1.6.2.2: cytochrome-b5 reductase
This is an abbreviated version!
For detailed information about cytochrome-b5 reductase, go to the full flat file.
Word Map on EC 1.6.2.2
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1.6.2.2
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erythrocyte
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methemoglobinemia
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nadph-cytochrome
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hereditary
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reductases
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cyanosis
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fad
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ferricyanide
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flavoproteins
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desaturation
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dt-diaphorase
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aniline
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amidoxime
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methb
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hemolysate
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bioreductive
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n-demethylase
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aminopyrine
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marc
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n-hydroxylated
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mixed-function
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nadh-binding
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methaemoglobin
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medicine
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oxyhemoglobin
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diagnostics
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analysis
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industry
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drug development
- 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
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mixed-function
-
nadh-binding
- methaemoglobin
- medicine
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oxyhemoglobin
- diagnostics
- analysis
- industry
- drug development
Reaction
Synonyms
b5 plusb5R, b5/b5R, B5R, cb5r, CBR, CBR1, CBR1A, CBR1B, CyB5R, CYB5R2, CYB5R3, Cyb5R4, cyt b5r, cyt b5R protein, cytochrome b5 reductase, cytochrome b5 reductase 2, cytochrome b5 reductase 3, DIA1, diaphorase I, dihydronicotinamide adenine dinucleotide-cytochrome b5 reductase, HPO-19, methemoglobin reductase, NADH cytochrome b5 oxidoreductase, NADH cytochrome B5 reductase, NADH-b5R, NADH-cytochrome b 5 reductase, NADH-cytochrome b5 reductase, NADH-cytochrome b5 reductase 3, NADH-cytochrome-b5 reductase, NADH-cytochrome-b5 reductase 3, NADH-dependent cytochrome b5 reductase, NADH-ferricyanide reductase, NADH-ferricytochrome b5 oxidoreductase, NADH-ferricytochrome reductase, NADH: ferricytochrome b5 oxidoreductase, NADH:cytochrome b5 reductase, NADH:ferricytochrome b5 oxidoreductase, Ncb5or, P34/P32, P35, reduced nicotinamide adeninedinucleotide-cytochrome b5 reductase, reductase, cytochrome b5, T05H4.4
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General Information on EC 1.6.2.2 - cytochrome-b5 reductase
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GENERAL INFORMATION 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
evolution
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CyB5R is a member of the NAD(P)H-ferredoxin reductase (FNR) enzyme superfamily, phylogenetic analysis
malfunction
metabolism
physiological function
additional information
malfunction
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congenital methemoglobinemia due to deficiency of NADH-cytochrome b5 reductase is an autosomal recessive disorder characterized by life long cyanosis
malfunction
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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
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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
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autosomal cytochrome b5 reductase gene deficiency manifests with the accumulation of oxidized Fe3+ and recessive congenital methemoglobinemia in humans
malfunction
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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
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the enzyme is required for desaturation to biosynthesize polyunsaturated fatty acids
metabolism
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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
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the quantity of methemoglobin is kept in balance by an efficient redox system within erythrocytes involving the enzyme, overview
metabolism
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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
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the enzyme participates as an alternative electron donor pathway for P450 enzymes involved in ergosterol biosynthesis
metabolism
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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
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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
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the enzyme is involved in fatty acid, sphingolipid and sterol metabolism
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metabolism
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the enzyme participates as an alternative electron donor pathway for P450 enzymes involved in ergosterol biosynthesis
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physiological function
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cytochrome b5 reductase is responsible for the reduction of methemoglobin back to hemoglobin
physiological function
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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
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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
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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
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cytochrome b5 reductase 3 expression and activity is critical for nitric oxide-stimulated cGMP production and vasodilation
physiological function
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enzyme overexpression extends lifespan, survival and improves lipid metabolism in Drosophila melanogaster
physiological function
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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
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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
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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
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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
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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
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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
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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
