAD+ and Mg2+ up to 10 mM and without AMP, citrate is an activator
30% inhibition at 1 mM and 5 mM
50% inhibition at 1 mM
1 mM, 16% inhibition; 1 mM, 84% decreases in activity
50 mM, pH 5.4, 72% inhibition
-
5 mM, 20% inhibition of NADH linked hydroxypyruvate reduction, 25% of NADPH linked reduction
competitive vs. hydroxypyruvate
5 mM
-
competitive inhibition with respect to 3-hydroxy-3-methylglutaryl-CoA
2 mM, 28% residual activity
-
competitive
-
32% residual activity at 10 mM
-
37% residual activity at 400 mM in cultivar Violetto di Sicilia, 59% residual activity at 200 mM in cultivar Violetto di Provenza, 18% residual activity at 400 mM in cultivar Tema 2000
-
68.92% inhibition at 20 mM
-
complete inhibition at 20 mM, 47% inhibition at 2 mM
-
slight inhibition
-
weak inhibition
-
univalent anion, competitive vs. ascorbate
-
76% inhibition at 5 mM
-
competitive inhibition with respect to 2-oxoglutarate
-
30% inhibition at 5 mM
-
less effective inhibitor
-
modest inhibitor
-
modest inhibitor of ALKHB5
-
92 mM, pH 8, very slight inhibition
-
10% residual activity at 10 mM
12% inhibition at 1 mM, 60% inhibition at 10 mM
24% inhibition at 0.5 mM, 32% inhibition at 5 mM
26% residual activity at 1 mM
27.9% inhibition at 10 mM
30% inhibition at 0.1 mM, 33% inhibition at 10 mM
42.70% inhhibition at 50 mM
65% residual activity at 10 mM
in descending order of inhibition potency: p-hydroxybenzoic acid > glutathione = ascorbic acid > L-cysteine > EDTA > citric acid
noncompetitive inhibition
uncompetitive inhibition, 74.5% inhibition at 10 mM
0.25 mM, 29% inhibition, 50.0 mM, 87% inhibition
-
noncompetitive inhibition
-
slight
-
inhibited by high concentrations, 40 mM
-
67% activity in the presence of 10 mM citrate
-
inhibition of amination, no effect on deamination
-
10 mM, 60% inhibition of oxidative deamination
-
at 6.67 mM 29% inhibition
-
in acid pH range: inhibitor of reduction of 7,8-dihydrofolate but not folate
-
1 mM, about 10% inhibition
-
2.5 mM, 25% inhibition
-
inhibition in decreasing order: fumarate, succinate, citrate, acetate
-
40 mM, 22% residual activity
-
to some extent
inactivation at pH 5.5, Zn2+ protects
-
66.1% residual activity at 10 mM
-
competitive versus 2-oxoglutarate; noncompetitive
-
5 mM, 1% residual activity
50% inhibition at 2.5 mM
competitive
competitive with acetyl-CoA, noncompetitive with oxaloacetate
product inhibition, competitive. Citrate binds tightly to the substrate binding site and its binding induces a compact closed conformation
40% inhibition at 10 mM
-
about 40% residual activity at 10 mM
-
1 mM, 82% residual activity
-
activity can by restored with Mg2+
-
2.5 mM, 82% residual activity
-
3.55% residual activity at 2.5 mM
-
65% residual activity at 10 mM
-
1 mM, 89% inhibition
-
1 mM, 95% inhibition
-
noncompetitive to glucose and ATP
60% inhibition at 1 mM
at physiological concentrations
heart enzyme is more sensitive than liver enzyme
phosphorylation enhances sensitivity
skeletal muscle enzyme is more sensitive than liver enzyme
strong
0.12 mM, 50% inhibition
0.23 and 0.17 mM mM, 50% inhibition at 20° and 6°C, respectively, normoxic turtles, 0.3 mM, 50% inhibition at 20°C and 6°C, anoxic turtles
10 mM, 60% inhibition
10 mM, approx. 30% inhibition
2 mM, complete inhibition
50% inhibition below 0.25 mM
activates the enzyme in the absence of phosphate and inhibits the enzyme in the presence of phosphate
almost complete inhibition at 1 mM citrate in the absence of D-fructose 2,6-bisphosphate
at pH 7.6, not at pH 8.4
cAMP, ADP or fructose 1,6-bisphosphate restore activity
inhibition of M- and C-type PFK in pancreatic beta-cells
isoenzyme PFK2
mild inhibitory effects, but only at concentrations exceeding 2 mM
presence of 12 mM Mg2+ relieves inhibition completely
strong inhibition
strong inhibition; synergistic with ATP; synergistic with NH4+; synergistic with phosphate and AMP
strong inhibition; synergistic with phosphate and AMP
strong inhibition; weak inhibition
the native 85000 Da enzyme is moderately inhibited by citrate, the 49000 Da shorter fragment of PFK1 proves to be completely resistant to inhibition by citrate
weak inhibition
when 5 mM of citrate is added a moderate reduction for about 10–20% is recorded in the homogenate of TE22 and TE23 strain, while in A158 strain much stronger reduction of PFK1 specific activity, for approximately 40% is observed
with glucose 1,6-bisphosphate or fructose 1,6-bisphosphate as activator
slight inhibition
-
1 M, 23% loss of activity
3.5 mM, 55% inhibition
50% inhibition at 18.4 mM
60% inhibition at 5 mM, significant allosteric effector of the partially purified enzyme
74% inhibition at 4 mM, cPK2; 83% inhibition at 4 mM, cPK1; 93% inhibition at 4 mM, cPK3; 97% inhibition at 4 mM, cPK4; 98% inhibition at 4 mM, cPK5
at 5 mM, pH 7.0, 40% inhibition
citrate at 2 mM inhibits GST-tagged PfPYK activity by over 90%, citrate slightly decreases the affinity for the PEP substrate, with no obvious change in the apparent kcat
citrate binds TcoPYK's active site, induces an R-state transition, and is a weak inhibitor of enzyme activity, 30% inhibition at 25 mM
fat body isozyme; weak, flight muscle isozyme
IC50: 9.2 mM at pH 6.4, IC50: 14.2 mM at pH 7.4
isozyme PKI, kinetics; not isozyme PKII
noncompetitive with respect to ADP
potent inhibitor
no inhibition
-
not relieved by Mg2+
-
strong inhibitor of the hypothalamic and the hepatic enzyme after intracerebroventricular injection and during fasting, rats treated with citrate present improved insulin signal transduction in liver, skeletal muscle, and epididymal fat pad, overview, no influence on enzyme expression
-
feedback inhibition
-
40% inhibition at 50 mM
-
a PNPase-mediated response to citrate, and PNPase deletion broadly impacts on the metabolome. PNPase-dependent cells show reduced growth in the presence of increased citrate concentration. In vitro, citrate directly binds and modulates PNPase activity, and the enzyme is inhibited by binding of metal-chelated citrate, predominantly complexed as magnesium-citrate, in the active site at physiological concentrations. In the contrary, metal-free citrate is bound at a vestigial active site, where it stimulates PNPase activity
weak competitive inhibition against succinate
0.167 M, weak
-
plasmalogen-specific PLA2
depressed activity
-
mixed type of inhibition with a change from a hyperbolic velocity curve in absence of citrate to a sigmoidal one in its presence
competitive, both with respect to trehalose phosphate and Mg2+
-
no activity in Tris-citrate and only minimal activity in acetate buffer
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1.4 mM, 30°C, pH 7.5, 68% remaining activity with glycogen synthase D as substrate
40 mM, 30% inhibition of ATP hydrolysis of enzyme from plump seed
inhibits the cardiac enzyme
competitive
-
slight inhibition at 20-100 mM
-
at 0.2 M 50% of initial activity with ssDNA
-
slight inhibition
-
24% inhibition at 6 mM
-
25 mM, 54% inhibition
-
64% inhibition at 5 mM
-
complete inhibition at 5-10 mM, 84.7% inhibition at 1 mM
-
slight inhibition at 200 mg/l
-
36.16% residual activity at 5 mM
-
1%, 42% inhibition
no other organic acids, highest inhibition at low pH
-
about 90% residual activity at 1% (v/v)
-
chelating agent
-
10 mM and 20 mM, 15% inhibition
citrate ions are shown to bind at only three well-defined sites involving both ion pairs and hydrogen bonds. Molecular dynamics simulations evidence that citrate binding has a remarkable conformational influence on the 3D structure of carnosinase, increasing the binding affinity of carnosine to the catalytic site
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partial inhibition
-
weak
-
slight inhibitory effect
-
enzyme from mesenteric lymph nodes
-
competitive inhibition
-
40 mM, 44% inhibition
-
binding of the ligand to the active site involves stabilizing interactions, such as a carboxylate group that binds the nickel ions at the active site and several hydrogen bonds with the surrounding residues
8 mM: 95% of activity compared to H2O
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0.1 mM: 77% inhibition, 1 mM: 98% inhibition
-
0.1 mM: about 30% inhibition, 1 mM: 90% inhibition; inhibitory activity almost completely counteracted by 6 mM of Mn2+: inhibitory effect attributable to chelation of Mn2+
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buffer
-
6 mM
-
20% inhibition at 0.5 mM
-
9 mM
-
competitive
-
0.5 mM inhibitor or 2 mM inhibitor in presence of 10 mM Mn2+, 24% inhibition
-
50% inhibition of mitochondrial enzyme at 4.5 mM
-
74% residual activity at 2 mM
-
about 77% residual activity at 25 mM
-
19% hdc gene expression at 0.8 g/l
-
diminishes hdc gene expression
-
stronger inhibitory effect on strain ATCC 367 than on IOEB 9809
-
1 mM, 86% residual activity
potent inhibitor at pH 7 in absence of glycerol, but its effectiveness is decreased by raising the pH to 8 and/or by adding glycerol
strong inhibition
above 5.0 mM, weak
-
inhibits below pH 4.8
-
50% inhibition at 1.9 mM at 37°C, 50% inhibition at 2.5 mM at 5°C
50% inhibition at 2.4 mM at 37°C, 50% inhibition at 1.9 mM at 5°C
50% inhibition at 2.7 mM at 37°C, 50% inhibition at 3.4 mM at 5°C
50% inhibition at 9 mM at 37°C, 50% inhibition at 2.5 mM at 5°C
22% inhibition at 5 mM
-
no inhibition at 0.1 mM
-
competitive
-
Ki: 7.5 mM
-
1 mM, 11.5% inhibition
competitive
citrate accumulation under enzyme inhibition restricts the formation of hydroxyl radical in the Fenton reaction through the binding of iron ions, and it thus protects the enzyme from inactivation
competitive
-
weak
-
1 mM, 78% of initial activity
-
competitive
25 mM, 9% inhibition
10 mM
slight
-
noncompetitive, localization of binding pocket on the enzyme outside the active site
-
10 mM
-
3 mM, more than 50% inhibition
-
9686 enzyme: below 3 mM no effect, inhibition above. Wayne enzyme: slight stimulation up to 5 mM, strong inhibition above
-
above 4.0 mM
-
citrate inhibits the enzyme activity by more than 50% at concentrations of 3 mM
-
stimulates at 2 mM, inhibits at higher concentrations
-
3 mM, more than 50% inhibition
-
not
-

Metals and Ions (2 results)

COMMENTARY
EC NUMBER
LITERATURE
ENZYME 3D STRUCTURE
bound to the steroid-binding cavity via Tyr55 and His117, involved in the induced fit mechanism
the citrate ion is identified on the basis of its shape and bonding partners and is located in the active site cavity adjacent to the FAD cofactor. Citrate is anionic like the UDP-alpha-D-galactopyranose substrate. The citrate ion forms salt bridges with UGM residues R288 and H290 and numerous ordered water molecules, thereby participating in a hydrogen-bonding network with the active site residues

3D Structure of Enzyme-Ligand-Complex (PDB) (3949 results)

EC NUMBER
ENZYME 3D STRUCTURE