Information on EC 1.1.1.27 - L-lactate dehydrogenase and Organism(s) Homo sapiens

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Homo sapiens


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


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
1.1.1.27
-
RECOMMENDED NAME
GeneOntology No.
L-lactate dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
(S)-lactate + NAD+ = pyruvate + NADH + H+
show the reaction diagram
the enzyme-NADH-pyruvate ternery complex undergoes a rate-limiting conformational change, in which the substrate loop closes to form a desolvated ternary complex in order to bring the catalytic residue Arg109 into the active site, the catalytic residues Arg109, Asp168, and His195 are highly conserved, catalyic mechanism, detailed overview
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Bifidobacterium shunt
-
-
heterolactic fermentation
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pyruvate fermentation to lactate
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superpathway of glucose and xylose degradation
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-
L-lactaldehyde degradation
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lactate fermentation
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Glycolysis / Gluconeogenesis
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Cysteine and methionine metabolism
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Pyruvate metabolism
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Propanoate metabolism
-
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Metabolic pathways
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Biosynthesis of secondary metabolites
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Microbial metabolism in diverse environments
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Biosynthesis of antibiotics
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SYSTEMATIC NAME
IUBMB Comments
(S)-lactate:NAD+ oxidoreductase
Also oxidizes other (S)-2-hydroxymonocarboxylic acids. NADP+ also acts, more slowly, with the animal, but not the bacterial, enzyme.
CAS REGISTRY NUMBER
COMMENTARY hide
9001-60-9
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
-
the enzyme is involved in development of cancer, especially of hypoxic cancer cells, since the cancer cells relay on LDH-A for the energy supply. The glycolytic phenotype is responsible for the tumorigenicity of hypoxic cells
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(S)-lactate + NAD+
pyruvate + NADH + H+
show the reaction diagram
L-lactate + NAD+
pyruvate + NADH
show the reaction diagram
L-lactate + NAD+
pyruvate + NADH + H+
show the reaction diagram
-
-
-
-
r
pyruvate + NADH + H+
(S)-lactate + NAD+
show the reaction diagram
additional information
?
-
-
LDH is essential for continuous glycolysis necessary for accelerated tumor growth and increased LDH activity occurs already in grade 1 EC carcinomas
-
-
-
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
(S)-lactate + NAD+
pyruvate + NADH + H+
show the reaction diagram
L-lactate + NAD+
pyruvate + NADH
show the reaction diagram
-
-
-
-
r
L-lactate + NAD+
pyruvate + NADH + H+
show the reaction diagram
-
-
-
-
r
additional information
?
-
-
LDH is essential for continuous glycolysis necessary for accelerated tumor growth and increased LDH activity occurs already in grade 1 EC carcinomas
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(abieta-8,11,13-trien-18-ylamino)(oxo)acetic acid
-
-
(benzylamino)(oxo)acetic acid
-
-
(heptylamino)(oxo)acetic acid
-
-
(hexylamino)(oxo)acetic acid
-
-
(nonylamino)(oxo)acetic acid
-
-
([2-cyano-4-[2-([5-hydroxy-2-[(4-methoxybenzyl)carbamoyl]-4-oxo-4H-chromen-8-yl]oxy)ethyl]phenyl]amino)(oxo)acetic acid
-
-
([4-[2-([5-hydroxy-2-[(4-methoxybenzyl)carbamoyl]-4-oxo-4H-chromen-8-yl]oxy)ethyl]-2-methoxyphenyl]amino)(oxo)acetic acid
-
-
([4-[2-([5-hydroxy-2-[(4-methoxybenzyl)carbamoyl]-4-oxo-4H-chromen-8-yl]oxy)ethyl]phenyl]amino)(oxo)acetic acid
-
-
1-hydroxy-6-phenyl-4-(trifluoromethyl)-1H-indol-2-carboxylic acid
-
a N-hydroxyindole, NH1-1, and a competitive inhibitor with respect to both NADH and pyruvate
1-[7-[3,4-dihydroxy-2-imino-7-methyl-5-(propan-2-yl)-2H-naphtho[1,8-bc]furan-8-yl]-2,3,8-trihydroxy-6-methyl-4-(propan-2-yl)naphthalen-1-yl]ethanone
-
-
2,3-dihydroxy-4,6,7-trimethylnaphthalene-1-carboxylic acid
-
-
2,3-dihydroxy-4,6-dimethylnaphthalene-1-carboxylic acid
-
-
2,3-dihydroxy-6,7-dimethyl-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
-
2,3-dihydroxy-6,7-dimethyl-4-propylnaphthalene-1-carboxylic acid
-
-
2,3-dihydroxy-6-methyl-4-(propan-2-yl)-7-[4-(trifluoromethyl)benzyl]naphthalene-1-carboxylic acid
-
-
2,3-dihydroxy-6-methyl-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
-
2,3-dihydroxy-6-methyl-4-propylnaphthalene-1-carboxylic acid
-
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2,3-dihydroxy-6-methyl-7-(2-methylbenzyl)-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
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2,3-dihydroxy-6-methyl-7-(3-methylbenzyl)-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
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2,3-dihydroxy-6-methyl-7-(4-methylbenzyl)-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
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2,3-dihydroxy-6-methyl-7-(phenylmethyl)-4-propylnaphthalene-1-carboxylic acid
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FX11, a competitive inhibitor with respect to both NADH and pyruvate
3,5-dihydroxynaphthalene-2-carboxylic acid
-
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3,7-dihydroxynaphthalene-2-carboxylic acid
-
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3-((3-carbamoyl-7-(3,5-dimethylisoxazol-4-yl)-6-methoxyquinolin-4-yl) amino) benzoic acid
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a quinoline-3-sulfonamide, competitive inhibitor with respect to both NADH and pyruvate
3-(3-nitro-4-pyridyl)pyruvate
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3-([3-carbamoyldimethoxypyrimidin-7-(2,4-dimethoxypyrimidin-5-yl)quinolin-4-yl]amino)benzoic acid
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enzyme binding structure, overview
3-hydroxy-2-oxo-1-oxaspiro[4,5]-dec-3-ene
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3-[7-(2,4-dimethoxypyrimidin-5-yl)-3-sulfamoylquinolin-4-yl]aminobenzoic acid
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enzyme binding structure, overview
4,7-dibromo-3-hydroxynaphthalene-2-carboxylic acid
-
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4-(ethylcarbamoyl)benzoic acid
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6,6'-disulfanediyldipyridine-3-carboxylic acid
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7-(4-chlorobenzyl)-2,3-dihydroxy-6-methyl-4-(propan-2-yl)naphthalene-1-carboxylic acid
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7-benzyl-2,3-dihydroxy-4,6-dimethylnaphthalene-1-carboxylic acid
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7-benzyl-2,3-dihydroxy-6-methyl-4-(propan-2-yl)naphthalene-1-carboxylic acid
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7-benzyl-2,3-dihydroxy-6-methyl-4-propylnaphthalene-1-carboxylic acid
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8'-acetyl-1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)-2,2'-binaphthalene-8-carboxylic acid
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8'-acetyl-8-cyano-1',6,6',7,7'-pentahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)-2,2'-binaphthalen-1-yl acetate
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8'-acetyl-8-cyano-1',6,6',7,7'-pentahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)-2,2'-binaphthalen-1-yl butanoate
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8'-acetyl-8-cyano-1',6,6',7,7'-pentahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)-2,2'-binaphthalen-1-yl pentanoate
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8'-acetyl-8-cyano-1',6,6',7,7'-pentahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)-2,2'-binaphthalen-1-yl propanoate
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8-(2-[4-[(carboxycarbonyl)amino]-3-methoxyphenyl]ethoxy)-5-hydroxy-4-oxo-4H-chromene-2-carboxylic acid
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8-(phenylamino)naphthalene-1-sulfonic acid
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8-([4-[(carboxycarbonyl)amino]-3-methoxybenzyl]oxy)-5-hydroxy-4-oxo-4H-chromene-2-carboxylic acid
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8-[8-acetyl-1,6,7-trihydroxy-3-methyl-5-(propan-2-yl)naphthalen-2-yl]-3,4-dihydroxy-7-methyl-5-(propan-2-yl)-2H-naphtho[1,8-bc]furan-2-one
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amino(oxo)acetic acid
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AZ-33
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a malonic derivative, a competitive inhibitor with respect to both NADH and pyruvate
bis(acetatato-kO)(biphenyl-2,2'-diyl-k2C2,C2')copper
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bis(acetatato-kO)(biphenyl-2,2'-diyl-k2C2,C2')zinc
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Chinese gall
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ethanol extract of the Chinese gall, commonly named Wu Bei Zi, strongly inhibits the enzyme
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epigallocatechin
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the most potent compound with anti-LDH-5 activity under both normoxia and hypoxia conditions
ethyl 3-(3-cyano-4-pyridyl)pyruvate
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galloflavin
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a blocker of LDH-5-ssDNA interactions, preventing RNA synthesis
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GNE-140
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a piperidine derivative LDH-5 inhibitor
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gossypol
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methyl 1-hydroxy-6-phenyl-4-(trifluoromethyl)-1H-indol-2-carboxylate
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a N-hydroxyindole, NH1-2, and a competitive inhibitor with respect to both NADH and pyruvate
naphthalene-2,6-dicarboxylic acid
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-
naphthalene-2,6-disulfonic acid
-
-
oxamate
oxo(pentadecylamino)acetic acid
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oxo(phenylamino)acetic acid
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oxo[(2-phenylethyl)amino]acetic acid
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oxo[(2-phenylpropyl)amino]acetic acid
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oxo[(3-phenylpropyl)amino]acetic acid
-
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oxo[(4-phenylbutan-2-yl)amino]acetic acid
-
-
oxo[(4-phenylbutyl)amino]acetic acid
-
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oxo[(tetrahydrofuran-2-ylmethyl)amino]acetic acid
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oxo[[1-(5,6,7,8-tetrahydronaphthalen-1-yl)ethyl]amino]acetic acid
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-
pyruvate
-
above 0.3 mM
Spatholobus suberectus extract
-
the extract has a strong inhibitory effect on LDH-5 expression and activity inboth estrogen-dependent and estrogen-independent human breast cancer cells
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[(2-ethylphenyl)(phenyl)amino](oxo)acetic acid
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[(2-methoxyethyl)amino](oxo)acetic acid
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[(3,3-diphenylpropyl)amino](oxo)acetic acid
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[(3-methoxypropyl)amino](oxo)acetic acid
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[(3-methylbutyl)amino](oxo)acetic acid
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[(3-methylphenyl)(phenyl)amino](oxo)acetic acid
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[(4-chlorobenzyl)amino](oxo)acetic acid
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[(4-methylbenzyl)amino](oxo)acetic acid
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[(furan-2-ylmethyl)(methyl)amino](oxo)acetic acid
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[(naphthalen-1-ylmethyl)amino](oxo)acetic acid
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[benzyl(methyl)amino](oxo)acetic acid
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[bis(2-methylpiperidin-1-yl)amino](oxo)acetic acid
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[bis(4-benzylpiperazin-1-yl)amino](oxo)acetic acid
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[bis(4-benzylpiperidin-1-yl)amino](oxo)acetic acid
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[bis(4-phenylpiperazin-1-yl)amino](oxo)acetic acid
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[[2-(4-bromophenyl)ethyl]amino](oxo)acetic acid
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-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
direct phosphorylation of LDHA at Y10 and Y83 strongly enhances LDH-5 tetramer formation and cofactor binding, resulting in significantly increased LDH enzymatic activity
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
10.73 - 21.78
(S)-lactate
0.5 - 0.99
NAD+
0.03 - 0.398
pyruvate
additional information
additional information
LDH has different kinetic characteristics in breast tumors compared to normal breast tissues. Tumor LDH affinity in the pyruvate reduction reaction is the same as for normal LDH but Vmax of cancerous LDH is higher relative to normal LDH. In the lactate oxidation reaction, affinity of tumor LDH for lactate and NAD+ is lower than for normal LDH, also the enzyme efficiency for lactate and NAD+ is higher in normal samples. The activation energy for the pyruvate reduction reaction is higher in cancerous tissues. The enzyme in forward reaction in both tissues displays sigmoidal kinetics with respect to pyruvate and NADH
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
-
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.4
(benzylamino)(oxo)acetic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.0025
1-[7-[3,4-dihydroxy-2-imino-7-methyl-5-(propan-2-yl)-2H-naphtho[1,8-bc]furan-8-yl]-2,3,8-trihydroxy-6-methyl-4-(propan-2-yl)naphthalen-1-yl]ethanone
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.004
2,3-dihydroxy-4,6,7-trimethylnaphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.034
2,3-dihydroxy-4,6-dimethylnaphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.002
2,3-dihydroxy-6,7-dimethyl-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.0001
2,3-dihydroxy-6,7-dimethyl-4-propylnaphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.013
2,3-dihydroxy-6-methyl-4-(propan-2-yl)-7-[4-(trifluoromethyl)benzyl]naphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.003
2,3-dihydroxy-6-methyl-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.001
2,3-dihydroxy-6-methyl-4-propylnaphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.003
2,3-dihydroxy-6-methyl-7-(2-methylbenzyl)-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.0002
2,3-dihydroxy-6-methyl-7-(3-methylbenzyl)-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.00003
2,3-dihydroxy-6-methyl-7-(4-methylbenzyl)-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.00059 - 0.00252
3-[7-(2,4-dimethoxypyrimidin-5-yl)-3-sulfamoylquinolin-4-yl]aminobenzoic acid
0.001
7-(4-chlorobenzyl)-2,3-dihydroxy-6-methyl-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.0005
7-benzyl-2,3-dihydroxy-4,6-dimethylnaphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.0002
7-benzyl-2,3-dihydroxy-6-methyl-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.00005
7-benzyl-2,3-dihydroxy-6-methyl-4-propylnaphthalene-1-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.0013
8'-acetyl-1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)-2,2'-binaphthalene-8-carboxylic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.0008
8'-acetyl-8-cyano-1',6,6',7,7'-pentahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)-2,2'-binaphthalen-1-yl acetate
-
pH not specified in the publication, temperature not specified in the publication
0.0006
8'-acetyl-8-cyano-1',6,6',7,7'-pentahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)-2,2'-binaphthalen-1-yl butanoate
-
pH not specified in the publication, temperature not specified in the publication
0.0003
8'-acetyl-8-cyano-1',6,6',7,7'-pentahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)-2,2'-binaphthalen-1-yl pentanoate
-
pH not specified in the publication, temperature not specified in the publication
0.0011
8'-acetyl-8-cyano-1',6,6',7,7'-pentahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)-2,2'-binaphthalen-1-yl propanoate
-
pH not specified in the publication, temperature not specified in the publication
0.0006
8-[8-acetyl-1,6,7-trihydroxy-3-methyl-5-(propan-2-yl)naphthalen-2-yl]-3,4-dihydroxy-7-methyl-5-(propan-2-yl)-2H-naphtho[1,8-bc]furan-2-one
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.0014 - 0.0042
gossypol
10
oxo(phenylamino)acetic acid
-
above, LDH-A, pH not specified in the publication, temperature not specified in the publication
7
oxo[(2-phenylethyl)amino]acetic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
10
oxo[(2-phenylpropyl)amino]acetic acid
-
above, LDH-A, pH not specified in the publication, temperature not specified in the publication
0.9
oxo[(3-phenylpropyl)amino]acetic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
0.8
oxo[(4-phenylbutan-2-yl)amino]acetic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
2
oxo[(4-phenylbutyl)amino]acetic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
1
[(4-chlorobenzyl)amino](oxo)acetic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
2
[(4-methylbenzyl)amino](oxo)acetic acid
-
LDH-A, pH not specified in the publication, temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
150
3,5-dihydroxynaphthalene-2-carboxylic acid
Homo sapiens;
-
pH not specified in the publication, temperature not specified in the publication
5
3,7-dihydroxynaphthalene-2-carboxylic acid
Homo sapiens;
-
pH not specified in the publication, temperature not specified in the publication
0.00051 - 0.0144
3-([3-carbamoyldimethoxypyrimidin-7-(2,4-dimethoxypyrimidin-5-yl)quinolin-4-yl]amino)benzoic acid
0.000039 - 0.0022
3-[7-(2,4-dimethoxypyrimidin-5-yl)-3-sulfamoylquinolin-4-yl]aminobenzoic acid
5.9
4,7-dibromo-3-hydroxynaphthalene-2-carboxylic acid
Homo sapiens;
-
pH not specified in the publication, temperature not specified in the publication
4.6
6,6'-disulfanediyldipyridine-3-carboxylic acid
Homo sapiens;
-
pH not specified in the publication, temperature not specified in the publication
1.1
8-(phenylamino)naphthalene-1-sulfonic acid
Homo sapiens;
-
pH not specified in the publication, temperature not specified in the publication
1.4
naphthalene-2,6-dicarboxylic acid
Homo sapiens;
-
pH not specified in the publication, temperature not specified in the publication
9.8
naphthalene-2,6-disulfonic acid
Homo sapiens;
-
pH not specified in the publication, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
52
NADH oxidation, pH 8.0, temperature not specified in the publication, healthy breast tissue
458.5
-
-
1747
pyruvate reduction, pH 8.0, temperature not specified in the publication, healthy breast tissue
2788
NADH oxidation, pH 8.0, temperature not specified in the publication, breast cancer tissue
4034
pyruvate reduction, pH 8.0, temperature not specified in the publication, breast cancer tissue
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
assay at
7.4
-
assay at
7.5
-
assay at, pyruvate reduction
8
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
additional information
activation energy is measured at 5-42C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
the level of L-lactate dehydrogenase B are specifically increased in non-small cell lung cancer
Manually annotated by BRENDA team
-
endometrial and ovarian
Manually annotated by BRENDA team
-
lactate dehydrogenase-B is silenced by promoter hypermethylation in human prostate cancer
Manually annotated by BRENDA team
-
in patients with tubercular pyothorax, decrease in heart specific aerobic LDH-1 (6fold), LDH-2 (2fold) and LDH-3 (1.5fold)
Manually annotated by BRENDA team
-
lactate dehydrogenase-B is silenced by promoter hypermethylation in human prostate cancer
Manually annotated by BRENDA team
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significant rise in the level of muscle specific anaerobic LDH-5 and LDH-4 in patients with tubercular pyothorax
Manually annotated by BRENDA team
-
primary non-small cell lung cancer cell line
Manually annotated by BRENDA team
-
brain metastatic subline of NCI-H226. L-lactate dehydrogenase B is significantly up-regulated in the conditional medium of NCI-H226Br cells
Manually annotated by BRENDA team
-
lactate dehydrogenase-B is silenced by promoter hypermethylation in human prostate cancer
Manually annotated by BRENDA team
-
patients with tubercular pyothorax show highest levels in LDH-5 followed by LDH-4, LDH-3, LDH-2 and LDH-1
Manually annotated by BRENDA team
-
lactate dehydrogenase-B is silenced by promoter hypermethylation in human prostate cancer
Manually annotated by BRENDA team
-
patients with tubercular pyothorax show highest levels in LDH-5 followed by LDH-4, LDH-2, LDH-3 and LDH-1. In LDH-5 and LDH-4 nearly 4- and 5folds increase in patients
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
-
the subcellular localization of LDH-5 appears to be dependent on the phosphorylation state of Y238
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35000
-
4 * 35000, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
tetramer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
acylation
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lysine acetylation appears as a specific modification of LDH-5. It is involved in the control of its activity. Acetylation at Y5 decreases the LDHA protein level and inhibits LDH-5 activity. Lysine-5 acetylation reduces and be accompanied with increased LDHA protein levels in both early and late stages of pancreatic cancers. Acetylated LDHA can be recognized by a cytosolic chaperone and it is easily degraded by lysosomal proteolysis
phosphoprotein
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LDH-5 can serve as a substrate of the oncogenic viral Src (v-Src) tyrosine kinase and the oncogenic receptor tyrosine kinase FGFR1. Direct phosphorylation of LDHA at Y10 and Y83 strongly enhances LDH-5 tetramer formation and cofactor binding, resulting in significantly increased LDH enzymatic activity. LDHA tyrosine phosphorylation also decides about the translocation of LDH-5 to the nucleus
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
binary complex of LDH with the cofactor NADH and the LDH/NADH-oxamate ternary complex, molecular dynamics, and simulation model from crystal structure at 2.1 A resolution, Protein DataBank entry 1IOZ, overview
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lactate dehydrogenase A in apo form, in ternary complex with oxalate and kanamycin, and in inhibitor-bound form, hanging drop vapour diffusion method, apo-LDHA crystals are grown by mixing of 0.002 ml of 25 mg/ml enzyme protein with 0.002 ml reservoir solution consisting of 100 mM Bis-Tris propane, pH 7.0, 20% v/v PEG 400, and 100 mM LiCl. LDHA-NADH crystals are grown by first incubating 25 mg/ml enzyme protein with 3 mM NADH for 2 h at 4C and then setting up 0.004 ml drops with a 2:1:1 volume ratio of LDHA-NADH, reservoir solution, containing 18% w/v PEG 3350, and 50 mM HEPES, pH 6.8, and another reagent containing 0.16% w/v L-citrulline, 0.16% w/v L-ornithine hydrochloride, 0.16% w/v urea, 0.16% w/v oxalic acid, 0.16% w/v kanamycin monosulfate, and 0.16% w/v L-arginine in 0.02 M HEPES sodium, pH 6.8, 20C. Apo and NADH-bound LDHA crystals appear after three weeks. LDHA-inhibitor complex crystals are obtained by adding 0.010 ml soaking solution containing 20 mM inhibitor, 100 mM HEPES, pH 7.5, 50 mM LiCl, 100 mM bis-tris propane pH 7.0, 20% v/v DMSO, and 25% PEG 8000, to 0.002 ml hanging drops containing apo LDHA crystals and allowing the crystals to sit at room temperature for 24 h, X-ray diffraction structure determination and analysis at 2.1-3.2 A resolution, molecular replacement method using model structure PDB ID1i10
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55
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stable up to
65
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stable for 10 min, 30% loss of activity after 1 h
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
native enzyme from malignant and healthy breast tissue 14.3fold by anion exchange and affinity chromatography
recombinant C-terminally His6-tagged enzyme from Escherichia coli strain BL21(lambdaDE3) by centrfugation at 40000 g, nickel affinity chromatography, dialysis and ultrafiltration, followed by gel filtration, to over 95% purity
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
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multiple initiation sites required for transcription of the LDHA gene are identified in its promoter region, including a cAMP response element (CRE) and E-box motif. The LDHA gene promoter possesses also two conserved hypoxia response elements (HREs) containing functionally essential binding sites for hypoxia-inducible factor 1 (HIF-1) with the consensus sequence 5?-RCGTG-3?, which may strongly suggest an oxygendependent regulation of LDH-5 activity
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recombinant expression of C-terminally His6-tagged enzyme from pET-29b-LDHA vector in Escherichia coli strain BL21(lambdaDE3)
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
Spatholobus suberectus extract has a strong inhibitory effect on LDH-5 expression and activity inboth estrogen-dependent and estrogen-independent human breast cancer cells. Follicle-stimulating hormone, insulin, insulin-like growth factor 1, epidermal growth factor, and tumor necrosis factor alpha, are factors able to affect LDHA gene transcription through relevant intracellular signal transduction systems, including protein kinase A and C signaling pathways
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
medicine