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Information on EC 1.1.1.39 - malate dehydrogenase (decarboxylating)
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1.1.1.39 malate dehydrogenase (decarboxylating)IUBMB Comments
There are several forms of malate dehydrogenases that differ in their use of substrates and cofactors. This particular form is found only in the plant kingdom. Unlike EC 1.1.1.38, which catalyses a similar reaction, this enzyme can not bind oxaloacetate, and thus does not decarboxylate exogeneously-added oxaloacetate. cf. EC 1.1.1.37, malate dehydrogenase; EC 1.1.1.38, malate dehydrogenase (oxaloacetate-decarboxylating); and EC 1.1.1.83, D-malate dehydrogenase (decarboxylating).
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Word Map
- 1.1.1.39
- nadp
-
nadp+-dependent
- fumarate
- l-malate
- alpha-glycerophosphate
- hydrogenosomes
-
alpha-gpd
-
nad+-malic
-
crassulacean
- synthesis
- medicine
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
AT2g13560, At4g00570, AZC3656 protein, cytosolic malic enzyme, decarboxylating NAD-malic enzyme, dehydrogenase, malate, diphosphate nucleotide dependent malic enzyme, DMA, DME, m-NAD-ME, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AZC3656 protein
dehydrogenase, malate
-
-
-
-
DMA
-
-
-
-
DME
m-NAD-ME
malic enzyme
malic enzyme 2
malic enzyme-NAD
ME
ME-NAD
ME1
ME2
NAD(P)+-malic enzyme
NAD-dependent malic enzyme
NAD-malic enzyme
NAD-ME
NAD-ME1
NAD-ME2
NAD-MEH
NAD-preferring malic enzyme
NAD-specific malic enzyme
-
-
-
-
pyruvic-malic carboxylase
-
-
-
-
malic enzyme
-
-
-
-
malic enzyme
Lacticaseibacillus casei BL23 and ATCC 334
-
-
-
ME
-
-
-
-
NAD-malic enzyme
-
-
-
-
NAD-ME
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(S)-malate + NAD+ = pyruvate + CO2 + NADH
-
-
-
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
slow reaction transient in the form of a lag before reaching a steady-state rate in assay
Crassula argentea
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
rapid equilibrium reaction of the intersecting type
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
sequential mechanism, each of the substrate pairs binds randomly to the enzyme
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
sequential mechanism with each substrate bound randomly
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
active site structure, catalytic residues are Y126, R181, K199, D295, N343, and N479
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
catalytic mechanism, malate is bound deeply in the active site, Mn2+ catalyzes the entire reaction, Lys183 is the general base for oxidation, Tyr112-Lys183 functions as the general acid-base pair to catalyze the tautomerization of the enolpyruvate product from decarboxylation to pyruvate, substrate and cofacor binding modes
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
reaction mechanism of oxidative decarboxylation
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
reaction mechanism, active site structure, enzyme-cofactor interactions, overview
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
acid-base chemical mechanism for Ascaris suum malic enzyme
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
isozyme NAD-ME2 and chimeric mutant NAD-ME1q follow a sequential ordered Bi-Ter mechanism, NAD+ being the leading substrate followed by (S)-malate. Hetereodimer NAD-MEH can bind both substrates randomly. Interaction between NAD-ME1 and -ME2 generates a heteromeric isozyme NAD-MEH with a particular kinetic behaviour
(S)-malate + NAD+ = pyruvate + CO2 + NADH
isozyme NAD-ME2 and chimeric mutant NAD-ME1q follow a sequential ordered Bi-Ter mechanism, NAD+ being the leading substrate followed by (S)-malate. Isozyme NAD-ME1 and hetereodimer NAD-MEH can bind both substrates randomly. However, NAD-ME1 shows a preferred route that involves the addition of NAD+ first. interaction between NAD-ME1 and -ME2 generates a heteromeric isozyme NAD-MEH with a particular kinetic behaviour
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
oxidative decarboxylation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
(S)-malate:NAD+ oxidoreductase (decarboxylating)
There are several forms of malate dehydrogenases that differ in their use of substrates and cofactors. This particular form is found only in the plant kingdom. Unlike EC 1.1.1.38, which catalyses a similar reaction, this enzyme can not bind oxaloacetate, and thus does not decarboxylate exogeneously-added oxaloacetate. cf. EC 1.1.1.37, malate dehydrogenase; EC 1.1.1.38, malate dehydrogenase (oxaloacetate-decarboxylating); and EC 1.1.1.83, D-malate dehydrogenase (decarboxylating).
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CAS REGISTRY NUMBER
COMMENTARY
9028-46-0
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(S)-malate + NAD+
?
-
the enzyme plays a special role in the decarboxylation of C4 acids to pyruvate and CO2, which are used in subsequent photosynthesis. pH, NAD+, and coenzyme A levels in the matrix act together to regulate (S)-malate oxidation
-
-
?
(S)-malate + NAD+
?
-
the enzyme plays a special role in the decarboxylation of C4 acids to pyruvate and CO2, which are used in subsequent photosynthesis. pH, NAD+, and coenzyme A levels in the matrix act together to regulate (S)-malate oxidation
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
the enzyme plays a central role in the metabolite flux through the tricarboxylic acid cycle, overview
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
-
the mitochondrial NAD-malic enzyme catalyzes the oxidative decarboxylation of malate to pyruvate and CO2
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
-
the NAD-malic enzyme catalyzes the oxidative decarboxylation of (S)-malate via oxaloacetate, Arg181 is within hydrogen bonding distance of the 1-carboxylate of malate in the active site of the enzyme and interacts with the carboxamide side chain of the nicotinamide ring of NADH, but not with NAD+
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
-
the decarboxylation reaction is preferred, overview
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
-
enzyme is involved in carbon fixation and metabolism, regulation of the pathways, overview
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
-
mitochondrial isozyme ME2 responds to elevated amino acids and serves to supply sufficient pyruvate for increased Krebs cycle flux when glucose is limiting
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
-
the enzyme plays a role in symbiotic N2 fixation, overview
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH + H+
-
the enzyme acts preferably in the direction of malate decarboxylation, the reverse reaction proceeds with much lower rate
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
NAD-ME1, -ME2 and -MEH catalyse the reverse reaction of pyruvate reductive carboxylation with very low catalytic activity, supporting the notion that these isoforms act only in (S)-malate oxidation in plant mitochondria
-
-
ir
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
NAD-ME1, -ME2 and -MEH catalyse the reverse reaction of pyruvate reductive carboxylation with very low catalytic activity, supporting the notion that these isoforms act only in (S)-malate oxidation in plant mitochondria
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
very low activity in the reverse reaction in vitro
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
Lacticaseibacillus casei BL23 and ATCC 334
-
-
-
-
?
(S)-malate + NADP+
pyruvate + CO2 + NADPH
-
15% of the activity with NAD+
-
?
(S)-malate + NADP+
pyruvate + CO2 + NADPH
Crassula argentea
-
14% of the activity with NAD+
-
?
(S)-malate + NADP+
pyruvate + CO2 + NADPH
-
at 1.5% of the activity with NAD+
-
?
(S)-malate + NADP+
pyruvate + NADPH + H+ + CO2
NADP+ shows 22% of the activity with NAD+
-
-
?
(S)-malate + NADP+
pyruvate + NADPH + H+ + CO2
NADP+ shows 22% of the activity with NAD+
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
-
ionized malic acid is the true substrate
-
?
malate + NAD+
pyruvate + CO2 + NADH
-
no decarboxylation of malate in absence of either Mg2+ or NAD+
-
?
malate + NAD+
pyruvate + CO2 + NADH
Crassula argentea
-
activity of the reverse reaction is 1.5% of that of the forward reaction
-
r
pyruvate + CO2 + NADH
(S)-malate + NAD+
-
the rate of carboxylation of pyruvate to malate is lower than for the decarboxylation reaction
-
-
r
pyruvate + CO2 + NADH
(S)-malate + NAD+
Crassula argentea
-
activity is 1.5% of the decarboxylation of (S)-malate
-
r
pyruvate + CO2 + NADH + H+
(S)-malate + NAD+
-
the enzyme acts preferably in the direction of malate decarboxylation, the reverse reaction proceeds with much lower rate
-
-
r
pyruvate + NAD+ + HCO3-
(S)-malate + NADH
-
method optimization of the reverse reaction of the malic enzyme for HCO3- fixation into pyruvic acid to produce L-malic acid with NADH generation including the activity of glucose-6-phosphate dehydrogenase, EC 1.1.1.49, from Leuconostoc mesenteroides
-
-
?
pyruvate + NAD+ + HCO3-
(S)-malate + NADH
-
method optimization of the reverse reaction of the malic enzyme for HCO3- fixation into pyruvic acid to produce L-malic acid with NADH generation including the activity of glucose-6-phosphate dehydrogenase, EC 1.1.1.49, from Leuconostoc mesenteroides
-
-
?
additional information
?
-
-
NAD-ME1 does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-ME1 does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-ME1 does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
-
NAD-ME2 does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-ME2 does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-ME2 does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
-
NAD-MEH does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-MEH does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-MEH does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-ME1 has a regulatory site for L-malate that can also bind fumarate
-
-
?
additional information
?
-
NAD-ME1 has a regulatory site for L-malate that can also bind fumarate
-
-
?
additional information
?
-
NAD-ME1 has a regulatory site for L-malate that can also bind fumarate. L-Malate binding to this site elicits a sigmoidal and low substrate-affinity response, whereas fumarate binding turns NAD-ME1 into a hyperbolic and high substrate affinity enzyme. This effect is also observed when the allosteric site is either removed or altered. Fumarate is not really an activator, but suppresses the inhibitory effect of L-malate. Residues Arg50, Arg80 and Arg84 show different roles in organic acid binding. These residues form a triad, which is the basis of the homo and heterotrophic effects that characterize NAD-ME1
-
-
?
additional information
?
-
NAD-ME1 has a regulatory site for L-malate that can also bind fumarate. L-Malate binding to this site elicits a sigmoidal and low substrate-affinity response, whereas fumarate binding turns NAD-ME1 into a hyperbolic and high substrate affinity enzyme. This effect is also observed when the allosteric site is either removed or altered. Fumarate is not really an activator, but suppresses the inhibitory effect of L-malate. Residues Arg50, Arg80 and Arg84 show different roles in organic acid binding. These residues form a triad, which is the basis of the homo and heterotrophic effects that characterize NAD-ME1
-
-
?
additional information
?
-
the enzyme is unable to decarboxylate oxaloacetate
-
-
-
additional information
?
-
the enzyme is unable to decarboxylate oxaloacetate
-
-
-
additional information
?
-
-
the Ascaris suum enzyme forms complexes with the structurally similar human enzyme
-
-
?
additional information
?
-
-
enzyme shows a strict requirement for 2S-stereochemistry
-
-
?
additional information
?
-
-
the enzyme is unable to decarboxylate oxaloacetate
-
-
-
additional information
?
-
Mnium undulatum
-
comparison of enzyme activity in different species under different conditions, significant differences in the accumulation of malate between day and night, overview
-
-
?
additional information
?
-
-
comparison of enzyme activity in different species under different conditions, significant differences in the accumulation of malate between day and night, overview
-
-
?
additional information
?
-
-
comparison of enzyme activity in different species under different conditions, significant differences in the accumulation of malate between day and night, overview
-
-
?
additional information
?
-
-
comparison of enzyme activity in different species under different conditions, significant differences in the accumulation of malate between day and night, overview
-
-
?
additional information
?
-
the enzyme shows 1% of the forward reaction activity in the reverse reaction and in decarboxylation oxaloacetate. D-malate and succinate are poor substrates showing 3.9% and 8.2% of the activity with (S)-malate
-
-
?
additional information
?
-
the enzyme shows 1% of the forward reaction activity in the reverse reaction and in decarboxylation oxaloacetate. D-malate and succinate are poor substrates showing 3.9% and 8.2% of the activity with (S)-malate
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(S)-malate + NAD+
?
-
the enzyme plays a special role in the decarboxylation of C4 acids to pyruvate and CO2, which are used in subsequent photosynthesis. pH, NAD+, and coenzyme A levels in the matrix act together to regulate (S)-malate oxidation
-
-
?
(S)-malate + NAD+
?
-
the enzyme plays a special role in the decarboxylation of C4 acids to pyruvate and CO2, which are used in subsequent photosynthesis. pH, NAD+, and coenzyme A levels in the matrix act together to regulate (S)-malate oxidation
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
the enzyme plays a central role in the metabolite flux through the tricarboxylic acid cycle, overview
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
-
enzyme is involved in carbon fixation and metabolism, regulation of the pathways, overview
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
-
mitochondrial isozyme ME2 responds to elevated amino acids and serves to supply sufficient pyruvate for increased Krebs cycle flux when glucose is limiting
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
-
the enzyme plays a role in symbiotic N2 fixation, overview
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH + H+
-
the enzyme acts preferably in the direction of malate decarboxylation, the reverse reaction proceeds with much lower rate
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
NAD-ME1, -ME2 and -MEH catalyse the reverse reaction of pyruvate reductive carboxylation with very low catalytic activity, supporting the notion that these isoforms act only in (S)-malate oxidation in plant mitochondria
-
-
ir
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
NAD-ME1, -ME2 and -MEH catalyse the reverse reaction of pyruvate reductive carboxylation with very low catalytic activity, supporting the notion that these isoforms act only in (S)-malate oxidation in plant mitochondria
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
Lacticaseibacillus casei BL23 and ATCC 334
-
-
-
-
?
(S)-malate + NADP+
pyruvate + NADPH + H+ + CO2
NADP+ shows 22% of the activity with NAD+
-
-
?
(S)-malate + NADP+
pyruvate + NADPH + H+ + CO2
NADP+ shows 22% of the activity with NAD+
-
-
?
pyruvate + CO2 + NADH + H+
(S)-malate + NAD+
-
the enzyme acts preferably in the direction of malate decarboxylation, the reverse reaction proceeds with much lower rate
-
-
r
additional information
?
-
-
the Ascaris suum enzyme forms complexes with the structurally similar human enzyme
-
-
?
additional information
?
-
Mnium undulatum
-
comparison of enzyme activity in different species under different conditions, significant differences in the accumulation of malate between day and night, overview
-
-
?
additional information
?
-
-
comparison of enzyme activity in different species under different conditions, significant differences in the accumulation of malate between day and night, overview
-
-
?
additional information
?
-
-
comparison of enzyme activity in different species under different conditions, significant differences in the accumulation of malate between day and night, overview
-
-
?
additional information
?
-
-
comparison of enzyme activity in different species under different conditions, significant differences in the accumulation of malate between day and night, overview
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
-
His362 is involved in NAD+-specific catalysis of NAD-ME, and residue 314 may interact with the bisphosphate of the NAD+ moiety, structure analysis, overview
additional information
-
Arg181 is within hydrogen bonding distance of the 1-carboxylate of malate in the active site of the enzyme and interacts with the carboxamide side chain of the nicotinamide ring of NADH, but not with NAD+
-
additional information
the enzyme uses both NAD+ and NADP+
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Mg2+
Mn2+
NH4+
Ni2+
-
divalent metal ion required, NADP+-linked activity exhibits a maximum at 5 mM Ni2+
Zn2+
5fold activation at 5 mM, only slight activation at 10 mM
additional information
Mg2+
a divalent metal ion, Mn+2 or Mg+2+, is essential for the enzyme reaction
Mg2+
-
strict requirement for a divalent cation, maximal activation at 2 mM
Mg2+
-
no decarboxylation of malate in absence of either Mg2+ or NAD+. Km: 0.04 mM
Mg2+
-
divalent metal ion required, NAD+-linked activity shows maximal activity at 5 mM Mg2+
Mg2+
-
activation by Mn2+, at 1 mM, is 10% and 20% higher than activation with 1 mM Mg2+ in the presence of NAD+ and NADP+
Mn2+
-
activates the enzyme in mitochondria, kinetics, overview
Mn2+
a divalent metal ion, Mn+2 or Mg+2+, is essential for the enzyme reaction
Mn2+
-
strict requirement for a divalent cation, maximal activation at 5 mM
Mn2+
-
reversible structural interconversion to the Lu3+-binding form, metal binding site structure
Mn2+
-
during the catalytic process of malic enzyme, binding of metal ion induces a conformational change within the enzyme from the open form to an intermediate form, which upon binding of L-malate, transforms further into a catalytically competent closed form
NH4+
-
partially rescues the activity of the R181Q mutant by binding in the pocket vacated by the guanidinium group of R181, 2 mol of ammonia bind per mole of active sites, high-affinity Km is 0.7 mM, low-affinity Km is 420 mM
additional information
malic enzyme activity is markedly enhanced by mono- and divalent cations
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5'-AMP
isozyme NAD-ME2, competitive versus NAD+, mixed inhibition versus (S)-malate
CO2
chimeric mutant NAD-ME1q, mixed inhibition versus NAD+ and (S)-malate; isozyme NAD-ME2 and chimeric mutant NAD-ME1q, mixed inhibition versus NAD+ and (S)-malate
fructose 6-phosphate
competitive versus (S)-malate, 70% inhibition at 2.5 mM
L-aspartate
-
slightly competitive to malate, only slight inhibition below pH 6.0
Lu3+
-
strong inhibition, reversible slow-binding mechanism, reversible structural interconversion to the Mn2+-binding form, metal binding site structure
Mn2+
-
inhibits the reductive carboxylation reaction, inhibitory effect is about 20fold reduced by binding of fumarate and L-malate
Urea
-
denaturation, in 3-5 M urea, the enzyme undergoes a reversible tetramer-dimer-monomer quaternary structural change in an acidic pH environment, which resulted in a molten globule state that is prone to aggregate, Mn2+ protects, overview
acetyl-CoA
enzyme activity is allosterically regulated by acetyl-CoA, almost complete inhibition at 0.05 mM
ATP
-
the enzyme is competitively inhibited by ATP up to 10fold. Addition of 1 mM or 5 mM fumarate reverses ATP-dependent inhibition of the enzyme to 55 or 70% of its maximum activity, respectively
NADH
isozyme NAD-ME2, competitive versus NAD+, mixed inhibition versus (S)-malate. NADH shows competitive and mixed-type inhibition versus NAD+ and (S)-malate with chimeric mutant NAD-ME1q; NADH shows competitive and mixed-type inhibition versus NAD+ and (S)-malate with chimeric mutant NAD-ME1q
oxaloacetate
competitive versus (S)-malate, 20% inhibition at 2.5 mM
phosphoenolpyruvate
Crassula argentea
-
activates at low concentrations, deactivation at high concentrations
pyruvate
isozyme NAD-ME2, uncompetitive versus NAD+, mixed inhibition versus (S)-malate. Pyruvate inhibition is uncompetitive with respect to NAD+ and mixed with respect to (S)-malate for the chimeric mutant NAD-ME1q; pyruvate inhibition is uncompetitive with respect to NAD+ and mixed with respect to (S)-malate for the chimeric mutant NAD-ME1q
Tartrate
substrate analogue, isozyme NAD-ME2, uncompetitive versus NAD+, competitive versus (S)-malate
additional information
product inhibition patterns of isozyme NAD-ME2, overview; product inhibition patterns of isozyme NAD-ME2, overview
-
additional information
product inhibition patterns of isozyme NAD-ME2, overview; product inhibition patterns of isozyme NAD-ME2, overview
-
additional information
-
product inhibition patterns of isozyme NAD-ME2, overview; product inhibition patterns of isozyme NAD-ME2, overview
-
additional information
Mnium undulatum
-
keeping plants in CO2-free air suppresses the activities of NAD-ME
-
additional information
-
keeping plants in CO2-free air suppresses the activities of NAD-ME
-
additional information
-
keeping plants in CO2-free air suppresses the activities of NAD-ME
-
additional information
-
keeping plants in CO2-free air suppresses the activities of NAD-ME
-
additional information
-
water stress reduces the enzyme activity in vivo
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
coenzyme A
-
serves to broaden the pH-optimum, at pH 7.5 approximately 4fold stimulation, the effect is more marked when HCO3 is also present, below pH 7 no effect on activity
coenzyme A
-
serves to broaden the pH-optimum, at pH 7.5 approximately 4fold stimulation, the effect is more marked when HCO3 is also present, below pH 7 no effect on activity
fumarate
Arabidopsis NAD-ME1 is strongly stimulated by fumarate. Fumarate binding turns NAD-ME1 into a hyperbolic and high substrate affinity enzyme. This effect is also observed when the allosteric site is either removed or altered. Hence, fumarate is not really an activator, but suppresses the inhibitory effect of L-malate. Binding of L-malate and fumarate at the same allosteric site
fumarate
Arabidopsis NAD-ME1 is strongly stimulated by fumarate. Fumarate binding turns NAD-ME1 into a hyperbolic and high substrate affinity enzyme. This effect is also observed when the allosteric site is either removed or altered. Hence, fumarate is not really an activator, but suppresses the inhibitory effect of L-malate. Binding of L-malate and fumarate at the same allosteric site. Arg84 is essential for fumarate activation
fumarate
-
activates in both reaction directions synergistically with L-malate both binding at separate allosteric sites different from the active site, R105 and K143 are involved
L-malate
-
activates in both reaction directions synergistically with fumarate both binding at separate allosteric sites different from the active site, R105 and K143 are involved
phosphoenolpyruvate
Crassula argentea
-
activates at low concentrations, decativation at high concentrations
additional information
-
no activation by CoA and acetyl-CoA, poor activation by ATP and AMP
-
additional information
no activation by CoA and acetyl-CoA, poor activation by ATP and AMP
-
additional information
no activation by CoA and acetyl-CoA, poor activation by ATP and AMP
-
additional information
-
no activation by oxaloacetate, poor activation by ATP and AMP
-
additional information
no activation by oxaloacetate, poor activation by ATP and AMP
-
additional information
no activation by oxaloacetate, poor activation by ATP and AMP
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Breast Neoplasms
Kinetic mechanism of the cytosolic malic enzyme from human breast cancer cell line.
Breast Neoplasms
Mitochondrial malic enzyme 2 promotes breast cancer metastasis via stabilizing HIF-1? under hypoxia.
Carcinoma
Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma.
Carcinoma, Hepatocellular
Activities of enzymes of lipid metabolism in Morris hepatoma 7800 C1 cells.
Carcinoma, Hepatocellular
Purification, kinetic behavior, and regulation of NAD(P)+ malic enzyme of tumor mitochondria.
Corneal Dystrophies, Hereditary
Linkage analysis in granular corneal dystrophy (Groenouw I), Schnyder's crystalline corneal dystrophy, and Reis-BĆĀĆĀ¼cklers' corneal dystrophy.
Friedreich Ataxia
Friedreich's ataxia: malic enzyme activity in cellular fractions of cultured skin fibroblasts.
Friedreich Ataxia
Friedreich's disease: IV. Reduced mitochondrial malic enzyme activity in heterozygotes.
Friedreich Ataxia
Mitochondrial malic enzyme in Friedreich's ataxia: failure to demonstrate reduced activity in cultured fibroblasts.
Friedreich Ataxia
Normal fibroblast mitochondrial malic enzyme activity in Friedreich's ataxia.
Friedreich Ataxia
Normal mitochondrial malic enzyme levels in Friedreich's ataxia fibroblasts.
glucose-6-phosphatase deficiency
Analysis of the albino-locus region of the mouse: IV. Characterization of 34 deficiencies.
Glycogen Storage Disease Type I
Analysis of the albino-locus region of the mouse: IV. Characterization of 34 deficiencies.
Insulinoma
Mitochondrial malic enzyme (ME2) in pancreatic islets of the human, rat and mouse and clonal insulinoma cells.
Leukemia
Enzyme activities of NADPH-forming metabolic pathways in normal and leukemic leukocytes.
Leukemia, Myeloid, Acute
Enzyme activities of NADPH-forming metabolic pathways in normal and leukemic leukocytes.
Malaria
Mitochondrial NAD+-dependent malic enzyme from Anopheles stephensi: a possible novel target for malaria mosquito control.
malate dehydrogenase (decarboxylating) deficiency
Friedreich ataxia: III. Mitochondrial malic enzyme deficiency.
malate dehydrogenase (decarboxylating) deficiency
Friedreich's ataxia: malic enzyme activity in cellular fractions of cultured skin fibroblasts.
malate dehydrogenase (decarboxylating) deficiency
Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer.
malate dehydrogenase (oxaloacetate-decarboxylating) deficiency
Friedreich ataxia: III. Mitochondrial malic enzyme deficiency.
Neoplasm Metastasis
Mitochondrial malic enzyme 2 promotes breast cancer metastasis via stabilizing HIF-1? under hypoxia.
Neoplasms
Kinetic mechanism of the cytosolic malic enzyme from human breast cancer cell line.
Neoplasms
Malic enzyme and malate dehydrogenase activities in rat tracheal epithelial cells during the progression of neoplasia.
Neoplasms
Nuclear thyroid hormone receptors, alpha-glycerophosphate dehydrogenases, and malic enzyme in N-nitrosomethylurea-induced rat mammary tumors.
Neoplasms
Purification and characterization of the cytosolic NADP(+)-dependent malic enzyme from human breast cancer cell line.
Neoplasms
Purification of tumor mitochondrial malic enzyme by specific ligand affinity chromatography.
Neoplasms
The pathways of glutamate and glutamine oxidation by tumor cell mitochondria. Role of mitochondrial NAD(P)+-dependent malic enzyme.
Squamous Cell Carcinoma of Head and Neck
Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.59
(S)-malate
pH 7.8, 30ĆĀ°C, AZC3656, in presence of 1 mM fumarate
0.64
(S)-malate
pH 7.8, 30ĆĀ°C, AZC3656, in presence of 10 mM succinate
2 - 3
(S)-malate
-
pH 8.5, 25ĆĀ°C, recombinant mutant R181Q in presence of 60 mM guanidinium
2.6
(S)-malate
isozyme NAD-ME2, pH 6.5, temperature not specified in the publication
2.7
(S)-malate
pH 6.5, temperature not specified in the publication, NAD-MEH
3
(S)-malate
pH 6.4, temperature not specified in the publication, NAD-ME1
3
(S)-malate
pH 6.6, temperature not specified in the publication, NAD-ME2
8
(S)-malate
-
pH 8.5, 25ĆĀ°C, recombinant mutant R181Q, in presence of 60 mM NH4+
27.6
(S)-malate
pH 7.8, 30ĆĀ°C, AZC3656, in presence of 0.05 mM acetyl-CoA
0.5
NAD+
pH 6.4, temperature not specified in the publication, NAD-ME1
0.5
NAD+
pH 6.6, temperature not specified in the publication, NAD-ME2
0.55
NAD+
pH 6.5, temperature not specified in the publication, NAD-MEH
1.1
NAD+
isozyme NAD-ME2, pH 6.5, temperature not specified in the publication
additional information
additional information
-
detailed kinetic mechanism study, steady-state kinetics
-
additional information
additional information
-
Michaelis-Menten kinetics
-
additional information
additional information
steady-state kinetics, overview
-
additional information
additional information
-
kinetics of wild-type and mutant enzymes, primary deuterium and 13C isotope effects of mutant R181Q in the absence and presence of ammonium ions, overview
-
additional information
additional information
-
primary deuterium and 13C kinetic isotope effects, kinetics, and kinetic mechanism of wild-type and mutant enzymes, overview
-
additional information
additional information
-
kinetic analysis and comparison of the different isozymes MAD-ME1, NAD-ME2, and NAD-MEH, and of mutants NADME1q and NAD-ME2q, overview
-
additional information
additional information
kinetic analysis and comparison of the different isozymes MAD-ME1, NAD-ME2, and NAD-MEH, and of mutants NADME1q and NAD-ME2q, overview
-
additional information
additional information
kinetic analysis and comparison of the different isozymes MAD-ME1, NAD-ME2, and NAD-MEH, and of mutants NADME1q and NAD-ME2q, overview
-
additional information
additional information
kinetic mechanisms of homodimers NAD-ME1 and NAD-ME2, and of NAD-ME heterodimer NAD-MEH, overview. The first 176 amino acids are associated with the differences observed in the kinetic mechanisms of the enzymes. Activity of NAD-ME1 in the direction of malate decarboxylation shows a hyperbolic response, proposed kinetic model for NAD-ME1. Isozyme NAD-ME2 follows a sequential ordered Bi-Ter mechanism. Kinetic properties and mechanism of chimeric mutant NAD-ME1q, overview
-
additional information
additional information
kinetic mechanisms of homodimers NAD-ME1 and NAD-ME2, and of NAD-ME heterodimer NAD-MEH, overview. The first 176 amino acids are associated with the differences observed in the kinetic mechanisms of the enzymes. Activity of NAD-ME1 in the direction of malate decarboxylation shows a hyperbolic response, proposed kinetic model for NAD-ME1. Isozyme NAD-ME2 follows a sequential ordered Bi-Ter mechanism. Kinetic properties and mechanism of chimeric mutant NAD-ME1q, overview
-
additional information
additional information
-
kinetic mechanisms of homodimers NAD-ME1 and NAD-ME2, and of NAD-ME heterodimer NAD-MEH, overview. The first 176 amino acids are associated with the differences observed in the kinetic mechanisms of the enzymes. Activity of NAD-ME1 in the direction of malate decarboxylation shows a hyperbolic response, proposed kinetic model for NAD-ME1. Isozyme NAD-ME2 follows a sequential ordered Bi-Ter mechanism. Kinetic properties and mechanism of chimeric mutant NAD-ME1q, overview
-
additional information
additional information
kinetic mechanisms of homodimers NAD-ME1 and NAD-ME2, and of NAD-ME heterodimer NAD-MEH, overview. The first 176 amino acids are associated with the differences observed in the kinetic mechanisms of the enzymes. Activity of NAD-ME1 in the direction of malate decarboxylation shows a hyperbolic response, proposed kinetic model for NAD-ME1. Kinetic properties and mechanism of chimeric mutant NAD-ME1q, overview
-
additional information
additional information
kinetic mechanisms of homodimers NAD-ME1 and NAD-ME2, and of NAD-ME heterodimer NAD-MEH, overview. The first 176 amino acids are associated with the differences observed in the kinetic mechanisms of the enzymes. Activity of NAD-ME1 in the direction of malate decarboxylation shows a hyperbolic response, proposed kinetic model for NAD-ME1. Kinetic properties and mechanism of chimeric mutant NAD-ME1q, overview
-
additional information
additional information
-
kinetic mechanisms of homodimers NAD-ME1 and NAD-ME2, and of NAD-ME heterodimer NAD-MEH, overview. The first 176 amino acids are associated with the differences observed in the kinetic mechanisms of the enzymes. Activity of NAD-ME1 in the direction of malate decarboxylation shows a hyperbolic response, proposed kinetic model for NAD-ME1. Kinetic properties and mechanism of chimeric mutant NAD-ME1q, overview
-
additional information
additional information
-
kinetics analysis of isozymes ME2 and ME3
-
additional information
additional information
Arabidopsis NAD-ME1 exhibits a non-hyperbolic behavior for the substrate L-malate and presents a sigmoidal kinetic response for L-malate. Fumarate binding turns NAD-ME1 into a hyperbolic and high substrate affinity enzyme, overview
-
additional information
additional information
Arabidopsis NAD-ME1 exhibits a non-hyperbolic behavior for the substrate L-malate and presents a sigmoidal kinetic response for L-malate. Fumarate binding turns NAD-ME1 into a hyperbolic and high substrate affinity enzyme, overview
-
additional information
additional information
NAD-ME2 shows a typical hyperbolic behavior
-
additional information
additional information
NAD-ME2 shows a typical hyperbolic behavior
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
31.1
(S)-malate
pH 6.4, temperature not specified in the publication, NAD-ME1
39
(S)-malate
pH 6.5, temperature not specified in the publication, NAD-MEH
44.1
(S)-malate
pH 6.6, temperature not specified in the publication, NAD-ME2
46
(S)-malate
isozyme NAD-ME2, pH 6.5, temperature not specified in the publication
31.1
NAD+
pH 6.4, temperature not specified in the publication, NAD-ME1
39
NAD+
pH 6.5, temperature not specified in the publication, NAD-MEH
44.1
NAD+
pH 6.6, temperature not specified in the publication, NAD-ME2
46
NAD+
isozyme NAD-ME2, pH 6.5, temperature not specified in the publication
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
10.3
(S)-malate
pH 6.4, temperature not specified in the publication, NAD-ME1
14.2
(S)-malate
pH 6.5, temperature not specified in the publication, NAD-MEH
14.7
(S)-malate
pH 6.6, temperature not specified in the publication, NAD-ME2
60.2
NAD+
pH 6.4, temperature not specified in the publication, NAD-ME1
67
NAD+
pH 6.5, temperature not specified in the publication, NAD-MEH
88.2
NAD+
pH 6.6, temperature not specified in the publication, NAD-ME2
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
7.4
fructose 6-phosphate
pH 7.2, 30ĆĀ°C, versus (S)-malate
0.45
5'-AMP
versus NAD+, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
1.5
5'-AMP
versus (S)-malate, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
3
CO2
versus NAD+, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
7
CO2
versus (S)-malate, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
0.041
NADH
versus (S)-malate, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
0.15
NADH
versus NAD+, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
11
pyruvate
versus NAD+, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
14
pyruvate
versus (S)-malate, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
0.8
Tartrate
versus (S)-malate, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
4
Tartrate
versus NAD+, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
additional information
additional information
-
inhibition patterns by measuring the initial rate as a function of malate or NAD+ with NAD+ or malate maintained equal to its Km at different fixed concentrations of oxalate, including zero, Ki, 2Ki, and 4Ki at pH 7.0 and 30 mM free Mg2+
-
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.201
NAD+-dependent ME activity in the wild-type strain, pH 7.8, 30ĆĀ°C, AZC3656
36.09
4.25
additional information
additional information
-
design of an assay procedure to minimize the influence of (S)-malate dehydrogenase and other factors
additional information
Mnium undulatum
-
changes in NADH contents in the leaves of plant species towards the end of the light or darkness periods, diurnal changes in malate and citrate contents in gametophores kept under control, hypoxia, high irradiance, drought stress, and CO2-free air conditions, comparison to other species, overiew
additional information
-
changes in NADH contents in the leaves of plant species towards the end of the light or darkness periods, diurnal changes in malate and citrate contents in gametophores kept under control, hypoxia, high irradiance, drought stress, and CO2-free air conditions, comparison to other species, overiew
additional information
-
changes in NADH contents in the leaves of plant species towards the end of the light or darkness periods, diurnal changes in malate and citrate contents in gametophores kept under control, hypoxia, high irradiance, drought stress, and CO2-free air conditions, comparison to other species, overiew
additional information
-
changes in NADH contents in the leaves of plant species towards the end of the light or darkness periods, diurnal changes in malate and citrate contents in gametophores kept under control, hypoxia, high irradiance, drought stress, and CO2-free air conditions, comparison to other species, overiew
additional information
-
isozyme expression levels, pyruvate cycling and isozyme activity in pancreatic islets, overview
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.4
6.5
6.6
6.7
6.8
6.9
7.3
7.4
7.5
7.8
AZC3656 shows high NAD+-ME activity at pH 7.8, with Michaelis-Menten-like kinetics, at various concentrations of malate, The enzyme exhibits only a very limited positive cooperativity with respect to malate
8.3
7
-
catalytically competent enzyme-substrate complex formed upon binding malate
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.8 - 7.6
-
pH 5.8: about 60% of maximal activity, pH 7.6: about 40% of maximal activity
7 - 8.7
-
pH 7.0: about 30% of maximal activity, pH 8.7: about 45% of maximal activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
30
37
50
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30 - 60
-
30ĆĀ°C: about 35% of maximal activity, 60ĆĀ°C: about 50% of maximal activity
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
isozyme NAD-ME1; isozyme NAD-ME1 encoded by gene AtNAD-ME1
UniProt
brenda
isozyme NAD-ME2; isozyme NAD-ME2 encoded by gene AtNAD-ME2
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
the level of the enzyme in wild-type bacteroids is not limiting for N2-fixation
brenda
-
in mesophyll cells, 100% activity is found in cytosol fractions
brenda
additional information
NAD-ME1and -2 subunits show a distinct patterns of accumulation in the separate components of the floral organ
brenda
leaf crude extracts contain about 20% higher NAD-ME specific activities at the end of the night period than at the end of the day period, isozyme NAD-ME1 is more abundant during the night period
brenda
leaf crude extracts contain about 20% higher NAD-ME specific activities at the end of the night period than at the end of the day period, isozyme NAD-ME2 is more abundant during the night period
brenda
NAD-MEH and NADME1 act in concert in this tissue
brenda
the NAD-ME1 subunit is present at a slightly higher proportion than the NAD-ME2 subunit, and thus, NAD-MEH and NADME1 act in concert in this tissue
brenda
-
two molecular forms of malic enzyme are present in herring spermatozoa: an NAD-preferring malic enzyme with very high activity and an NADP-specific malic enzyme (EC 1.1.1.40) with much lower activity (ratio about 33:1)
brenda
-
two molecular forms of malic enzyme are present in herring spermatozoa: an NAD-preferring malic enzyme with very high activity and an NADP-specific malic enzyme (EC 1.1.1.40) with much lower activity (ratio about 33:1)
brenda
-
two molecular forms of malic enzyme are present in herring spermatozoa: an NAD-preferring malic enzyme with very high activity and an NADP-specific malic enzyme (EC 1.1.1.40) with much lower activity (ratio about 33:1)
brenda
-
two molecular forms of malic enzyme are present in herring spermatozoa: an NAD-preferring malic enzyme with very high activity and an NADP-specific malic enzyme (EC 1.1.1.40) with much lower activity (ratio about 33:1)
brenda
-
two molecular forms of malic enzyme are present in herring spermatozoa: an NAD-preferring malic enzyme with very high activity and an NADP-specific malic enzyme (EC 1.1.1.40) with much lower activity (ratio about 33:1)
brenda
additional information
-
no enzyme activity is observed experimentally in chloroplasts of mesophyll and bundle sheath cells
brenda
additional information
tissue specific expression of the isozyme, overview
brenda
additional information
tissue specific expression of the isozyme, overview
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information