Information on EC 1.8.1.4 - dihydrolipoyl dehydrogenase

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

EC NUMBER
COMMENTARY hide
1.8.1.4
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RECOMMENDED NAME
GeneOntology No.
dihydrolipoyl dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
protein N6-(dihydrolipoyl)lysine + NAD+ = protein N6-(lipoyl)lysine + NADH + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
redox reaction
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reduction
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
(S)-3-methyl-2-oxopentanoate dehydrogenase (acylating)
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2-oxoglutarate decarboxylation to succinyl-CoA
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2-oxoglutarate dehydrogenase complex
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2-oxoisovalerate decarboxylation to isobutanoyl-CoA
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4-methyl-2-oxopentanoate dehydrogenase (acylating)
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acetyl CoA biosynthesis
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Biosynthesis of antibiotics
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Biosynthesis of secondary metabolites
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Citrate cycle (TCA cycle)
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citric acid cycle
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glycine cleavage
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glycine metabolism
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Glycine, serine and threonine metabolism
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Glycolysis / Gluconeogenesis
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Metabolic pathways
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Microbial metabolism in diverse environments
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oxidative decarboxylation of pyruvate
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Propanoate metabolism
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pyruvate decarboxylation to acetyl CoA
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Pyruvate metabolism
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Valine, leucine and isoleucine degradation
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SYSTEMATIC NAME
IUBMB Comments
protein-N6-(dihydrolipoyl)lysine:NAD+ oxidoreductase
A flavoprotein (FAD). A component of the multienzyme 2-oxo-acid dehydrogenase complexes. In the pyruvate dehydrogenase complex, it binds to the core of EC 2.3.1.12, dihydrolipoyllysine-residue acetyltransferase, and catalyses oxidation of its dihydrolipoyl groups. It plays a similar role in the oxoglutarate and 3-methyl-2-oxobutanoate dehydrogenase complexes. Another substrate is the dihydrolipoyl group in the H-protein of the glycine-cleavage system ({AminoAcid/GlyCleave} for diagram), in which it acts, together with EC 1.4.4.2, glycine dehydrogenase (decarboxylating), and EC 2.1.2.10, aminomethyltransferase, to break down glycine. It can also use free dihydrolipoate, dihydrolipoamide or dihydrolipoyllysine as substrate. This enzyme was first shown to catalyse the oxidation of NADH by methylene blue; this activity was called diaphorase. The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein [6].
CAS REGISTRY NUMBER
COMMENTARY hide
9001-18-7
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
ecotypes Col-0 and Col-2
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Manually annotated by BRENDA team
Azotobacter agilis
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Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
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-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Uniprot
Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
strain Crookes
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Manually annotated by BRENDA team
strains AH242 SE2378 and SE2382
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Manually annotated by BRENDA team
strain M191-6
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Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
Mus musculus C57/Bl-6
C57/Bl-6 mice
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Manually annotated by BRENDA team
no activity in Escherichia coli
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Manually annotated by BRENDA team
no activity in Mycobacterium smegmatis
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
3D7, 2 lipdh genes encoding 2 isozymes in mitochondrion and apicoplast, both indispensable components of the 2-ketoacid dehydrogenase multienzyme complexes
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
strain PpG2
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
ATCC 27405T
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
Starkeyomyces koorchalomoides
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Manually annotated by BRENDA team
Starkeyomyces koorchalomoides FDUS 0337
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
PCC6803
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Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
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enzyme is inactivated by complex III- but not complex I-derived reactive oxygen species, and the accompanying loss of activity due to the inactivation can be restored by cysteine and glutathione. H2O2 instead of superoxide anion is responsible for the inactivation, and protein sulfenic acid formation is associated with the loss of enzymatic activity
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1,4-benzoquinone + NADH
1,4-benzoquinol + NAD+
show the reaction diagram
1-methoxy phenazine methosulfate + NADH
? + NAD+
show the reaction diagram
2 ferricyanide + NADH
2 ferrocyanide + NAD+ + H+
show the reaction diagram
2 ferricytochrome c + NADH
2 ferrocytochrome c + NAD+ + H+
show the reaction diagram
-
cytochrome c is a poor electron acceptor, only in presence of methylene blue the enzyme shows some activity
-
-
?
2,6-dichlorophenolindophenol + NADH
? + NAD+
show the reaction diagram
2,6-dimethoxy-1,4-benzoquinone + NADH
? + NAD+
show the reaction diagram
8.0% activity compared to lipoamide
-
-
?
2,6-dimethyl-1,4-benzoquinone + NADH
2,6-dimethyl-1,4-benzoquinol + NAD+
show the reaction diagram
2-(p-iodophenyl)-3-p-nitrophenyl-5-phenyltetrazolium chloride + NADH
? + NAD+
show the reaction diagram
-
-
-
?
2-hydroxy-1,4-benzoquinone + NADH
2-hydroxy-1,4-benzoquinol + NAD+
show the reaction diagram
-
-
-
-
?
2-methyl-1,4-benzoquinone + NADH
2-methyl-1,4-benzoquinol + NAD+
show the reaction diagram
-
-
-
-
?
2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide + NADH
?
show the reaction diagram
3-nitrotyrosine + dihydrolipoic acid
3-aminotyrosine + lipoic acid + H2O
show the reaction diagram
3-nitrotyrosine + NAD(P)H
3-aminotyrosine + NAD(P)+ + H2O
show the reaction diagram
-
-
-
-
?
3-nitrotyrosine + NADPH
3-aminotyrosine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
3-nitrotyrosine + ubiquinol
3-aminotyrosine + ubiquinone + H2O
show the reaction diagram
5,5'-dithiobis-(2-nitrobenzoic acid) + NADH + H+
? + NAD+
show the reaction diagram
5-hydroxy-1,4-naphthoquinone + NADH
5-hydroxy-1,4-naphthoquinol + NAD+
show the reaction diagram
-
-
-
-
?
5-nitroblue tetrazolium chloride + NADH
? + NAD+
show the reaction diagram
-
5.1% of the activity with lipoamide
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-
?
8-nitroguanine + dihydrolipoic acid
8-aminoguanine + lipoic acid + H2O
show the reaction diagram
8-nitroguanine + NAD(P)H
8-aminoguanine + NAD(P)+ + H2O
show the reaction diagram
-
-
-
-
?
8-nitroguanine + NADPH
8-aminoguanine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
8-nitroguanine + ubiquinol
8-aminoguanine + ubiquinone + H2O
show the reaction diagram
8-nitroxanthine + dihydrolipoic acid
8-aminoxanthine + lipoic acid + H2O
show the reaction diagram
8-nitroxanthine + NAD(P)H
8-aminoxanthine + NAD(P)+ + H2O
show the reaction diagram
-
-
-
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?
8-nitroxanthine + NADPH
8-aminoxanthine + NADP+ + H2O
show the reaction diagram
-
-
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?
8-nitroxanthine + ubiquinol
8-aminoxanthine + ubiquinone + H2O
show the reaction diagram
acetaldoxime + NADH
?
show the reaction diagram
alpha-lipoamide + NADH
dihydrolipoamide + NAD+
show the reaction diagram
alpha-lipoamide + NADH + H+
dihydrolipoamide + NAD+
show the reaction diagram
alpha-lipoic acid + NADH + H+
dihydrolipoic acid + NAD+
show the reaction diagram
benzyl viologen + NADH
? + NAD+
show the reaction diagram
-
2.9% of the activity with lipoamide
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-
?
coenzyme Q-10 + NADPH
ubiquinol + NADP+
show the reaction diagram
dihydrolipoamide + NAD+
lipoamide + NADH
show the reaction diagram
dihydrolipoamide + NAD+
lipoamide + NADH + H+
show the reaction diagram
dihydrolipoamide + NADP+
lipoamide + NADPH
show the reaction diagram
-
-
-
r
DL-6,8-thiooctic acid amide + NADH
? + NAD+
show the reaction diagram
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r
DL-alpha-lipoamide + NADH
dihydrolipoamide + NAD+
show the reaction diagram
-
-
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?
DL-lipoamide + NADH
DL-dihydrolipoamide + NAD+
show the reaction diagram
DL-lipoate + NADH
? + NAD+
show the reaction diagram
-
-
-
-
?
DL-lipoylbutanoate + NADH
? + NAD+
show the reaction diagram
-
-
-
-
?
DL-lipoylpentanoate + NADH
? + NAD+
show the reaction diagram
-
100fold reaction by the enzyme in two-electron-reduced state compared to the enzyme in four-electron-reduced state
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-
?
ferrocene + NADH
? + NAD+
show the reaction diagram
3.6% activity compared to lipoamide
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-
?
ferrocenecarboxylic acid + NADH
? + NAD+
show the reaction diagram
4.1% activity compared to lipoamide
-
-
?
formaldoxime + NADH
?
show the reaction diagram
glycerol trinitrate + NADH
?
show the reaction diagram
hexacyanoferrate + NADH
? + NAD+
show the reaction diagram
-
-
-
-
?
hydroxylamine hydrochloride + NADH
?
show the reaction diagram
iodonitrotetrazolium + NADH
? + NAD+
show the reaction diagram
-
-
-
-
?
iodonitrotetrazolium chloride + NADH
? + NAD+
show the reaction diagram
19.3% activity compared to lipoamide
-
-
?
lipoamide + 3-acetylpyridine adenine dinucleotide
dihydrolipoamide + ?
show the reaction diagram
-
-
-
-
?
lipoamide + NADH
dihydrolipoamide + NAD+
show the reaction diagram
lipoamide + NADH + H+
dihydrolipoamide + NAD+
show the reaction diagram
lipoamide + nicotinamide hypoxanthine dinucleotide
dihydrolipoamide + ?
show the reaction diagram
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-
-
-
?
lipoamide + thio-NADH
dihydrolipoamide + thio-NAD+
show the reaction diagram
-
-
-
-
?
lipoic acid + NADH
dihydrolipoic acid + NAD+
show the reaction diagram
mature frataxin + NADH
denoted frataxin + NAD+
show the reaction diagram
menadione + NADH
? + NAD+
show the reaction diagram
methylene blue + NADH
? + NAD+
show the reaction diagram
metmyoglobin + NADH
reduced myoglobin + NAD+
show the reaction diagram
-
myoglobin is a poor electron acceptor, only in presence of methylene blue the enzyme shows some activity
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-
?
NADH + H+ + oxidized 2,6-dichlorophenolindophenol
NAD+ + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
NADPH + H+ + oxidized 2,6-dichlorophenolindophenol
NADP+ + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
-
?
naphthoquinone + NADH
1,4-naphthoquinol + NAD+
show the reaction diagram
nitrated DNA + NAD(P)H
?
show the reaction diagram
-
enzyme reduces DNA nitro adducts including 8-nitroguanine, 3-nitrotyrosine, and 8-nitroxanthine, which formed in presence of peroxynitrite and nitryl chloride present in inflamed tissues, the nitrated DNA adducts are unstable and undergo spontaneous depurination which can cause cancer, enzyme might be resonsible for reversing biological nitration processes
-
-
?
nitrated DNA + NADPH
DNA + NADP+ + H2O
show the reaction diagram
-
enzyme reduces DNA nitro adducts including 8-nitroguanine, 3-nitrotyrosine, and 8-nitroxanthine, which formed in presence of peroxynitrite and nitryl chloride present in inflamed tissues, the nitrated DNA adducts are unstable and undergo spontaneous depurination
-
-
?
nitric oxide + NADH
nitrate + NAD+
show the reaction diagram
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-
-
-
?
nitro blue tetrazolium + NADH
? + NAD+
show the reaction diagram
nitrotetrazolium blue + NADH
? + NAD+
show the reaction diagram
2.9% activity compared to lipoamide
-
-
?
O2 + NADH
?
show the reaction diagram
O2 + NADH
H2O2 + NAD+
show the reaction diagram
O2 + NADH + H+
H2O2 + NAD+
show the reaction diagram
-
-
-
-
?
oxidized lipoamide + NADH
reduced lipoamide + NAD+
show the reaction diagram
-
-
-
-
?
oxidized lipoic acid + NADH
reduced lipoic acid + NAD+
show the reaction diagram
-
-
-
-
?
pyruvate + NADH
?
show the reaction diagram
-
-
-
-
?
reduced DL-lipoamide + NAD+
oxidized DL-lipoamide + NADH
show the reaction diagram
-
-
-
-
r
reduced lipoamide + NAD+
oxidized lipoamide + NADH
show the reaction diagram
resazurin + NADH
? + NAD+
show the reaction diagram
155.8% activity compared to lipoamide
-
-
?
resorufin + NADH
? + NAD+
show the reaction diagram
19.1% activity compared to lipoamide
-
-
?
S-nitroso-N-acetylpenicillamine + NADH
?
show the reaction diagram
S-nitrosoglutathione + NADH
?
show the reaction diagram
sodium nitroprusside + NADH
?
show the reaction diagram
sulfonated tetrazolium + NADH
? + NAD+
show the reaction diagram
39.2% activity compared to lipoamide
-
-
?
tellurite + NADH
NAD+ + ?
show the reaction diagram
thio-NAD+ + NADH
thio-NADH + NAD+
show the reaction diagram
ubiquinone + NAD(P)H
ubiquinol + NAD(P)+
show the reaction diagram
ubiquinone-10 + NAD(P)H
ubiquinol-10 + NAD(P)+
show the reaction diagram
vitamin K5 + NADH
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
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
alpha-lipoamide + NADH + H+
dihydrolipoamide + NAD+
show the reaction diagram
dihydrolipoamide + NAD+
lipoamide + NADH
show the reaction diagram
nitrated DNA + NAD(P)H
?
show the reaction diagram
-
enzyme reduces DNA nitro adducts including 8-nitroguanine, 3-nitrotyrosine, and 8-nitroxanthine, which formed in presence of peroxynitrite and nitryl chloride present in inflamed tissues, the nitrated DNA adducts are unstable and undergo spontaneous depurination which can cause cancer, enzyme might be resonsible for reversing biological nitration processes
-
-
?
nitrated DNA + NADPH
DNA + NADP+ + H2O
show the reaction diagram
-
enzyme reduces DNA nitro adducts including 8-nitroguanine, 3-nitrotyrosine, and 8-nitroxanthine, which formed in presence of peroxynitrite and nitryl chloride present in inflamed tissues, the nitrated DNA adducts are unstable and undergo spontaneous depurination
-
-
?
reduced lipoamide + NAD+
oxidized lipoamide + NADH
show the reaction diagram
-
enzyme catalyzes the NAD+-dependent oxidation of dihydrolipoyl cofactors being covalently attached to the acyltransferase components of pyruvate dehydrogenase, 2-ketoglutarate dehydrogenase, and glycine reductase multienzyme complexes
-
-
r
ubiquinone + NAD(P)H
ubiquinol + NAD(P)+
show the reaction diagram
ubiquinone-10 + NAD(P)H
ubiquinol-10 + NAD(P)+
show the reaction diagram
-
reaction is important to protect the cell e.g. from oxidative stress
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Dihydrolipoic acid
NAD(P)H
ubiquinol
additional information
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cd2+
-
highly, specifically stimulating for ubiquinone reduction, optimal at 0.5 mM
Fe
-
amino acid sequence homology indicates the presence of a Fe-containing rubredoxin-like domain. The amount of iron is determined to be 1.1 molecule per rDiaA molecule by ICP atomic emission spectroscopy
KCl
-
maximal enzymatic activity at 2 to 3 M KCl
Mg2+
-
NADH-oxidation with free lipoic acid is strongly dependent on the addition of NAD+, EDTA, Mg2+ and cysteine, the reverse reaction with reduced lipoic acid and NAD+ does not show any requirement for cofactors
NaCl
-
completely inactive in absence of NaCl
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,3-bis(2-chloroethyl)-1-nitrourea
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after reduction of the oxidized form of enzyme to the two-electron-reduced state
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
-
at higher concentrations (2 mM) significantly inhibits the lipoamide dehydrogenase activity
1-methyl-4-phenylpyridinium
-
at lower concentrations (1 mM) as compared to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine significantly inhibits the lipoamide dehydrogenase activity
10-(2-dimethylaminopropyl)-dibenzothiazine cation radical
-
60% inactivation after 10 min incubation and 79% after 30 min using the myeloperoxidase system, 72% inactivation after 10 min incubation using the horseradish peroxidase system
10-(2-methyl,3-dimethylaminopropyl)-dibenzothiazine cation radical
-
90% inactivation after 10 min and 30 min incubation using the myeloperoxidase system, 94% inactivation after 10 min incubation using the horseradish peroxidase system
10-(3-dimethylaminopropyl)-dibenzothiazine cation radical
-
87% inactivation after 10 min incubation and 89% after 30 min using the myeloperoxidase system, 94% inactivation after 10 min incubation using the horseradish peroxidase system
2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine hydrochloride
-
inhibition of NADH-lipoamide oxidoreductase activity, no effect on diaphorase activity and transhydrogenase activity
2-amino-4-hydroxy-6,7-dimethyl-7,8-dihydropteridine
-
inhibition of NADH-lipoamide oxidoreductase activity, no effect on diaphorase activity and transhydrogenase activity
2-amino-4-hydroxy-6-methyl-7,8-dihydropteridine
-
inhibition of NADH-lipoamide oxidoreductase activity, no effect on diaphorase activity and transhydrogenase activity
2-chloro-10-(3-dimethylaminopropyl)-dibenzothiazine cation radical
-
45% inactivation after 10 min incubation and 75% after 30 min using the myeloperoxidase system, 89% inactivation after 10 min incubation using the horseradish peroxidase system
2-chloro-10-[3-(1-methyl-4-piperazinyl)-propyl]-dibenzothiazine cation radical
-
54% inactivation after 10 min incubation and 80% after 30 min using the myeloperoxidase system, 90% inactivation after 10 min incubation using the horseradish peroxidase system
2-chloro-10-[3-[1-(2-hydroxyethyl)-4-piperazinyl]propyl]-dibenzothiazine cation radical
-
42% inactivation after 10 min incubation and 69% after 30 min using the myeloperoxidase system, 79% inactivation after 10 min incubation using the horseradish peroxidase system
2-methylmercapto-10-[2-(1-methyl-2-piperidinyl)-ethyl]-dibenzothiazine cation radical
-
77% inactivation after 10 min incubation and 82% after 30 min using the myeloperoxidase system, 85% inactivation after 10 min incubation using the horseradish peroxidase system
2-propionyl-10-(3-dimethylaminopropyl)-dibenzothiazine cation radical
-
11% inactivation after 10 min incubation and 32% after 30 min using the myeloperoxidase system, 83% inactivation after 10 min incubation using the horseradish peroxidase system
2-trifluoromethyl-10-[3-(1-methyl-4-piperazinyl)propyl]-dibenzothiazine cation radical
-
5% inactivation after 10 min incubation and 16% after 30 min using the myeloperoxidase system, 67% inactivation after 10 min incubation using the horseradish peroxidase system
2-trifluoromethyl-10-[3-(dimethylamino)propyl]-dibenzothiazine cation radical
-
2% inactivation after 10 and 30 min incubation using the myeloperoxidase system, 16% inactivation after 10 min incubation using the horseradish peroxidase system
2-trifluoromethyl-10-[3-[1-(2-hydroxyethyl)4-piperazinyl]propyl]-dibenzothiazine cation radical
-
1% inactivation after 10 min incubation and 8% after 30 min using the myeloperoxidase system, 61% inactivation after 10 min incubation using the horseradish peroxidase system
2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]-N-[3-(trifluoromethyl)benzyl]acetamide
-
5-methoxyindole-2-carboxylic acid
Angeli's salt
-
at 2 mM, induces a 90% loss in DLDH diaphorase activity
arsenite
Cd2+
-
in presence of NADH, inhibition is reversed by dithiols and less effectively by monothiols
chlorpromazine
-
0.1 mM, 75% inactivation, in the presence of 0.5 U/ml myeloperoxidase and 0.1 mM H2O2 at pH 7.4, 94% inactivation, in the presence of 0.005 mM myoglobin and 0.25 mM H2O2 at pH 7.4, 89% inactivation in the presence of 0.5 U/ml horseradish peroxidase and 0.2 mM H2O2 at pH 7.4
Diethylamine NONOate
-
induces 71% loss in diaphorase activity at 10 mM, but does not induce any activity loss at 2 mM
Dihydrolipoamide
-
-
diisopropyl fluorophosphate
diphenyleneiodonium chloride
Fe2+
-
at high concentrations has significant inhibitory effect on the lipoamide dehydrogenase activity
fluphenazine
-
0.1 mM, 53% inactivation, in the presence of 0.005 mM myoglobin and 0.25 mM H2O2 at pH 7.4, 61% inactivation in the presence of 0.5 U/ml horseradish peroxidase and 0.2 mM H2O2 at pH 7.4
folic acid
-
inhibition of NADH-lipoamide oxidoreductase activity, no effect on diaphorase activity and transhydrogenase activity
Guanidine-HCl
-
4C: 50% inactivation at 1.0 M, complete inactivation at 1.6 M, reversible
H2O2
-
enzyme is inactivated by complex III- but not complex I-derived reactive oxygen species, and the accompanying loss of activity due to the inactivation can be restored by cysteine and glutathione. H2O2 instead of superoxide anion is responsible for the inactivation, and protein sulfenic acid formation is associated with the loss of enzymatic activity
Hg2+
1 mM shows strong inhibitory effect on recombinant rBfmBC activity (more than 80% inhibition)
iodoacetic acid
-
in presence of NADH or dihydrolipoamide
isobiopterin
-
inhibition of NADH-lipoamide oxidoreductase activity, no effect on diaphorase activity and transhydrogenase activity
-
N-ethylmaleimide
N-[2-(2,4-dichlorophenyl)ethyl]-2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]acetamide
most potent inhibitor, noncompetitive versus NADH, NAD+, and lipoamide
NAD(P)+
-
product inhibition
p-Aminophenyldichloroarsine
p-[(bromoacetyl)-amino]phenyl arsenoxide
-
irreversible active site directed inactivation
Pb2+
1 mM shows strong inhibitory effect on recombinant BfmBC activity (more than 80% inhibition)
PCMB
-
0.1 mM, 50% inhibition
perphenazine
-
0.1 mM, 69% inactivation, in the presence of 0.5 U/ml myeloperoxidase and 0.1 mM H2O2 at pH 7.4, 75% inactivation, in the presence of 0.005 mM myoglobin and 0.25 mM H2O2 at pH 7.4, 79% inactivation in the presence of 0.5 U/ml horseradish peroxidase and 0.2 mM H2O2 at pH 7.4
phenothiazine cation radicals
-
irreversible inactivation dependent on time, radical structure, and radical production enzyme system, radicals are produced by reaction of myeloperoxidase or horse radish peroxidase on the phenothiazines promazine, trimeprazine, thioridazine, chlorpromazine, prochlorperazine, promethazine, and others, in presence of H2O2, protection by radical scavengers e.g. thiol compounds, amino acids and peptides, pyridine dinucleotides like NADH, or best by ascorbate and trolox, overview
potassium phosphate
-
when purified DLDH is eluted directly into potassium phosphate buffer, the enzymatic activity rapidly decreases
prochlorperazine
-
0.1 mM, 80% inactivation, in the presence of 0.5 U/ml myeloperoxidase and 0.1 mM H2O2 at pH 7.4, 85% inactivation, in the presence of 0.005 mM myoglobin and 0.25 mM H2O2 at pH 7.4, 80% inactivation in the presence of 0.5 U/ml horseradish peroxidase and 0.2 mM H2O2 at pH 7.4
promazine
-
0.1 mM, 89% inactivation, in the presence of 0.5 U/ml myeloperoxidase and 0.1 mM H2O2 at pH 7.4, 93% inactivation, in the presence of 0.005 mM myoglobin and 0.25 mM H2O2 at pH 7.4, 94% inactivation in the presence of 0.5 U/ml horseradish peroxidase and 0.2 mM H2O2 at pH 7.4, 94% inhibition in the presence of 0.2 mM NADH, 0.5 U/ml myeloperoxidase and 0.1 mM H2O2 after 10 min incubation
Promethazine
-
0.1 mM, 79% inactivation, in the presence of 0.5 U/ml myeloperoxidase and 0.1 mM H2O2 at pH 7.4, 51% inactivation, in the presence of 0.005 mM myoglobin and 0.25 mM H2O2 at pH 7.4, 72% inactivation in the presence of 0.5 U/ml horseradish peroxidase and 0.2 mM H2O2 at pH 7.4
propericyazine
-
0.1 mM, 40% inactivation, in the presence of 0.005 mM myoglobin and 0.25 mM H2O2 at pH 7.4
propionylpromazine
-
0.1 mM, 32% inactivation, in the presence of 0.5 U/ml myeloperoxidase and 0.1 mM H2O2 at pH 7.4, 88% inactivation, in the presence of 0.005 mM myoglobin and 0.25 mM H2O2 at pH 7.4, 83% inactivation in the presence of 0.5 U/ml horseradish peroxidase and 0.2 mM H2O2 at pH 7.4
S-nitrosocysteine
-
induces a 62% loss in diaphorase activity at 2 mM and an 88% loss at 10 mM
S-nitrosoglutathione
-
induces 84% loss in diaphorase activity at 10 mM, but does not induce any activity loss at 2 mM
thioridazine
-
0.1 mM, 82% inactivation, in the presence of 0.5 U/ml myeloperoxidase and 0.1 mM H2O2 at pH 7.4, 97% inactivation, in the presence of 0.005 mM myoglobin and 0.25 mM H2O2 at pH 7.4, 85% inactivation in the presence of 0.5 U/ml horseradish peroxidase and 0.2 mM H2O2 at pH 7.4, 85% inhibition in the presence of 0.1 mM NADH, 0.5 U/ml myeloperoxidase and 0.1 mM H2O2 after 10 min incubation
Trifluoperazine
-
0.1 mM, 16% inactivation, in the presence of 0.5 U/ml myeloperoxidase and 0.1 mM H2O2 at pH 7.4, 72% inactivation, in the presence of 0.005 mM myoglobin and 0.25 mM H2O2 at pH 7.4, 67% inactivation in the presence of 0.5 U/ml horseradish peroxidase and 0.2 mM H2O2 at pH 7.4
triflupromazine
-
0.1 mM, 68% inactivation, in the presence of 0.005 mM myoglobin and 0.25 mM H2O2 at pH 7.4, 16% inactivation in the presence of 0.5 U/ml horseradish peroxidase and 0.2 mM H2O2 at pH 7.4
trimeprazine
-
0.1 mM, 90% inactivation, in the presence of 0.5 U/ml myeloperoxidase and 0.1 mM H2O2 at pH 7.4, 90% inactivation, in the presence of 0.005 mM myoglobin and 0.25 mM H2O2 at pH 7.4, 94% inactivation in the presence of 0.5 U/ml horseradish peroxidase and 0.2 mM H2O2 at pH 7.4
valproyl-CoA
-
competitive inhibitor, 0.5-1.0 mM inhibit DLDH activity
valproyl-dephosphoCoA
-
uncompetitive inhibitor, 0.5-1.0 mM inhibit DLDH activity
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cysteine
-
NADH-oxidation with free lipoic acid is strongly dependent on the addition of NAD+, EDTA, Mg2+ and cysteine, the reverse reaction with reduced lipoic acid and NAD+ does not show any requirement for cofactors
dithiothreitol
-
presence during purification preserves enzymatic activity
EDTA
-
NADH-oxidation with free lipoic acid is strongly dependent on the addition of NAD+, EDTA, Mg2+ and cysteine, the reverse reaction with reduced lipoic acid and NAD+ does not show any requirement for cofactors
Guanidine-HCl
-
4C: activates the enzyme 2.5fold at 0.2 M
KCl
-
4C: activates the enzyme at concentrations below 1 M
lipoic acid
-
increase in activity might be due to formation of dihydrolipoic acid in the assay system
methylene blue
-
stimulates reduction of cytochrome c and myoglobin
NaCl
-
4C: activates the enzyme at concentrations below 1 M
NAD+
0.2 mM NAD+ demonstrates a strong activating effect on LPD, and the activity is 5.2 times higher than that without NAD+
ubiquinone
-
slight increase in activity might be due to formation of ubiquinol in the assay system
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01 - 0.4
1,4-benzoquinone
0.05
1,4-Naphthoquinone
-
-
0.015 - 0.12
2,6-dichlorophenolindophenol
0.86
2,6-dimethyl-1,4-benzoquinone
-
-
0.46 - 1.45
2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide
0.39
3-acetylpyridine adenine dinucleotide
-
-
0.29
5-hydroxy-1,4-naphthoquinone
-
-
0.96
acetaldoxime
-
in 50 mM Tris-HCl buffer (pH 7.6), at 37C
3.63
alpha-lipoamide
Starkeyomyces koorchalomoides
-
in 0.1 mM Tris-HCl (pH 7.0), 0.0005 mM EDTA, 0.01 mM beta2-mercaptoethanol, at 37C
0.0107 - 43.6
Dihydrolipoamide
4.7
dihydrolipoate
-
-
0.029
ferric leghemoglobin
-
-
2.73 - 17.82
formaldoxime
0.9 - 16.93
glycerol trinitrate
0.027
H-protein
-
-
-
3.24
Hydroxylamine hydrochloride
-
in 50 mM Tris-HCl buffer (pH 7.6), at 37C
0.05 - 16
Lipoamide
2.9 - 120
lipoate
2.1 - 2.15
lipoic acid
0.037 - 1.83
NAD+
0.00315 - 84
NADH
0.35
NADPH
-
recombinant DiaA
2.6
nicotinamide hypoxanthine dinucleotide
-
-
0.5
Nitro blue tetrazolium
-
recombinant DiaA
0.0005
NO
-
nitric oxide reduction, pH 7.5
0.3 - 0.48
pyruvate
0.5
R,S-lipoamide
-
-
-
0.42 - 5.48
S-nitroso-N-acetylpenicillamine
0.12 - 0.44
S-nitrosoglutathione
0.84 - 2.26
sodium nitroprusside
0.036
thio-NAD+
-
reaction with NADH
0.11
thio-NADH
-
-
additional information
additional information