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Information on EC 1.1.1.27 - L-lactate dehydrogenase and Organism(s) Homo sapiens and UniProt Accession P07864

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EC Tree
IUBMB Comments
Also oxidizes other (S)-2-hydroxymonocarboxylic acids. NADP+ also acts, more slowly, with the animal, but not the bacterial, enzyme.
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Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
UNIPROT: P07864
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
Synonyms
lactate dehydrogenase, lactic dehydrogenase, ldh-a, lactate dehydrogenase a, l-lactate dehydrogenase, ldh-5, lactic acid dehydrogenase, ldh-1, pfldh, alpha-hydroxybutyrate dehydrogenase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
alpha-HBDH
-
-
alpha-hydroxybutyrate dehydrogenase
-
-
dehydrogenase, lactate
-
-
-
-
Epsilon crystallin
-
-
-
-
epsilon-crystallin
-
-
-
-
HBDH
-
-
Immunogenic protein p36
-
-
-
-
L(+)-nLDH
-
-
-
-
L-(+)-lactate dehydrogenase
-
-
-
-
L-lactate dehydrogenase B
-
-
L-lactic acid dehydrogenase
-
-
-
-
L-lactic dehydrogenase
-
-
-
-
L-LDH
-
-
-
-
lactate dehydrogenase
lactate dehydrogenase 5
-
lactate dehydrogenase A
-
lactate dehydrogenase B
-
lactate dehydrogenase NAD-dependent
-
-
-
-
lactic acid dehydrogenase
-
-
-
-
lactic dehydrogenase
-
-
-
-
LDH-1
-
-
LDH-2
-
-
LDH-3
-
-
LDH-4
-
-
LDH-5
LDH-A
-
-
LDH1
-
-
NAD-lactate dehydrogenase
-
-
-
-
proteins, specific or class, anoxic stress response, p34
-
-
-
-
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
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
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
-
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
-
-
-
r
pyruvate + NADH + H+
(S)-lactate + NAD+
show the reaction diagram
-
-
-
r
(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 SUBSTRATE
NATURAL 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
-
-
-
r
(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
INHIBITOR
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
-
-
2,3-dihydroxy-6-methyl-7-(2-methylbenzyl)-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
-
2,3-dihydroxy-6-methyl-7-(3-methylbenzyl)-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
-
2,3-dihydroxy-6-methyl-7-(4-methylbenzyl)-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
-
3,5-dihydroxynaphthalene-2-carboxylic acid
-
-
3,7-dihydroxynaphthalene-2-carboxylic acid
-
-
3-((3-carbamoyl-7-(3,5-dimethylisoxazol-4-yl)-6-methoxyquinolin-4-yl) amino) benzoic acid
a quinoline-3-sulfonamide, competitive inhibitor with respect to both NADH and pyruvate
3-(3-nitro-4-pyridyl)pyruvate
-
-
3-([3-carbamoyldimethoxypyrimidin-7-(2,4-dimethoxypyrimidin-5-yl)quinolin-4-yl]amino)benzoic acid
enzyme binding structure, overview
3-hydroxy-2-oxo-1-oxaspiro[4,5]-dec-3-ene
-
-
3-[7-(2,4-dimethoxypyrimidin-5-yl)-3-sulfamoylquinolin-4-yl]aminobenzoic acid
enzyme binding structure, overview
4,7-dibromo-3-hydroxynaphthalene-2-carboxylic acid
-
-
4-(ethylcarbamoyl)benzoic acid
-
-
6,6'-disulfanediyldipyridine-3-carboxylic acid
-
-
6-benzyl-3,4-dihydroxy-7-methyl-1-propylnaphthalene-2-carboxylic acid
FX11, a competitive inhibitor with respect to both NADH and pyruvate
7-(4-chlorobenzyl)-2,3-dihydroxy-6-methyl-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
-
7-benzyl-2,3-dihydroxy-4,6-dimethylnaphthalene-1-carboxylic acid
-
-
7-benzyl-2,3-dihydroxy-6-methyl-4-(propan-2-yl)naphthalene-1-carboxylic acid
-
-
7-benzyl-2,3-dihydroxy-6-methyl-4-propylnaphthalene-1-carboxylic acid
-
-
8'-acetyl-1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)-2,2'-binaphthalene-8-carboxylic acid
-
-
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
-
-
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
-
-
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
-
-
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
-
-
8-(2-[4-[(carboxycarbonyl)amino]-3-methoxyphenyl]ethoxy)-5-hydroxy-4-oxo-4H-chromene-2-carboxylic acid
-
-
8-(phenylamino)naphthalene-1-sulfonic acid
-
-
8-([4-[(carboxycarbonyl)amino]-3-methoxybenzyl]oxy)-5-hydroxy-4-oxo-4H-chromene-2-carboxylic acid
-
-
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
-
-
amino(oxo)acetic acid
-
-
AZ-33
a malonic derivative, a competitive inhibitor with respect to both NADH and pyruvate
bis(acetatato-kO)(biphenyl-2,2'-diyl-k2C2,C2')copper
-
-
bis(acetatato-kO)(biphenyl-2,2'-diyl-k2C2,C2')zinc
-
-
Chinese gall
ethanol extract of the Chinese gall, commonly named Wu Bei Zi, strongly inhibits the enzyme
-
epigallocatechin
the most potent compound with anti-LDH-5 activity under both normoxia and hypoxia conditions
ethyl 3-(3-cyano-4-pyridyl)pyruvate
-
-
galloflavin
a blocker of LDH-5-ssDNA interactions, preventing RNA synthesis
GNE-140
a piperidine derivative LDH-5 inhibitor
gossypol
-
-
methyl 1-hydroxy-6-phenyl-4-(trifluoromethyl)-1H-indol-2-carboxylate
a N-hydroxyindole, NH1-2, and a competitive inhibitor with respect to both NADH and pyruvate
naphthalene-2,6-dicarboxylic acid
-
-
naphthalene-2,6-disulfonic acid
-
-
oxamate
oxo(pentadecylamino)acetic acid
-
-
oxo(phenylamino)acetic acid
-
-
oxo[(2-phenylethyl)amino]acetic acid
-
-
oxo[(2-phenylpropyl)amino]acetic acid
-
-
oxo[(3-phenylpropyl)amino]acetic acid
-
-
oxo[(4-phenylbutan-2-yl)amino]acetic acid
-
-
oxo[(4-phenylbutyl)amino]acetic acid
-
-
oxo[(tetrahydrofuran-2-ylmethyl)amino]acetic acid
-
-
oxo[[1-(5,6,7,8-tetrahydronaphthalen-1-yl)ethyl]amino]acetic acid
-
-
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
-
[(2-ethylphenyl)(phenyl)amino](oxo)acetic acid
-
-
[(2-methoxyethyl)amino](oxo)acetic acid
-
-
[(3,3-diphenylpropyl)amino](oxo)acetic acid
-
-
[(3-methoxypropyl)amino](oxo)acetic acid
-
-
[(3-methylbutyl)amino](oxo)acetic acid
-
-
[(3-methylphenyl)(phenyl)amino](oxo)acetic acid
-
-
[(4-chlorobenzyl)amino](oxo)acetic acid
-
-
[(4-methylbenzyl)amino](oxo)acetic acid
-
-
[(furan-2-ylmethyl)(methyl)amino](oxo)acetic acid
-
-
[(naphthalen-1-ylmethyl)amino](oxo)acetic acid
-
-
[benzyl(methyl)amino](oxo)acetic acid
-
-
[bis(2-methylpiperidin-1-yl)amino](oxo)acetic acid
-
-
[bis(4-benzylpiperazin-1-yl)amino](oxo)acetic acid
-
-
[bis(4-benzylpiperidin-1-yl)amino](oxo)acetic acid
-
-
[bis(4-phenylpiperazin-1-yl)amino](oxo)acetic acid
-
-
[[2-(4-bromophenyl)ethyl]amino](oxo)acetic acid
-
-
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
-
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
-
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
0.6
lactate oxidation, pH 8.0, 25°C, healthy breast tissue
0.63
lactate oxidation, pH 8.0, 25°C, breast cancer tissue
1.237
NAD+ reduction, pH 8.0, 25°C, healthy breast tissue
1.282
NAD+ reduction, pH 8.0, 25°C, breast cancer tissue
1.37
NADH oxidation, pH 8.0, 25°C, healthy breast tissue
1.747
pyruvate reduction, pH 8.0, 25°C, healthy breast tissue
2.788
NADH oxidation, pH 8.0, 25°C, breast cancer tissue
4.034
pyruvate reduction, pH 8.0, 25°C, breast cancer tissue
458.5
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
assay at
7.4
-
assay at
7.5
assay at, pyruvate reduction
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
additional information
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
normal and malignant human breast tissues
Manually annotated by BRENDA team
normal and malignant human breast tissues. The enzyme is highly expressed in breast
Manually annotated by BRENDA team
-
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
-
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
lactate dehydrogenase (LDH) is a critical enzyme during aerobic glycolysis as it is typically responsible for the production of lactate and regeneration of NAD+, which allows for the continued functioning of glycolysis even in the absence of oxygen. LDH is the final enzyme in glycolysis pathway that catalyzes interconversion of pyruvate and lactate and it also regenerates NAD+, which is necessary for continued high glycolysis rate in cancer cells
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
LDHC_HUMAN
332
0
36311
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35000
-
4 * 35000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
tetramer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
acylation
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
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
-
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 4°C 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, 20°C. 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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55
-
stable up to
65
-
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
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
-
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
recombinant expression of C-terminally His6-tagged enzyme from pET-29b-LDHA vector in Escherichia coli strain BL21(lambdaDE3)
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
low LDH affinity kinetics can be a diagnostic parameter for human breast cancer
diagnostics
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Pettit, S.M.; Nealon, D.A.; Henderson, A.R.
Purification of lactate dehydrogenase isoenzyme-5 from human liver
Clin. Chem.
27
88-93
1981
Homo sapiens
Manually annotated by BRENDA team
LeVan, K.M.; Goldberg, E.
Properties of human testis-specific lactate dehydrogenase expressed from Escherichia coli
Biochem. J.
273
587-592
1991
Homo sapiens
Manually annotated by BRENDA team
Chen, Y.; Zhang, H.; Xu, A.; Li, N.; Liu, J.; Liu, C.; Lv, D.; Wu, S.; Huang, L.; Yang, S.; He, D.; Xiao, X.
Elevation of serum L-lactate dehydrogenase B correlated with the clinical stage of lung cancer
Lung Cancer
54
95-102
2006
Homo sapiens
Manually annotated by BRENDA team
Leiblich, A.; Cross, S.S.; Catto, J.W.; Phillips, J.T.; Leung, H.Y.; Hamdy, F.C.; Rehman, I.
Lactate dehydrogenase-B is silenced by promoter hypermethylation in human prostate cancer
Oncogene
25
2953-2960
2006
Homo sapiens (P07195)
Manually annotated by BRENDA team
Simaga, S.; Abramic, M.; Osmak, M.; Babic, D.; Ilic-Forko, J.
Total tissue lactate dehydrogenase activity in endometrial carcinoma
Int. J. Gynecol. Cancer
18
1272-1278
2008
Homo sapiens
Manually annotated by BRENDA team
Pineda, J.R.; Callender, R.; Schwartz, S.D.
Ligand binding and protein dynamics in lactate dehydrogenase
Biophys. J.
93
1474-1483
2007
Homo sapiens
Manually annotated by BRENDA team
Lemire, J.; Mailloux, R.J.; Appanna, V.D.
Mitochondrial lactate dehydrogenase is involved in oxidative-energy metabolism in human astrocytoma cells (CCF-STTG1)
PLoS ONE
3
e1550
2008
Homo sapiens
Manually annotated by BRENDA team
Ahmad, R.; Alam, M.; Siddiqui, M.; Hasnain, A.
Adjustments of serum lactate dehydrogenase isoenzymes and their significance in monitoring the treatment in patients with tubercular pyothorax
Indian J. Clin. Biochem.
23
181-185
2008
Homo sapiens
Manually annotated by BRENDA team
Granchi, C.; Bertini, S.; Macchia, M.; Minutolo, F.
Inhibitors of lactate dehydrogenase isoforms and their therapeutic potentials
Curr. Med. Chem.
17
672-697
2010
Bos taurus, Homo sapiens, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale
Manually annotated by BRENDA team
Kolappan, S.; Shen, D.L.; Mosi, R.; Sun, J.; McEachern, E.J.; Vocadlo, D.J.; Craig, L.
Structures of lactate dehydrogenase A (LDHA) in apo, ternary and inhibitor-bound forms
Acta Crystallogr. Sect. D
71
185-195
2015
Homo sapiens (P00338), Homo sapiens
Manually annotated by BRENDA team
Talaiezadeh, A.; Shahriari, A.; Tabandeh, M.R.; Fathizadeh, P.; Mansouri, S.
Kinetic characterization of lactate dehydrogenase in normal and malignant human breast tissues
Cancer Cell Int.
15
19
2015
Homo sapiens (P07864), Homo sapiens
Manually annotated by BRENDA team
Brisson, L.; Banski, P.; Sboarina, M.; Dethier, C.; Danhier, P.; Fontenille, M.J.; Van Hee, V.F.; Vazeille, T.; Tardy, M.; Falces, J.; Bouzin, C.; Porporato, P.E.; Frederick, R.; Michiels, C.; Copetti, T.; Sonveaux, P.
Lactate dehydrogenase B controls lysosome activity and autophagy in cancer
Cancer Cell
30
418-431
2016
Homo sapiens (P07195)
Manually annotated by BRENDA team
Augoff, K.; Hryniewicz-Jankowska, A.; Tabola, R.
Lactate dehydrogenase 5: an old friend and a new hope in the war on cancer
Cancer Lett.
358
1-7
2015
Homo sapiens (P00338)
Manually annotated by BRENDA team
Pizzuto, R.; Paventi, G.; Porcile, C.; Sarnataro, D.; Daniele, A.; Passarella, S.
L-Lactate metabolism in HEP G2 cell mitochondria due to the L-lactate dehydrogenase determines the occurrence of the lactate/pyruvate shuttle and the appearance of oxaloacetate, malate and citrate outside mitochondria
Biochim. Biophys. Acta
1817
1679-1690
2012
Homo sapiens
Manually annotated by BRENDA team
Acharige, N.P.N.; Pflum, M.K.H.
L-lactate dehydrogenase identified as a protein tyrosine phosphatase 1B substrate by using K-BIPS
ChemBioChem
22
186-192
2021
Homo sapiens (P00338)
Manually annotated by BRENDA team
Liu, Z.; Li, J.; Li, M.; Chen, S.; Gao, R.; Zeng, G.; Chen, D.; Wang, S.; Li, Q.; Hu, D.; Zeng, W.; Guo, L.; Wu, X.
Elevated alpha-hydroxybutyrate dehydrogenase as an independent prognostic factor for mortality in hospitalized patients with COVID-19
ESC Heart Fail.
8
644-651
2021
Homo sapiens
Manually annotated by BRENDA team
Yu, H.; Han, H.; Li, J.; Li, D.; Jiang, L.
Alpha-hydroxybutyrate dehydrogenase as a biomarker for predicting systemic lupus erythematosus with liver injury
Int. Immunopharmacol.
77
105922
2019
Homo sapiens
Manually annotated by BRENDA team
Lee, S.; Koppensteiner, R.; Kopp, C.W.; Gremmel, T.
alpha-Hydroxybutyrate dehydrogenase is associated with atherothrombotic events following infrainguinal angioplasty and stenting
Sci. Rep.
9
18200
2019
Homo sapiens
Manually annotated by BRENDA team