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Literature summary for 1.2.3.1 extracted from

  • Garattini, E.; Fratelli, M.; Terao, M.
    Mammalian aldehyde oxidases: genetics, evolution and biochemistry (2008), Cell. Mol. Life Sci., 65, 1019-1048.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
1-hydroxyphthalazine administration to female rabbits causes an increase in the specific activity of liver aldehyde oxidase Oryctolagus cuniculus
dioxin induces AOX1 in mouse hepatoma cells Mus musculus
methyl methanesulfonate causes induction of liver aldehyde oxidase Rattus norvegicus
additional information aldehyde oxidase activity rapidly increases with age up to about one year after birth Homo sapiens
additional information fatty liver disease is associated with elevated hepatic AOX1 Rattus norvegicus
N-methyl-N'-nitro-N-nitrosoguanidine causes induction of liver aldehyde oxidase Rattus norvegicus
N-methyl-N-nitrosourea causes induction of liver aldehyde oxidase Rattus norvegicus
phenethyl isothiocyanate induces AOX1 transcript through a transcriptional mechanism Mus musculus
Phthalazine administration to female rabbits causes an increase in the specific activity of liver aldehyde oxidase Oryctolagus cuniculus
testosterone significantly increases activity in castrated males and normal female mice Mus musculus

Application

Application Comment Organism
medicine aldehyde oxidases represent an important drug-metabolizing system in the cytosol of the hepatic cell. AOX1 is potentially useful in the bioactivation of pro-drugs in human liver and lung, given that the two tissues are the only ones reported to express significant amounts of this enzymatic activity. Variability in the levels of liver aldehyde oxidase in the human population Homo sapiens
additional information aldehyde oxidase is involved in the chemo-reception of pheromonal stimuli in the antennae Mamestra brassicae
additional information variations in the levels of aldehyde oxidase activity in different strains of experimental animals Mus musculus
additional information variations in the levels of aldehyde oxidase activity in different strains of experimental animals. Gender-specific regulation of AOH1 by androgens and estrogens Mus musculus
additional information variations in the levels of aldehyde oxidase activity in different strains of experimental animals. Gender-specific regulation of AOX1 and AOH1 by androgens and estrogens Mus musculus
additional information variations in the levels of aldehyde oxidase activity in different strains of experimental animals. Gender-specific regulation of AOX1 by androgens and estrogens Mus musculus
additional information variations in the levels of aldehyde oxidase activity in different strains of experimental animals. Rat strains with low aldehyde oxidase activity lack the ability to produce the catalytically active dimer and express only the monomeric form of the enzyme Rattus norvegicus

Cloned(Commentary)

Cloned (Comment) Organism
AOX1 expressed in Escherichia coli Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information AOH2 knock-out mice are viable and transmit the genetic deficit in a mendelian fashion Mus musculus
additional information missense mutations in the coding exons of AOX1, reported in the population of the Churchill County of Nevada and in the Italian population, negatively affect catalytic activity of AOX1 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
adiponectin downregulates AOX1 expression by activating peroxisome proliferator-activated receptor-alpha Rattus norvegicus
aspartate neonatal pretreatment, which reduces circulating growth hormone levels, decreases male aldehyde oxidase activity to female levels; neonatal pretreatment, which reduces circulating growth hormone levels, decreases male aldehyde oxidase activity to female levels; neonatal pretreatment, which reduces circulating growth hormone levels, decreases male aldehyde oxidase activity to female levels; neonatal pretreatment, which reduces circulating growth hormone levels, decreases male aldehyde oxidase activity to female levels; neonatal pretreatment, which reduces circulating growth hormone levels, decreases male aldehyde oxidase activity to female levels Mus musculus
beta-carboline
-
Homo sapiens
beta-carboline a far better inhibitor of mouse AOH1 than AOX1; a far better inhibitor of mouse AOH1 than AOX1 Mus musculus
chlorpromazine
-
Homo sapiens
estradiol
-
Homo sapiens
estrogen reduces liver aldehyde oxidase activity of male animals; reduces liver aldehyde oxidase activity of male animals; reduces liver aldehyde oxidase activity of male animals; reduces liver aldehyde oxidase activity of male animals; reduces liver aldehyde oxidase activity of male animals Mus musculus
ethinyl estradiol
-
Homo sapiens
glutamate neonatal pretreatment, which reduces circulating growth hormone levels, decreases male aldehyde oxidase activity to female levels; neonatal pretreatment, which reduces circulating growth hormone levels, decreases male aldehyde oxidase activity to female levels; neonatal pretreatment, which reduces circulating growth hormone levels, decreases male aldehyde oxidase activity to female levels; neonatal pretreatment, which reduces circulating growth hormone levels, decreases male aldehyde oxidase activity to female levels; neonatal pretreatment, which reduces circulating growth hormone levels, decreases male aldehyde oxidase activity to female levels Mus musculus
menadione
-
Homo sapiens
additional information activity is significantly reduced by castration of adult males. Hypophysectomy markedly decreases hepatic activity in male and to a lesser extent in female mice; activity is significantly reduced by castration of adult males. Hypophysectomy markedly decreases hepatic activity in male and to a lesser extent in female mice; activity is significantly reduced by castration of adult males. Hypophysectomy markedly decreases hepatic activity in male and to a lesser extent in female mice; activity is significantly reduced by castration of adult males. Hypophysectomy markedly decreases hepatic activity in male and to a lesser extent in female mice; activity is significantly reduced by castration of adult males. Hypophysectomy markedly decreases hepatic activity in male and to a lesser extent in female mice Mus musculus
raloxifene
-
Homo sapiens
tamoxifen
-
Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.031
-
all-trans retinaldehyde
-
Mus musculus
0.07
-
all-trans retinaldehyde
-
Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
Mus musculus 5829
-
cytosol
-
Rattus norvegicus 5829
-
cytosol
-
Oryctolagus cuniculus 5829
-

Organism

Organism UniProt Comment Textmining
Arabidopsis thaliana Q7G191
-
-
Arabidopsis thaliana Q7G192
-
-
Arabidopsis thaliana Q7G193
-
-
Bos taurus P48034
-
-
Caenorhabditis elegans O61198
-
-
Caenorhabditis elegans Q960A1
-
-
Canis lupus familiaris Q2QB47
-
-
Canis lupus familiaris Q2QB48
-
-
Danio rerio
-
-
-
Drosophila melanogaster
-
-
-
Drosophila melanogaster Q9VF53
-
-
Equus caballus
-
-
-
Gallus gallus Q2QB49
-
-
Gallus gallus Q2QB50
-
-
Homo sapiens
-
-
-
Macaca fascicularis Q5FB27
-
-
Macaca mulatta
-
-
-
Mamestra brassicae Q4VGM3 fragment
-
Monodelphis domestica
-
-
-
Mus musculus
-
DBA/2, CBA/2 C57Bl/6J and CD1 mice
-
Mus musculus O54754 DBA/2, CBA/2 C57Bl/6J and CD1 mice
-
Mus musculus Q5SGK3 DBA/2, CBA/2 C57Bl/6J and CD1 mice
-
Mus musculus Q6V956 DBA/2, CBA/2 C57Bl/6J and CD1 mice
-
Mus musculus Q8VJ15 DBA/2, CBA/2 C57Bl/6J and CD1 mice
-
no activity in Aspergillus nidulans
-
-
-
Oryctolagus cuniculus P80456
-
-
Pan troglodytes
-
-
-
Pongo pygmaeus
-
-
-
Rattus norvegicus
-
Wistar rats and Donryu rats
-
Rattus norvegicus Q5QE78 Wistar rats and Donryu rats
-
Rattus norvegicus Q5QE79 Wistar rats and Donryu rats
-
Rattus norvegicus Q5QE80 Wistar rats and Donryu rats
-
Rattus norvegicus Q9Z0U5 Wistar rats and Donryu rats
-
Solanum lycopersicum Q9FV23
-
-
Solanum lycopersicum Q9FV24
-
-
Solanum lycopersicum Q9FV25
-
-
Takifugu rubripes
-
-
-
Tetraodon nigroviridis
-
-
-
Xenopus laevis Q6GMC5
-
-
Zea mays O23887
-
-
Zea mays O23888
-
-

Purification (Commentary)

Purification (Comment) Organism
-
Homo sapiens
-
Rattus norvegicus
-
Oryctolagus cuniculus

Source Tissue

Source Tissue Comment Organism Textmining
antenna
-
Mamestra brassicae
-
brain
-
Mus musculus
-
brain AOH2 and AOH3 mRNAs are expressed in the brain at much lower levels than AOX1 and AOH1 Mus musculus
-
central nervous system
-
Mus musculus
-
central nervous system presence of the AOX1 transcript in the glial cell population of the spinal cord Homo sapiens
-
ear richest source of AOH2 mRNA in the adult mouse is the inner ear Mus musculus
-
esophagus AOH2 is also present Mus musculus
-
esophagus AOX1 mRNA is particularly abundant in the epithelial layer Mus musculus
-
eye AOH2 Mus musculus
-
head AOH2 and AOH3 Mus musculus
-
heart
-
Mus musculus
-
kidney
-
Homo sapiens
-
liver
-
Equus caballus
-
liver
-
Oryctolagus cuniculus
-
liver AOH2 is also present. Aldehyde oxidase activity shows higher levels in male than female adult mice Mus musculus
-
liver AOX1 is expressed at high levels Bos taurus
-
liver distribution of the activity is uneven, being seen mainly in the pericentral rather than the periportal area Rattus norvegicus
-
liver high amounts Homo sapiens
-
liver only trace amounts of AOX1 activity Gallus gallus
-
liver the AOH1 transcript is already detectable in newborn mice Mus musculus
-
liver the AOX1 transcript takes time to appear and is measurable only in the fully developed animal Mus musculus
-
lung
-
Rattus norvegicus
-
lung
-
Mus musculus
-
lung AOX1 is expressed at high levels Bos taurus
-
lung high amounts Homo sapiens
-
additional information AOH2 is abundant in the Harderian gland. AOH3 is restricted to the Bowman's gland Mus musculus
-
additional information completely devoid of liver aldehyde oxidase activity Canis lupus familiaris
-
neck AOH2 and AOH3 Mus musculus
-
pancreas AOH2 Mus musculus
-
respiratory system
-
Homo sapiens
-
skin AOH2 Mus musculus
-
spleen AOX1 is expressed at high levels Bos taurus
-
testis
-
Mus musculus
-
zygote very large amounts of AOH2 are predicted to be present during the early stages of development and specifically in the zygote Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(S)-RS-8359 + H2O + O2 Donryu rats show a dimorphic pattern for the 2-oxidation activity of RS-8359 Rattus norvegicus 2-keto-(S)-RS-8359 + H2O2
-
?
1-nitropyrene + H2O + O2
-
Oryctolagus cuniculus ?
-
?
6-deoxypenciclovir is catalyzed by AOX1 Homo sapiens penciclovir
-
?
6-mercaptopurine + H2O + O2
-
Homo sapiens ?
-
?
acetaldehyde + H2O + O2 is a poor substrate of AOH1 Mus musculus acetate + H2O2
-
?
acetaldehyde + H2O + O2 is a poor substrate of AOX1 Mus musculus acetate + H2O2
-
?
all-trans retinaldehyde + H2O + O2
-
Oryctolagus cuniculus all-trans retinoic acid + H2O2
-
?
all-trans retinaldehyde + H2O + O2
-
Mus musculus all-trans retinoic acid + H2O2
-
?
all-trans retinaldehyde + H2O + O2 AOH1 from the liver of CD1 mice is capable of oxidizing all-trans retinaldehyde Mus musculus all-trans retinoic acid + H2O2
-
?
all-trans retinaldehyde + H2O + O2 AOH2 from the mouse Harderian gland and AOH3 from the mouse Bowman's gland are all capable of oxidizing all-trans retinaldehyde with equal efficiency Mus musculus all-trans retinoic acid + H2O2
-
?
benzaldehyde + H2O + O2
-
Homo sapiens benzoate + H2O2
-
?
benzaldehyde + H2O + O2
-
Rattus norvegicus benzoate + H2O2
-
?
methotrexate + H2O + O2
-
Rattus norvegicus ?
-
?
additional information low and negligible quinine-oxidizing activity Rattus norvegicus ?
-
?
additional information low and negligible quinine-oxidizing activity Canis lupus familiaris ?
-
?
additional information pyridoxal is not recognized by mouse AOH2 Mus musculus ?
-
?
N1-methylnicotinamide + H2O + O2
-
Homo sapiens N1-methyl-2-pyridone-5-carboxamide + N1-methyl-4-pyridone-3-carboxamide + H2O2
-
?
N1-methylnicotinamide + H2O + O2
-
Rattus norvegicus N1-methyl-2-pyridone-5-carboxamide + N1-methyl-4-pyridone-3-carboxamide + H2O2
-
?
N1-methylnicotinamide + H2O + O2
-
Oryctolagus cuniculus N1-methyl-2-pyridone-5-carboxamide + N1-methyl-4-pyridone-3-carboxamide + H2O2
-
?
pyridoxal + H2O + O2
-
Mus musculus 4-pyridoxic acid + H2O2
-
?
quinine + H2O + O2
-
Oryctolagus cuniculus ?
-
?

Subunits

Subunits Comment Organism
dimer
-
Rattus norvegicus
monomer
-
Rattus norvegicus

Synonyms

Synonyms Comment Organism
aldehyde oxidase 1
-
Homo sapiens
aldehyde oxidase 1
-
Danio rerio
aldehyde oxidase 1
-
Monodelphis domestica
aldehyde oxidase 1
-
Gallus gallus
aldehyde oxidase 1
-
Mus musculus
aldehyde oxidase 1
-
Rattus norvegicus
aldehyde oxidase 1
-
Bos taurus
aldehyde oxidase 2
-
Gallus gallus
aldehyde oxidase 2
-
Canis lupus familiaris
aldehyde oxidase 2
-
Rattus norvegicus
aldehyde oxidase 3
-
Equus caballus
aldehyde oxidase 3
-
Canis lupus familiaris
aldehyde oxidase 3
-
Mus musculus
aldehyde oxidase 3
-
Rattus norvegicus
aldehyde oxidase 3-like 1
-
Mus musculus
aldehyde oxidase 4
-
Mus musculus
aldehyde oxidase 4
-
Rattus norvegicus
AOH
-
Gallus gallus
AOH1
-
Mus musculus
AOH1
-
Rattus norvegicus
AOH2
-
Mus musculus
AOH2
-
Macaca mulatta
AOH2
-
Canis lupus familiaris
AOH2
-
Rattus norvegicus
AOH3
-
Mus musculus
AOH3
-
Equus caballus
AOH3
-
Macaca mulatta
AOH3
-
Canis lupus familiaris
AOH3
-
Rattus norvegicus
AOX1
-
Homo sapiens
AOX1
-
Macaca mulatta
AOX1
-
Danio rerio
AOX1
-
Pan troglodytes
AOX1
-
Pongo pygmaeus
AOX1
-
Takifugu rubripes
AOX1
-
Monodelphis domestica
AOX1
-
Gallus gallus
AOX1
-
Tetraodon nigroviridis
AOX1
-
Macaca fascicularis
AOX1
-
Oryctolagus cuniculus
AOX1
-
Mus musculus
AOX1
-
Rattus norvegicus
AOX1
-
Bos taurus
AOX1
-
Xenopus laevis
AOX1
-
Drosophila melanogaster
AOX1
-
Caenorhabditis elegans
AOX1
-
Arabidopsis thaliana
AOX1
-
Solanum lycopersicum
AOX1
-
Zea mays
AOX2
-
Drosophila melanogaster
AOX2
-
Caenorhabditis elegans
AOX2
-
Arabidopsis thaliana
AOX2
-
Solanum lycopersicum
AOX2
-
Zea mays
AOX3
-
Solanum lycopersicum
AOX4
-
Drosophila melanogaster
AOX4
-
Arabidopsis thaliana

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0000029
-
-
Homo sapiens raloxifene