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Information on EC 1.6.2.2 - cytochrome-b5 reductase
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1.6.2.2 cytochrome-b5 reductaseIUBMB Comments
A flavoprotein (FAD).
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Word Map
- 1.6.2.2
- erythrocyte
- methemoglobinemia
-
nadph-cytochrome
- hereditary
- reductases
-
cyanosis
- fad
- ferricyanide
- flavoproteins
-
desaturation
- dt-diaphorase
- aniline
-
amidoxime
-
methb
-
hemolysate
-
bioreductive
- n-demethylase
- aminopyrine
-
marc
-
n-hydroxylated
-
mixed-function
-
nadh-binding
- methaemoglobin
- medicine
-
oxyhemoglobin
- diagnostics
- analysis
- industry
- drug development
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
nadh-cytochrome b5 reductase, cytochrome b5 reductase, methemoglobin reductase, cyb5r3, ncb5or, nadh cytochrome b5 reductase, nadh:cytochrome b5 reductase, cyb5r2, cytochrome-b5 reductase, cyb5r, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
B5R
cb5r
CBR
CBR1
CyB5R
CYB5R3
cytochrome b5 reductase
cytochrome b5 reductase 3
dihydronicotinamide adenine dinucleotide-cytochrome b5 reductase
-
-
-
-
NADH cytochrome B5 reductase
NADH-cytochrome b5 reductase
NADH-cytochrome-b5 reductase
-
-
-
-
NADH-dependent cytochrome b5 reductase
NADH-ferricyanide reductase
NADH-ferricytochrome b5 oxidoreductase
-
-
-
-
NADH:cytochrome b5 reductase
NADH:ferricytochrome b5 oxidoreductase
P34/P32
-
-
-
-
P35
-
-
-
-
reduced nicotinamide adeninedinucleotide-cytochrome b5 reductase
-
-
-
-
reductase, cytochrome b5
-
-
-
-
B5R
-
-
-
-
cytochrome b5 reductase
-
-
-
-
NADH-cytochrome b5 reductase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5
ordered bi bi mechanism
-
NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5
hypothetical mechanism
-
NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5
hypothetical mechanism
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NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5
hypothetical mechanism
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NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5
hypothetical mechanism
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NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5
electron-transport chain from NADH to a terminal oxidase desaturase, proposed electron transfer mechanism
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NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5
reaction mechanism, overview
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NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5
Y93 forms contact with the FAD, but neither P92 nor Y93 preceeding the conserved motif RxYTSxxSN coordinating flavin binding are critical for flavin incorporation
NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
NADH:ferricytochrome-b5 oxidoreductase
A flavoprotein (FAD).
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CAS REGISTRY NUMBER
COMMENTARY
9032-25-1
-
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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
1,2-dihydro-8-(4-methylpiperazin-1-yl)-4-phenylimidazol[3,2-e]pyrazine 5-oxide + NADH
1,2-dihydro-8-(4-methylpiperazin-1-yl)-4-phenylimidazol[3,2-e]pyrazine + NAD+
-
potential bioreductive drug, trivial name RB90740
-
?
2 ferricytochrome b5 + NADPH
2 ferrocytochrome b5 + NADP+ + H+
with NADPH the enzyme shows about 20% of the activity with NADH
-
-
?
2-[4-iodophenyl]-3-[4-nitrophenyl]-5-[2,4-disulfophenyl]-2H tetrazolium monosodium salt + NADH
?
-
-
-
?
aquacobalamin + NADH
reduced aquacobalamin + NAD+
-
in the presence of outer membrane cytochrome b, no activity with cyanocobalamin
-
?
Fe3+-ammonium sulfate + NADH
Fe2+-ammonium sulfate + NAD+
-
strongly elevated by the addition of cytochrome b5
-
?
Fe3+-histidine + NADH
Fe2+-histidine + NAD+
-
strongly elevated by the addition of cytochrome b5
-
?
Fe3+-nitrilotriacetate + NADH
Fe2+-nitrilotriacetate + NAD+
-
in the presence of cytochrome b5, iron chelate reduction in descending order: Fe3+-nitrolotriacetate, Fe3+-ADP, Fe3+-diphosphate, Fe3+-citrate
-
?
ferricytochrome b5 + 4-(5-(4-[amino(hydroxyamino)methyl]phenyl)-2-furyl)-N'-hydroxybenzenecarboximidamide
ferrocytochrome b5 + ?
-
metabolite of DB289, an antimicrobial prodrug of furamidine
-
-
?
ferricytochrome b5 + 4-(5-(4-[amino(hydroxyamino)methyl]phenyl)-2-furyl)-N'-methoxybenzenecarboximidamide
ferrocytochrome b5 + ?
-
metabolite of DB289, an antimicrobial prodrug of furamidine
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-
?
ferricytochrome b5 + N-hydroxy-2-amino-1-methyl-6-phenylimidazol[4,5-b]pyridine
ferrocytochrome b5 + ?
-
arylhydroxylamine carcinogen found in grilled meat
-
-
?
ferricytochrome b5 + N-hydroxy-4-aminobiphenyl
ferrocytochrome b5 + ?
-
arylhydroxylamine carcinogen found in cigarette smoke
-
-
?
methemoglobin-ferrocyanide complex + NADH
reduced methemoglobin-ferrocyanide complex + NAD+
-
-
-
?
NADH + ferricytochrome b5 + oxidized soluble guanylate cyclase
NAD+ + H+ + ferrocytochrome b5 + reduced soluble guanylate cyclase
-
-
-
-
?
NADH + oxidized 2,6-dichlorophenolindophenol
NAD+ + H+ + reduced 2,6-dichlorophenolindophenol
NADH + oxidized nitroblue tetrazolium
NAD+ + H+ + reduced nitroblue tetrazolium
-
-
-
-
?
sulfamethoxazole hydroxylamine + NADH
?
-
in the presence of cytochrome b5
-
-
?
2 ferricyanide + NADH
2 ferrocyanide + NAD+ + H+
-
-
-
-
?
2 ferricyanide + NADH
2 ferrocyanide + NAD+ + H+
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
specific for NADH as electron donor, artificial acceptors: ferricyanide, 2,6-dichlorphenolindophenol
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
no acceptors: ubiquinone-30, menadione, dihydrofolate, lipoamide
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
poor donor: NADPH
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
artificial acceptor: ferricyanide, high reactivity with NADPH as electron donor
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
specific for NADH as electron donor, artificial acceptors: ferricyanide, 2,6-dichlorphenolindophenol
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
specific for NADH as electron donor, artificial acceptors: ferricyanide, 2,6-dichlorphenolindophenol
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
specific for NADH as electron donor, artificial acceptors: ferricyanide, 2,6-dichlorphenolindophenol
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
specific for NADH as electron donor, artificial acceptors: ferricyanide, 2,6-dichlorphenolindophenol
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
poor electron acceptors: methylene blue, ferricytochrome c, O2, oxidized glutathione, methemoglobin
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?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
artificial electron acceptor in the presence of menadione: cytochrome c
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?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
additional electron donors: deamino-NADH, 3-acetylpyridine-NADH
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-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
artificial acceptors: p-benzoquinone, 5-hydroxy-1,4-naphthoquinone, nitroblue-tetrazolium
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
additional acceptor: methemoglobin-ferrocyanide complex
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
involved in metabolism of endogenous compounds such as steroids, drugs, carcinogens, environmental pollutants
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
enzyme participates in methemoglobin reduction in erythrocytes, in other tissues it plays a role in elongation and desaturation of fatty acids, P-450 mediated drug metabolism and cholesterol biosynthesis as part of the microsomal electron transfer system
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
soluble form of erythrocytes: reduction of methemoglobin
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?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
soluble form of erythrocytes: reduction of methemoglobin
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?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
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involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics
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-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics, enzyme in presence of cytochrome b5 supports activity of CYP2E1
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics, participates in the regeneration of vitamin E and of ascorbate, maintains antioxidant levels and is therefore involved in the protection of membrane lipids from peroxidation, considered as a constitutive housekeeping enzyme
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-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
recessive congenital methaemoglobinaemia, is caused by NADH-cytochrome b5 reductase deficiency. Two distinct clinical forms, types I and II, are recognized, both characterized by cyanosis from birth. In type II, the cyanosis is accompanied by neurological impairment and reduced life expectancy
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
the electrostatic interactions between the lysyl residues (K42, K126, K163, and K164) in the enzyme and the carboxyl groups (E47, E48, E52, E60, and D64) of cytochrome b5 keep the proteins tightly complexed and are suitable for electron transfer, reaction mechanism, overview
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-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
potassium ferricyanide, cytochrome b5, or NADH-2,6-dichlorophenol-indophenol can act as electron acceptors
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-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics, removal of reactive oxygen species
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
uses both NADH and NADPH as electron donors, artificial acceptors: ferricyanide, 2,6-dichlophenolindophenol
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
low activity with trypsin-solubilized cytochrome b5
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?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
specific for NADH as electron donor, artificial acceptors: ferricyanide, 2,6-dichlorphenolindophenol
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
specific for NADH as electron donor, artificial acceptors: ferricyanide, 2,6-dichlorphenolindophenol
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
specific for NADH as electron donor, artificial acceptors: ferricyanide, 2,6-dichlorphenolindophenol
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
specific for NADH as electron donor, artificial acceptors: ferricyanide, 2,6-dichlorphenolindophenol
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
additional acceptor: hemin
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?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
poor donor: NADPH
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?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
additional acceptor: methemoglobin-ferrocyanide complex
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?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
artificial acceptor: ferricyanide
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
additional acceptor: methemerythrin
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
specific for NADH as electron donor, artificial acceptors: ferricyanide, 2,6-dichlorphenolindophenol
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
recombinant enzyme, very low activity with NADPH
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
involved in desaturation of fatty acids
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics, enzyme defects causes methemoglobinemia type I or type II
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics, mutations can cause methemoglobinemia type I or II
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics, removal of reactive oxygen species
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
specific for NADH as electron donor, artificial acceptors: ferricyanide, 2,6-dichlorphenolindophenol
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
enzyme complex drives the entire sterol 14-demethylation reaction
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
involved in desaturation of fatty acids
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
membrane bound form of somatic cells: essential for lipid metabolism
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
enzyme is assumed to be part of an endoplasmic reticulum associated redox chain that oxidizes NADH to provide electrons via cytochrome b5 to endoplasmic reticulum associated fatty acyl desaturase and related hydroxylases as in mammals
-
?
2 ferricytochrome c + NADH
2 ferrocytochrome c + NAD+ + H+
-
increases in the presence of cytochrome b5
-
-
?
2 ferricytochrome c + NADH
2 ferrocytochrome c + NAD+ + H+
-
in the presence of outer membrane cytochrome b
-
?
2 ferricytochrome c + NADH
2 ferrocytochrome c + NAD+ + H+
-
cytochrome b5/cytochrome b5 reductase FAD-domain-fusion protein, NADPH is preferred
-
?
2 ferricytochrome c + NADH
2 ferrocytochrome c + NAD+ + H+
reduces also ferricyanide
-
?
2 ferricytochrome c + NADH
2 ferrocytochrome c + NAD+ + H+
isoforms I and II, 16% and 27% of Fe3+-citrate reduction respectively
-
?
2 ferricytochrome c + NADH
2 ferrocytochrome c + NAD+ + H+
isoforms I and II, 16% and 27% of Fe3+-citrate reduction respectively
-
?
Cu2+-citrate + NADH
Cu+-citrate + NAD+
isoforms I and II, 59 and 47% of Fe3+-citrate reduction respectively
-
?
Cu2+-citrate + NADH
Cu+-citrate + NAD+
isoforms I and II, 59 and 47% of Fe3+-citrate reduction respectively
-
?
Fe3+-ATP + NADH
Fe2+-ATP + NAD+
-
reconstituted system containing NADH, cytochrome b5 reductase, cytochrome b5 and microsomal lipids catalyzes lipid peroxidation in the presence of ferric-ATP, ferric-histidine and ferric-ammonium sulfate
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
-
r
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
-
r
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
r
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
-
r
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
?
NADH + oxidized 2,6-dichlorophenolindophenol
NAD+ + H+ + reduced 2,6-dichlorophenolindophenol
-
-
-
?
NADH + oxidized 2,6-dichlorophenolindophenol
NAD+ + H+ + reduced 2,6-dichlorophenolindophenol
-
-
-
?
NADH + oxidized 2,6-dichlorophenolindophenol
NAD+ + H+ + reduced 2,6-dichlorophenolindophenol
-
-
-
-
?
NADH + oxidized 2,6-dichlorophenolindophenol
NAD+ + H+ + reduced 2,6-dichlorophenolindophenol
-
-
-
-
r
NADH + oxidized 2,6-dichlorophenolindophenol
NAD+ + H+ + reduced 2,6-dichlorophenolindophenol
-
-
-
-
?
NADPH + ferricytochrome b5
NADP+ + H+ + ferrocytochrome b5
-
low affinity for NADPH
-
-
?
additional information
?
-
-
poor activity with the anticancer drug mitomycin C, no activity with anticancer drug idarubicin. The quinone antitumor agents are used in the treatment of several human neoplasms
-
-
?
additional information
?
-
-
role of enzyme in fatty acid desaturation and conjugation
-
-
?
additional information
?
-
role of enzyme in fatty acid desaturation and conjugation
-
-
?
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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
NADH + ferricytochrome b5 + oxidized soluble guanylate cyclase
NAD+ + H+ + ferrocytochrome b5 + reduced soluble guanylate cyclase
-
-
-
-
?
sulfamethoxazole hydroxylamine + NADH
?
-
in the presence of cytochrome b5
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
involved in metabolism of endogenous compounds such as steroids, drugs, carcinogens, environmental pollutants
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
enzyme participates in methemoglobin reduction in erythrocytes, in other tissues it plays a role in elongation and desaturation of fatty acids, P-450 mediated drug metabolism and cholesterol biosynthesis as part of the microsomal electron transfer system
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
soluble form of erythrocytes: reduction of methemoglobin
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
soluble form of erythrocytes: reduction of methemoglobin
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics, enzyme in presence of cytochrome b5 supports activity of CYP2E1
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics, participates in the regeneration of vitamin E and of ascorbate, maintains antioxidant levels and is therefore involved in the protection of membrane lipids from peroxidation, considered as a constitutive housekeeping enzyme
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
recessive congenital methaemoglobinaemia, is caused by NADH-cytochrome b5 reductase deficiency. Two distinct clinical forms, types I and II, are recognized, both characterized by cyanosis from birth. In type II, the cyanosis is accompanied by neurological impairment and reduced life expectancy
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
the electrostatic interactions between the lysyl residues (K42, K126, K163, and K164) in the enzyme and the carboxyl groups (E47, E48, E52, E60, and D64) of cytochrome b5 keep the proteins tightly complexed and are suitable for electron transfer, reaction mechanism, overview
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics, removal of reactive oxygen species
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
involved in desaturation of fatty acids
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics, enzyme defects causes methemoglobinemia type I or type II
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics, mutations can cause methemoglobinemia type I or II
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics, removal of reactive oxygen species
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
enzyme complex drives the entire sterol 14-demethylation reaction
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
involved in desaturation of fatty acids
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
involved in the synthesis of fatty acids and cholesterol, and in the oxidation of xenobiotics
-
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
-
membrane bound form of somatic cells: essential for lipid metabolism
-
?
2 ferricytochrome b5 + NADH
2 ferrocytochrome b5 + NAD+ + H+
enzyme is assumed to be part of an endoplasmic reticulum associated redox chain that oxidizes NADH to provide electrons via cytochrome b5 to endoplasmic reticulum associated fatty acyl desaturase and related hydroxylases as in mammals
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
-
?
NADH + ferricytochrome b5
NAD+ + H+ + ferrocytochrome b5
-
-
-
?
additional information
?
-
-
poor activity with the anticancer drug mitomycin C, no activity with anticancer drug idarubicin. The quinone antitumor agents are used in the treatment of several human neoplasms
-
-
?
additional information
?
-
-
role of enzyme in fatty acid desaturation and conjugation
-
-
?
additional information
?
-
role of enzyme in fatty acid desaturation and conjugation
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
calculated results suggest that the electron and/or hydride ion transfer reaction from NADH to FAD can be accelerated in the presence of heme(Fe3+)
FAD
cytochrome b5 reductase is composed of one FAD and one NADH binding domain linked by a hinge region
FAD
-
flavoprotein, the FAD domain has a large cleft in which the FAD prosthetic group is located. The N-terminus of the NADH domain plays a hinge-connecting role between the two domains, the FAD and the NADH domains
FAD
redox state of FAD during the b5R catalytic cycle and crystal structures comparion of the fully reduced form and the oxidized form, overview
FAD
the FAD cofactor is located in the cleft between the N-terminal FAD-binding domain and the C-terminal NADH-binding domain. The cofactor is located in the cleft between the two domains and interacts primarily with the FAD-binding domain
FAD
the FAD group of cytochrome b5 reductase increases its solvent exposition upon complex formation with cytochrome b5 promoting an efficient electron transfer between the proteins
NADH
-
-
392811, 394195, 394196, 394199, 394200, 394203, 394210, 394213, 394216, 394222, 394225, 394234, 394235, 657460, 657648, 659107, 659784, 672826, 713187
NADH
-
-
NADH
-
-
NADH
-
preferred electron donor for CyB5R, a D239T mutation will change this preference to one for NADPH. The NADH domain provides a suitable position for the NADH coenzyme. The N-terminus of the NADH domain plays a hinge-connecting role between the two domains, the FAD and the NADH domains
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
additional information
additional information
-
enzyme does not contain appreciable amounts of iron, copper, manganes, silver, mercury, lead, zinc, cobalt or nickel
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(5Z)-5-[(9H-fluoren-3-yl)methylidene]-1-(4-methylphenyl)-2-sulfanylidenedihydropyrimidine-4,6(1H,5H)-dione
about 80% inhibition at 0.5 mM
(5Z)-5-{[4-bromo-5-(morpholin-4-yl)furan-2-yl]methylidene}-1-(4-methylphenyl)-2-sulfanylidenedihydropyrimidine-4,6(1H,5H)-dione
about 5% inhibition at 0.5 mM
1-(2-fluorophenyl)-5-[(1-methyl-2,3-dihydro-1H-indol-3-yl)methyl]-2-sulfanylidenedihydropyrimidine-4,6(1H,5H)-dione
about 75% inhibition at 0.5 mM
2-methyl-6-[(phenylsulfanyl)methyl]-2,5-dihydropyrimidin-4(3H)-one
about 5% inhibition at 0.5 mM
4-({[(2S)-2,3-dihydro-1,3-benzoxazol-2-yl]sulfanyl}methyl)tetrahydropyrimidine-2,5-dione
about 45% inhibition at 0.5 mM
5-(prop-2-en-1-yl)-6-propyl-2-sulfanylidene-2,3-dihydropyrimidin-4(1H)-one
about 75% inhibition at 0.5 mM
6-(pentyloxy)-2-sulfanylidene-2,3-dihydropyrimidin-4(1H)-one
about 25% inhibition at 0.05 mM
6-([[(2R)-2,3-dihydro-1,3-benzoxazol-2-yl]sulfanyl]methyl)-2-sulfanylidene-2,3-dihydropyrimidin-4(1H)-one
complete inhibition at 0.05 mM
6-benzyl-2-sulfanylidene-2,3-dihydropyrimidin-4(1H)-one
about 3% inhibition at 0.5 mM
6-pentyl-2-sulfanylidene-2,3-dihydropyrimidin-4(1H)-one
about 25% inhibition at 0.5 mM
6-[(phenylsulfanyl)methyl]-2-sulfanylidene-2,3-dihydropyrimidin-4(1H)-one
complete inhibition at 0.05 mM
6-[(phenylsulfanyl)methyl]pyrimidine-2,4(1H,3H)-dione
about 50% inhibition at 0.5 mM
6-{[(2,6-dichlorophenyl)sulfanyl]methyl}-2-sulfanylidene-2,3-dihydropyrimidin-4(1H)-one
complete inhibition at 0.05 mM
6-{[(4-bromophenyl)sulfanyl]methyl}-2-sulfanylidene-2,3-dihydropyrimidin-4(1H)-one
about 10% inhibition at 0.05 mM
6-{[(4-methylphenyl)sulfanyl]methyl}-2-sulfanylidene-2,3-dihydropyrimidin-4(1H)-one
about 85% inhibition at 0.05 mM
6-{[(propan-2-yl)sulfanyl]methyl}-2-sulfanylidene-2,3-dihydropyrimidin-4(1H)-one
about 18% inhibition at 0.05 mM
benzyl alcohol
-
100 mM, 52% inhibition, reversible, may be due to changes in membrane fluidity
K+ high ionic strength
-
reduction of cytochrome b5 or dichlorphenolindophenol
-
myricetin
-
noncompetitive versus NADH, non-linear relationship indicating non-Michaelis-Menten kinetic binding with respect to cytochrome b5
NAD+
competitive, stronger inhibition of mutant enzymes compared to wild type enzyme
additional information
-
inhibitory potencies of flavonoids on the enzyme, structure-activity relationship, overview. No inhibition by naringenin, naringin, and chrysin. Flavonoids containing two hydroxyl groups in ring B and a carbonyl group at C-4 in combination with a double bond between C-2 and C-3 produced a much stronger inhibition, whereas substitution of a hydroxyl group at C-3 is associated with a less inhibitory effect
-
additional information
-
enzyme inhibition by dietary flavonoids: inhibitor structure-activity analysis, overview. No inhibition by morin, apigenin, (+)-catechin, (-)-epicatechin, naringenin and naringin
-
additional information
-
species-specific sensitivity to methemoglobin induction, in vitro induction of methemoglobin by 1 mM NaNO2, overview
-
additional information
-
the enzyme is not inhibited by Mg2+, Mn2+, or EDTA
-
additional information
-
species-specific sensitivity to methemoglobin induction, in vitro induction of methemoglobin by 1 mM NaNO2, overview
-
additional information
-
species-specific sensitivity to methemoglobin induction, in vitro induction of methemoglobin by 1 mM NaNO2, overview
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
detailed analysis of biphasic rate of reduction of cytochrome b5 in membranes. The initial rapid phase is completed within 10 msec and over 90% of cytochrome b5 are reduced in 40 msec. Evaluation of data in terms of two-dimensional random walk model
-
0.00104
ferricyanide
-
mutant enzyme P247L, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.00723
ferricyanide
-
wild type enzyme, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.008
ferricyanide
-
cytochrome b5/cytochrome b5 reductase FAD-domain fusion protein
0.01096
ferricyanide
-
mutant enzyme P247A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.01563
ferricyanide
-
mutant enzyme P248A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.01568
ferricyanide
-
mutant enzyme P248L, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.02646
ferricyanide
-
mutant enzyme P249A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.03309
ferricyanide
-
mutant enzyme P249L, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.01353
ferricytochrome b5
-
wild type enzyme, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.0207
ferricytochrome b5
-
mutant enzyme P247A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.03434
ferricytochrome b5
-
mutant enzyme P248A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.035
ferricytochrome b5
-
enzyme from liver microsome membrane, solubilized with Triton X-100
0.04481
ferricytochrome b5
-
mutant enzyme P249A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.045
ferricytochrome b5
-
enzyme from liver microsome membrane, cathepsin D solubilized
0.007
ferricytochrome c
-
cytochrome b5/cytochrome b5 reductase FAD-domain fusion protein
0.01097
NADH
-
wild type enzyme, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.0135
NADH
-
mutant enzyme P248L, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.0155
NADH
-
mutant enzyme P249L, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.01713
NADH
-
mutant enzyme P247A, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.02407
NADH
-
mutant enzyme P248A, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.02467
NADH
-
mutant enzyme P247L, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.02928
NADH
-
mutant enzyme P249A, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
0.001
NADPH
-
cytochrome b5/cytochrome b5 reductase FAD-domain fusion protein
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
21.7
ferricyanide
-
cytochrome b5/cytochrome b5 reductase FAD-domain fusion protein
30.8
ferricyanide
-
mutant enzyme P247L, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
337
ferricyanide
-
wild type enzyme, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
357
ferricyanide
-
mutant enzyme P247A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
399
ferricyanide
-
mutant enzyme P248A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
504
ferricyanide
-
mutant enzyme P248L, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
838
ferricyanide
-
mutant enzyme P249A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
1241
ferricyanide
-
mutant enzyme P249L, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
8.3
ferricytochrome b5
-
cytochrome b5/cytochrome b5 reductase FAD-domain fusion protein
147
ferricytochrome b5
-
wild type enzyme, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
167
ferricytochrome b5
-
mutant enzyme P247A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
301
ferricytochrome b5
-
mutant enzyme P248A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
540
ferricytochrome b5
-
mutant enzyme P249A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
21.7
NADH
-
mutant enzyme P247L, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
354
NADH
-
mutant enzyme P247A, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
540
NADH
-
mutant enzyme P248L, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
559
NADH
-
mutant enzyme P248A, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
681
NADH
-
mutant enzyme P249A, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
742
NADH
-
wild type enzyme, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
1059
NADH
-
mutant enzyme P249L, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
25530
ferricyanide
-
mutant enzyme P248A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
29620
ferricyanide
-
mutant enzyme P247L, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
31670
ferricyanide
-
mutant enzyme P249A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
32140
ferricyanide
-
mutant enzyme P248L, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
32570
ferricyanide
-
mutant enzyme P247A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
37500
ferricyanide
-
mutant enzyme P249L, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
46610
ferricyanide
-
wild type enzyme, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
80700
ferricytochrome b5
-
mutant enzyme P247A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
87700
ferricytochrome b5
-
mutant enzyme P248A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
108600
ferricytochrome b5
-
wild type enzyme, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
120500
ferricytochrome b5
-
mutant enzyme P249A, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
880
NADH
-
mutant enzyme P247L, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
20670
NADH
-
mutant enzyme P247A, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
23220
NADH
-
mutant enzyme P248A, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
23260
NADH
-
mutant enzyme P249A, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
40000
NADH
-
mutant enzyme P248L, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
67640
NADH
-
wild type enzyme, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
68320
NADH
-
mutant enzyme P249L, using ferricyanide as cosubstrate, in 100 mM potassium phosphate buffer (pH 7.0) at 25°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00914
6-([[(2R)-2,3-dihydro-1,3-benzoxazol-2-yl]sulfanyl]methyl)-2-sulfanylidene-2,3-dihydropyrimidin-4(1H)-one
Homo sapiens
at pH 7.5 and 37°C
0.0108
6-[(phenylsulfanyl)methyl]-2-sulfanylidene-2,3-dihydropyrimidin-4(1H)-one
Homo sapiens
at pH 7.5 and 37°C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00072
-
liver microsomes, reduction of 1,2-dihydro-8-(4-methylpiperazin-1-yl)-4-phenylimidazol[3,2-e]pyrazine 5-oxide
628
additional information
additional information
-
28.6 units, 1 unit is defined as the amount of enzyme changing 0.001 of DELTAAbsorbance/min
additional information
-
102.0 units/mg, 1 unit is defined as the change of 1 absorbance unit at 600 nm/min
additional information
-
41.25 units, 1 unit is defined as the amount of enzyme changing 0.001 of DELTAAbsorbance/min
additional information
-
enzyme activity in erythrocytes of mammalian enzymes and rainbow trout, overview
additional information
-
enzyme activity in erythrocytes of mammalian enzymes and rainbow trout, overview
additional information
-
enzyme activity in erythrocytes of mammalian enzymes and rainbow trout, overview
additional information
-
0.00017 mmol ferricyanide reduced/min/10000000 cells, activity in neutrophils
additional information
-
enzyme activity in erythrocytes of rainbow trout compared to mammalian enzymes, overview
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.4
7.5
additional information
-
no distinct optimum with phosphate or Tris-HCl buffer
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
30
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
-
-
-
brenda
-
392811, 394195, 394196, 394199, 394200, 394203, 394210, 394213, 394216, 394222, 394225, 394234, 394235, 394237, 394238, 394251, 657460, 657648
-
-
brenda
deficiency leads to 2 different types of recessive congenital methemoglobinemia, in type 1 the soluble enzyme in erythrocytes is affected, in type 2 both soluble and membrane-bound isoforms are affected
-
-
brenda
patients with recessive hereditary methemoglobinemia due to cytochrome b5 reductase deficiency
SwissProt
brenda
sequence of natural mutant gene from a patient with recessive congenital methemoglobinemia; patients with recessive congenital methemoglobinemia
SwissProt
brenda
cytochrome b5/cytochrome b5 reductase fusion protein, exists also as a variant where the whole exon 12 is deleted
SwissProt
brenda
-
-
-
brenda
antibodies against the liver enzyme activate NADH 5-alpha reductase
-
-
brenda
cytochrome b5/cytochrome b5 reductase fusion protein, exists also as a variant where the whole exon 12 is deleted
SwissProt
brenda
enzyme is expressed through the use of at least 4 different promotors
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
soluble form
brenda
Cytb5r enzyme activity is drastically reduced in all patients with recessive hereditary methemoglobinemia. Eight different mutations are detected among the twelve mutated alleles identified
brenda
-
NaCl application results in a significant increase in the activity
brenda
-
NaCl application results in a significant increase in the activity
brenda
-
-
brenda
additional information
exon 12 deletion variant is not found in kidney, lung, liver, and heart
brenda
additional information
-
exon 12 deletion variant is not found in kidney, lung, liver, and heart
brenda
additional information
exon 12 deletion variant is not found in kidney, lung, liver, and heart
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
possible conformation of membrane binding domain
-
brenda
-
2 forms in erythrocytes: a soluble and a membrane-bound enzyme which represents the majority
brenda
-
-
brenda
-
membrane-binding domain resides in the NH2-terminal region
brenda
-
enzyme binds in vitro to a variety of membrane preparations, protease treatment removes a hydrophobic segment that is responsible for membrane binding
brenda
-
microsomal enzyme, COOH-terminal domain constitutes the hydrophobic moiety which is responsible for membrane-binding
brenda
-
subcellular distribution, high concentration in outer mitochondrial membrane
brenda
-
membrane of endoplasmic reticulum, outer mitochondrial membrane, tightly bound to cytoplasmic face of membrane
brenda
-
full length form contains a 3 kDa membrane anchoring domain
brenda
full length form contains a 3 kDa membrane anchoring domain
brenda
-
the microsomal isozyme consists of one hydrophobic membrane-anchoring domain and a larger hydrophilic flavin catalytic domain
-
brenda
-
N-myristoylation is required for correct targeting
brenda
truncated form lacking the membrane anchoring domain, present in erythrocytes
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
CyB5R is a member of the NAD(P)H-ferredoxin reductase (FNR) enzyme superfamily, phylogenetic analysis
malfunction
metabolism
physiological function
additional information
malfunction
-
congenital methemoglobinemia due to deficiency of NADH-cytochrome b5 reductase is an autosomal recessive disorder characterized by life long cyanosis
malfunction
-
autosomal cytochrome b5 reductase gene deficiency manifests with the accumulation of oxidized Fe+3 and recessive congenital methemoglobinemia in humans. Diseases related to CyB5R dysfunctions, overviews
malfunction
-
the progeny of plants heterozygous for the cbr1-2 allele segregate 6% homozygous mutants, while cbr1-3 and cbr1-4 heterozygotes segregate 1:1 heterozygous:wild-type, indicating a gametophyte defect. Homozygous cbr1-2 seeds are deformed and required Suc for successful germination and seedling establishment. Vegetative growth of cbr1-2 plants was relatively normal, and they produced abundant flowers, but very few seeds. The pollen produced in cbr1-2 anthers is viable, but when germinated on cbr1-2 or wild-type stigmas, most of the resulting pollen tubes do not extend into the transmitting tract, resulting in a very low frequency of fertilization, phenotype, overview
malfunction
-
autosomal cytochrome b5 reductase gene deficiency manifests with the accumulation of oxidized Fe3+ and recessive congenital methemoglobinemia in humans
malfunction
-
recessive congenital methaemoglobinaemia is caused by a deficiency of NADH-cytochrome b5 reductase
malfunction
the cytochrome b5/cytochrome b5 reductase system is a viable reductant for cytoglobin in vivo
malfunction
-
the enzyme is required for desaturation to biosynthesize polyunsaturated fatty acids
metabolism
-
2e- transfer from NADH to the enzyme CyB5R, to FAD, followed by reduction of 2 CyB5 and electron transfer to desaturase, CyP450 or methemoglobin
metabolism
-
the quantity of methemoglobin is kept in balance by an efficient redox system within erythrocytes involving the enzyme, overview
metabolism
-
cytochrome b5/cytochrome b5 reductase can act as a sole electron donor to the P450 system in vitro and in vivo
metabolism
the enzyme is involved in fatty acid, sphingolipid and sterol metabolism
metabolism
-
the enzyme participates as an alternative electron donor pathway for P450 enzymes involved in ergosterol biosynthesis
metabolism
-
the NADH/cytochrome b5/enzyme system can act as the sole electron donor both for the first and second reduction of cytochrome P450 1A1 during the oxidation of benzo[a]pyrene in vitro
metabolism
an increase of cytochrome b5 reductase flavin autofluorescence is observed in the presence of cytochrome b5. A dissociation constant value between proteins of 0.5 microM and a 1:1 stoichiometry for the complex formation are calculated. A 30 mV negative shift of cytochrome b5 reductase redox potential in presence of cytochrome b5 is observed
metabolism
-
cytochrome b5 reductase mediates redox cycling of a variety of quinones generating superoxide anion, hydrogen peroxide, and, in the presence of transition metals, hydroxyl radicals. Redox cycling activity is oxygen-dependent and preferentially utilizes NADH as a cosubstrate. Quinone redox cycling inhibits reduction of cytochrome b5 by cytochrome b5 reductase under aerobic conditions
metabolism
the zebrafish cytochrome b5 reductase reduces zebrafish heme proteins cytoglobin 1 and 2 in presence of the two zebrafish cytochrome b5 isoforms. The reducing system also supports reduction of globin X, a conserved globin in fish and amphibians. The P50 for oxygen is 0.5 Torr for cytoglobin 1 and 4.4 Torr for cytoglobin 2 at 25°C
metabolism
-
the enzyme is involved in fatty acid, sphingolipid and sterol metabolism
-
metabolism
-
the enzyme participates as an alternative electron donor pathway for P450 enzymes involved in ergosterol biosynthesis
-
physiological function
-
cytochrome b5 reductase is responsible for the reduction of methemoglobin back to hemoglobin
physiological function
-
cytochrome b5 reductase encoded by CBR1 is essential for a functional male gametophyte in Arabidopsis thaliana. It provides electrons, via cytochrome b5, for a range of biochemical reactions in cellular metabolism, including for fatty acid desaturation in the endoplasmic reticulum. Cytochrome b5 reductase is not essential during vegetative growth but is required for correct pollen function and seed maturation
physiological function
-
cytochrome b5 reductase is involved in the transfer of reducing equivalents from the physiological electron donor, NADH, via an FAD domain to the small molecules of cytochrome b5. It takes part in many oxidation and reduction reactions, such as the reduction of methemoglobin to hemoglobin
physiological function
-
methemoglobin in rainbow trout erythrocytes can be reduced by NADH-dependent cytochrome b5 reductase, i.e. CB5R, or NADPH-dependent methemoglobin reductase. The nucleated red blood cells of rainbow trout use membrane-bound CB5R to reduce methemoglobin
physiological function
the enzyme catalyzes the electron transfer from NADH to cytochrome b5 and participates in fatty acid synthesis, cholesterol synthesis, and xenobiotic oxidation as a member of the electron transport chain on the endoplasmic reticulum. In erythrocytes, the enzyme also participates in the reduction of methemoglobin
physiological function
-
cytochrome b5 reductase 3 expression and activity is critical for nitric oxide-stimulated cGMP production and vasodilation
physiological function
-
enzyme overexpression extends lifespan, survival and improves lipid metabolism in Drosophila melanogaster
physiological function
-
enzyme overexpression makes cells more resistant to H2O2 (oxidative stress), 2-deoxyglucose (metabolic stress), rotenone and antimycin A (energetic stress), and lactacystin (proteotoxic stress), but does not protect cells against H2O2 and serum withdrawal. Overexpression of the enzyme induces higher mitochondrial functions such as ATP production rate, oxygen consumption rate, and activities of complexes I and II, without formation of further reactive oxygen species, consistent with lower levels of oxidative/nitrative damage and resistance to apoptotic cell death
physiological function
NADH-cytochrome b5 reductase 3 promotes colonization and metastasis formation in estrogen receptor-negative breast cancer
physiological function
-
NADH-cytochrome-b5 reductase 3 is the principal reductase involved in the mitochondrial amidoxime reducing component enzyme system and is an essential component of N reductive metabolism in human cells
physiological function
the enzyme regulates nitric oxide diffusion in the artery wall
physiological function
-
the enzyme up-regulates the expression of genes that negatively modulate angiogenesis in nasopharyngeal carcinoma cells and down-regulates the expression of vascular endothelial growth factor to reduce angiogenesis, thereby suppressing tumor formation
physiological function
-
Cb5R can use O2 as an electron acceptor using NADH as substrate. Cb5R uses one NADH molecule to reduce two O2 molecules, leading to production of superoxide anion radicals
physiological function
-
Cb5R can use O2 as an electron acceptor using NADH as substrate. Cb5R uses one NADH molecule to reduce two O2 molecules, leading to production of superoxide anion radicals. Cytochrome c binds to purified Cb5R isoforms with dissociation constants similar to the Km values for the cytochrome c-stimulated superoxide anion radical production by Cb5R isoforms and close to the Km value obtained for the NADH-dependent production of superoxide anion radicals by synaptic plasma membrane vesicles
additional information
the NADH-cytochrome b5 reductase is a flavoprotein consisting of NADH and FAD binding domains, that catalyzes electron transfer from the two-electron carrier NADH to the one-electron carrier cytochrome b5
additional information
-
the NADH-cytochrome b5 reductase is a flavoprotein consisting of NADH and FAD binding domains, that catalyzes electron transfer from the two-electron carrier NADH to the one-electron carrier cytochrome b5
additional information
-
the soluble CyB5R diffraction map reveals two distinct domains: the N-terminal FAD binding domain (from I34 to R143), which contains a binding site for the FAD prosthetic group, and the NADH domain (residues K173 to F301). These domains are separated by a large interdomain cleft (G144-V172) known as a hinge region. The three anti-parallel beta-sheets in the hinge region keep the two lobes in close proximity with the correct conformational orientation. This orientation appears to be critical for electron transfer from NADH to FAD. The FAD domain consists of six anti-parallel beta-sheets and one alpha-helix with the order 5beta/1alpha/1beta. The NADH domain forms a alpha/beta/aalpha structure consisting of five beta-strands and four alpha-helices
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
200000
-
oligomeric aggregate of detergent-solubilized enzyme in aqueous media, gel filtration
25000
-
liver, cytosol, gel filtration, sucrose density gradient centrifugation
27000
28000
30000
31000
31365
-
x * 31365, mass spectrometry of histidine-tagged variant of the soluble, catalytic diaphorase domain, comprising residues I33 to F300
32000
33000
33100
34000
34700
-
erythrocytes, cytosol, gel filtration, calculation from FAD content
35000
36000
365000
42800
-
x * 42800, chimeric protein NADH-cytochrome b5 reductase-cytochrome b5, confirmed by SDS-PAGE
44000
31000
-
x * 31000, may occur from protease cleavage of the 33000 Da protein during purification
32000
-
x * 32000, enzyme from erythrocyte cytosol and liver microsomal enzyme solubilized with cathepsin D, SDS-PAGE
32000
-
x * 32000, enzyme from liver microsomes solubilized with Triton X-100, SDS-PAGE
33000
-
x * 33000, SDS-PAGE, gel filtration in the presence of 6 M guanidine hydrochloride, gel filtration in the presence of 0.5% sodium deoxycholate
365000
-
oligomeric aggregates of detergent solubilized enzyme, sedimentation equilibrium
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
additional information
?
-
x * 31365, mass spectrometry of histidine-tagged variant of the soluble, catalytic diaphorase domain, comprising residues I33 to F300
?
-
x * 32000, enzyme from erythrocyte cytosol and liver microsomal enzyme solubilized with cathepsin D, SDS-PAGE
?
-
x * 32000, enzyme from liver microsomes solubilized with Triton X-100, SDS-PAGE
?
-
x * 31000, may occur from protease cleavage of the 33000 Da protein during purification
?
-
x * 33000, SDS-PAGE, gel filtration in the presence of 6 M guanidine hydrochloride, gel filtration in the presence of 0.5% sodium deoxycholate
?
-
x * 42800, chimeric protein NADH-cytochrome b5 reductase-cytochrome b5, confirmed by SDS-PAGE
additional information
-
liver: membrane binding domain located at NH2-terminal site of protein, 6400-6500 Da
additional information
-
liver: hydrophobic domain of approx. 30 amino acids located at COOH-terminal site of protein
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
lipoprotein
lipoprotein
-
amphipathic membrane protein containing a hydrophilic, catalytic domain and a smaller hydrohobic membrane-binding domain
lipoprotein
-
N-myristoylation is required for correct targeting to mitochondria. Part of the protein is targeted to the endoplasmic reticulum without myristoylation, which interferes with interaction of the nascent chain with signal recognition particle, while a portion is myristoylated and targeted to mitochondria
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting drop vapor diffusion method, using 2 M (NH4)2SO4, 100 mM sodium/potassium phosphate, pH 6.2, 200 mM Li2SO4, at 4°C
structure of a construct comprising the naturally fused CHORD-Sgt1 and b5R domains with bound FAD and NAD+ or NADP+. The linker between the CHORD-Sgt1 and b5R cores is more ordered than predicted, with much of it extending the beta-sandwich motif of the CHORD-Sgt1 domain. This limits the flexibility between the two domains
vapor equilibrium method, 3.6% protein solution, 30% polyethyleneglycol 4000, preliminary X-ray data
-
sitting drop method, complete data set collected for the D239T mutant enzyme
sitting drop method, reservoir: 8% poly ethylene glycol 6000, 5% 2-methyl-2,4-pentanediol in 100 mM 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid, pH 7.5, X-ray structure, resolution: enzyme 2.0 A, enzyme-NAD+ complex, 2.3 A
fully reduced form and the oxidized form of the purified liver enzyme, X-ray diffraction structure determination and analysis at 1.68 A resolution
hanging drop vapor diffusion method, using 9-12% (w/v) PEG 4,000, 100 mM potassium phosphate (pH 7.7) and 5 mM dithiothreitol
vapor diffusion method, 5 mg/ml protein, 12.5% polyethylenglycol 4000, 50 mM potassium phosphate pH 6.0-8.0, 0.1 mM EDTA, preliminary X-ray data
-
structure of the cytochrome b5 reductase domain. The N-terminal FAD-binding domain primarily consists of six antiparallel beta-strands, a C-terminal NADH-binding domain forming a Rossmann fold, and a three beta-stranded linker region connecting these two domains. The FAD cofactor is located in the cleft between the two domains and interacts primarily with the FAD-binding domain
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A178T
-
natural mutation found in patient with type I recessive congenital methaemoglobinaemia, 16.6% of wild-type enzyme activity
A179T
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
A179V
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
C204R
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
C204Y
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
D239G
-
natural mutation found in patient with type I recessive congenital methaemoglobinaemia, mutation of NADH-binding lobe. Mutant shows decreased specificity for NADH and increased specificity for NADPH, 28.5% of wild-type enzyme activity
D239T
-
the mutation changes the enzme preference for NADH to one for NADPH. Diseases related to CyB5R dysfunctions due to mutations in the gene encoding the enzyme, detailed overview
D240G
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
E213K
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
E255-
-
natural mutation found in patient with type I recessive congenital methaemoglobinaemia, mutation of NADH-binding lobe. Mutant retains stoichiometric levels FAD comparable to wild-type
F157C
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
G143D
mutation in the NADH-cytochrome b5 reductase gene in an Indian patient with type I recessive hereditary methemoglobinemia
G144D
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
G291D
-
natural mutation found in patient with type I recessive congenital methaemoglobinaemia, mutation of NADH-binding lobe. Mutant retains stoichiometric levels FAD comparable to wild-type and 35.2% of wild-type enzyme activity
G292D
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
G72A
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
G75S
-
natural mutation isolated in patient with recessive congenital methemoglobinaemia. Mutant retains stoichiometric levels of FAD, but shows decreased catalytic efficiency and reduced protein stability
G75S/V252M
-
natural mutation isolated in patient with recessive congenital methemoglobinaemia. Mutant retains stoichiometric levels of FAD, but shows decreased catalytic efficiency and reduced protein stability
G76S
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
I216T
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
I85S
L149P
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
L217P
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
L218P
-
the mutation is associated with type I recessive congenital methemoglobinemia
L239R
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
L73P
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
M127V
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
P145L
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
P145S
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
P275L
natural mutant from a patient with recessive congenital methemoglobinemia. Significant decrease in the affinity toward the physiological reducing substrate, NADH, without affecting the activity
P276L
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
P65L
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
P96H
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
R159-/D239G
-
natural mutation found in patient with type I recessive congenital methaemoglobinaemia, 40.8% of wild-type enzyme activity
R241G
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
R259W
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
R46W
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
R50Q
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
R58Q
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
S128P
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
S54R
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
V106M
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
V252M
-
natural mutation isolated in patient with recessive congenital methemoglobinaemia. Mutant retains stoichiometric levels of FAD, but shows decreased catalytic efficiency and reduced protein stability
V253M
G179A
mutant preceeding the 180GxGxxP185 motif bindin the adenosine moiety of NAD(P)H. Incorporation of FAD and adsortion and CD spectra similar to wild-type. Decrease in NADH:ferricyanide activity and affinity for NADH
G179P
mutant preceeding the 180GxGxxP185 motif bindin the adenosine moiety of NAD(P)H. Incorporation of FAD and adsortion and CD spectra similar to wild-type. Decrease in NADH:ferricyanide activity and affinity for NADH
G179T
mutant preceeding the 180GxGxxP185 motif bindin the adenosine moiety of NAD(P)H. Incorporation of FAD and adsortion and CD spectra similar to wild-type. Decrease in NADH:ferricyanide activity and affinity for NADH
G179V
mutant preceeding the 180GxGxxP185 motif bindin the adenosine moiety of NAD(P)H. Incorporation of FAD and adsortion and CD spectra similar to wild-type. Decrease in NADH:ferricyanide activity and affinity for NADH
L148P
31% of wild type activity, reduced temperature stability and resistance against limited proteolysis with trypsin, increased affinity for NAD+
P144L
28% of wild type activity, reduced temperature stability and resistance against limited proteolysis with trypsin, increased affinity for NAD+
P144L/L148P
8% of wild type activity, reduced temperature stability and resistance against limited proteolysis with trypsin, increased affinity for NAD+
P92A
mutation preceeding the conserved motif RxYTSxxSN, FAD is bound in 1:1 cofactor:protein stoichiometry
P92G
mutation preceeding the conserved motif RxYTSxxSN, FAD is bound in 1:1 cofactor:protein stoichiometry
P92S
mutation preceeding the conserved motif RxYTSxxSN, FAD is bound in 1:1 cofactor:protein stoichiometry
S127P
-
caused methemoglobinemia type II, FAD is displaced from its binding site by NADH, Km for NADH is strongly increased
Y93A
mutation preceeding the conserved motif RxYTSxxSN, FAD is bound in 1:1 cofactor:protein stoichiometry
Y93D
mutation preceeding the conserved motif RxYTSxxSN, FAD is bound in 1:1 cofactor:protein stoichiometry
Y93F
mutation preceeding the conserved motif RxYTSxxSN, FAD is bound in 1:1 cofactor:protein stoichiometry
Y93H
mutation preceeding the conserved motif RxYTSxxSN, FAD is bound in 1:1 cofactor:protein stoichiometry
Y93S
mutation preceeding the conserved motif RxYTSxxSN, FAD is bound in 1:1 cofactor:protein stoichiometry
Y93W
mutation preceeding the conserved motif RxYTSxxSN, FAD is bound in 1:1 cofactor:protein stoichiometry
P247A
P247L
P248A
P248L
P249A
P249L
T66A
Km for NADH is not affected, Km for cytochrome b5 is significantly enhanced
T66V
turnover is reduced to 10% of the native enzyme, Km for NADH is not affected, Km for cytochrome b5 is significantly enhanced
additional information
I85S
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
V253M
-
naturally occuring mutation causing the RCM phenotype depending on homozygosity/heterozygosity or other additional mutations
P247A
-
the mutant shows increased Km and decreased kcat values for NADH and cytochrome b5, as well as increased Km and kcat values for ferricyanide compared to the wild type enzyme
P247L
-
the mutation significantly decreases kcat with slight increase (about 2fold) in Km for the physiological electron donor NADH. However, Km and kcat values for the electron acceptors (both cytochrome b5 and ferricyanide) are decreased significantly
P248A
-
the mutant shows increased Km and decreased kcat values for NADH and cytochrome b5, as well as increased Km and kcat values for ferricyanide compared to the wild type enzyme
P248L
-
the mutant shows increased Km and decreased kcat values for NADH and ferricyanide compared to the wild type enzyme
P249A
-
the mutation affects the Km (NADH) values to increase slightly by a factor of 3 compared to the wild type enzyme
P249L
-
the mutant shows increased Km and kcat values for NADH, ferricyanide and cytochrome b5 compared to the wild type enzyme
additional information
-
three T-DNA insertional knockout mutants of the gene CBR1 encoding cytochrome b5 reductase showing distorted segregation, with greatly reduced penetrance through the male gametophyte. In fertilization experiments, pollen of cbr1-2 plants germinated on wild-type and cbr1-2 stigmas, but the majority of pollen tubes stopped growing prior to reaching the ovules, leading to severely reduced fertilization and seed set
additional information
-
expression of histidine-tagged variant of the soluble, catalytic diaphorase domain, comprising residues I33 to F300. Fragment retains both NADH:ferricyanide reductase and NADH:cytochrome b5 reductase activities
additional information
naturally occurring mutations of CYB5R3 detected in patients with recessive congenital methaemoglobinaemia
additional information
-
naturally occurring mutations of CYB5R3 detected in patients with recessive congenital methaemoglobinaemia
additional information
-
a chimeric protein NADH-cytochrome b5 reductase-cytochrome b5 is constructed
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
51
-
denaturation temperature. The difference in the hydrophobic interactions in the Physarum polycephalum and human cyt b5R proteins is the primary factor underlying the lower denaturation temperature of Physarum polycephalum cyt b5R
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
application of HPLC during purification causes inactivation
enzyme from erythrocyte loses its activity in the absence of EDTA after 5 d at 4°C
-
hydrophilic domain is unfolded at approx. 1 M guanidinium hydrochloride whereas much higher concentrations are required for denaturation of the hydrophobic domain
-
inactivation caused by solubilization with detergents, activity restored by phosphatidylcholine
-
unstable, 40% loss of activity at 0°C overnight, 1 mg/ml gelatin stabilizes, FAD protects against inactivation
-
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OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 25 mM phosphate buffer, pH 7.6, 1 mM EDTA, 0.1 mM dithiothreitol, at least a few months
-
4°C, phosphate buffered saline, pH 7.4, protein concentration 2-3 mg/ml, stable for 3 weeks
-
frozen, 50 mM potassium phosphate buffer, pH 7.5, 1 mM EDTA, several weeks
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate precipitation, DE-52 cellulose column chromatography, hydroxylapatite column chromatography, and NAD+-agarose column chromatography
-
ammonium sulfate precipitation, DEAE-Sepharose CL-6B column chromatography, 5'-ADP-agarose (or 5'-AMP-agarose) gel column chromatography, and Ni-NTA-agarose column chromatography
-
DEAE-cellulose column chromatography, DEAE-Sepharose column chromatography, DEAE-Trisacryl column chromatography, agarose-hexane-NAD column chromatography, ADP-agarose column chromatography, 5'-AMP-Sepharose column chromatography, blue-Ultrogel column chromatography, octylamino-Sepharose column chromatography, blue 2-Sepharose column chromatography, Sephadex G-100 gel filtration, 5'-ADP-hexane-agarose column chromatography, hydroxyapatite column chromatography, CM-Sephadex gel filtration, or NAD agarose column chromatography
DEAE-cellulose column chromatography, Toyopearl butyl column chromatography, and Sephacryl S200 gel filtration
-
DEAE-trisacryl, Blue ultrogel, Mono Q
lysosome-solubilization
native enzyme from liver by anion-exchange chromatography of the detergent solubilized microsomes on two successive DEAE-cellulose columns and an affinity chromatography on adenosine 5'-diphosphate-agarose, to homogeneity
-
native enzyme from liver microsomes by anion exchange chromatography and affinity chromatography
-
native membrane-bound isozyme by solubiization from membranes, anion exchange chromatography, and affinity chromatography
-
Ni2+-NTA bead chromatography, HiTrap Q column chromatography, HiTrap phenyl column chromatography, and Superdex 200 gel filtration
polyethylene glycol precipitation, DEAE-cellulose, hydroxylapatite, ADP-agarose
-
recombinant enzyme
recombinant wild-type, K97A, K97R, S99A, S99T, S99V, R63A, R63Q, R63K, Y65A and Y65F mutant enzymes
-
DEAE-cellulose column chromatography, DEAE-Sepharose column chromatography, DEAE-Trisacryl column chromatography, agarose-hexane-NAD column chromatography, ADP-agarose column chromatography, 5'-AMP-Sepharose column chromatography, blue-Ultrogel column chromatography, octylamino-Sepharose column chromatography, blue 2-Sepharose column chromatography, Sephadex G-100 gel filtration, 5'-ADP-hexane-agarose column chromatography, hydroxyapatite column chromatography, CM-Sephadex gel filtration, or NAD agarose column chromatography
-
DEAE-cellulose column chromatography, DEAE-Sepharose column chromatography, DEAE-Trisacryl column chromatography, agarose-hexane-NAD column chromatography, ADP-agarose column chromatography, 5'-AMP-Sepharose column chromatography, blue-Ultrogel column chromatography, octylamino-Sepharose column chromatography, blue 2-Sepharose column chromatography, Sephadex G-100 gel filtration, 5'-ADP-hexane-agarose column chromatography, hydroxyapatite column chromatography, CM-Sephadex gel filtration, or NAD agarose column chromatography
DEAE-cellulose column chromatography, DEAE-Sepharose column chromatography, DEAE-Trisacryl column chromatography, agarose-hexane-NAD column chromatography, ADP-agarose column chromatography, 5'-AMP-Sepharose column chromatography, blue-Ultrogel column chromatography, octylamino-Sepharose column chromatography, blue 2-Sepharose column chromatography, Sephadex G-100 gel filtration, 5'-ADP-hexane-agarose column chromatography, hydroxyapatite column chromatography, CM-Sephadex gel filtration, or NAD agarose column chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme coexpressed together with cytochrome b5 and CYP2E1or with CYP2E1 but without cytochrome b5 in Salmonella typhimurium strain 7108
-
expressed in Escherichia coli BL21(DE3) cells
expression in Escherichia coli
expression of a soluble fusion protein comprising a b-type cytochrome containing domain and a FAD-containing domain
-
expression of wild-type, H49A, H49E, H49K, H49Y, and DELTAF272 mutant enzymes in Escherichia coli
-
expression of wild-type, K110A, K110M and K110R mutant enzymes in Escherichia coli
-
expression of wild-type, K110R, K110H, K110A, K110E and K110Q mutant enzymes in Escherichia coli
expression of wild-type, K97A, K97R, S99A, S99T, S99V, R63A, R63Q, R63K, Y65A and Y65F mutant enzymes in Escherichia coli
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heterologous expression in Escherichia coli or in yeast cells via different expression vectors, in Aspergillus oryzae using pNGA142, Salmonella typhimurium using pIN, in Spodoptera frugiperda Sf9 insect cells using pFASTBAC baculovirus vectors, in cell-free systems, in plant cells using pRT, in lymphoid cells using Epstein-Barr virus, and in CHO cells using SV40 transfection method
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mutant enzymes expressed in Escherichia coli BL21(DE3)-RIL as His-tag fusion proteins
wild type and mutant enzyme expressed in Escherichia coli BL21-CodonPlus (DE3)-RIL
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
a significant increase in the activity of cytochrome b5 reductase is observed after trichloroaceticacid treatment at 0.2% (w/v) (about 12 mM) concentration in drinking water ad libitum for 60 days as compared to control groups
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enzyme transcript levels are decreased in nasopharyngeal carcinoma cell lines and tumor biopsies
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
drug development
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flavonoids, regarding b5 reductase inhibition, indicate a potential for significant flavonoiddrug and/or flavonoidxenobiotic interactions which may have important therapeutic and toxicological outcomes for certain drugs and/or xenobiotics.
medicine
analysis
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detailed analysis of biphasic rate of reduction of cytochrome b5 in membranes with evaluation of data in terms of two-dimensional random walk model. The initial rapid phase is completed within 10 msec and over 90% of cytochrome b5 are reduced in 40 msec
analysis
microplate method based on a standard 96-well microplate format to simplify the quantification of NADH-CYB5R activity. Enzyme activity in 25 diagnosed cases of recessive congenital methemoglobinemia ranges from 6.09 to 10.07 IU/g Hb whereas normal control ranges from 13.42 to 21.58 IU/g Hb. Hemolysate samples have significant loss of activity when stored at 4°C and retain stable activity at -20°C for 1 week
medicine
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potentially an important enzyme required for the reductive activation of bioreductive drugs that can be used in the treatment of solid tumours
medicine
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enzyme and cytochrome b5 play a direct role in metabolic activation of antimicrobial prodrug DB289 to furamidine
medicine
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isolation of mutations leading to type I recessive congenital methaemoglobinaemia
medicine
natural mutant P275L from a patient with recessive congenital methemoglobinemia shows significant decrease in the affinity toward the physiological reducing substrate, NADH, without affecting the activity
medicine
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reduction of arylhydroxylamine carcinogens by enzyme and ferricytochrome b5 as a source of individual variability with respect to cancer susceptibility following exposure to arylhydroxylamines
medicine
to establish a diagnosis of recessive congenital methaemoglobinaemia (RCM), it is important to demonstrate enzyme deficiency of cb5r and this is usually done using a spectrophotometric method,. RCM type I patients manifest a deficiency of cb5r in erythrocytes only whereas type II patients harbour the deficiency in both erythrocytes and leucocytes
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EXTERNAL LINKS (specific for EC-Number 1.6.2.2)
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Release 2023.1 (January 2023)
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