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Information on EC 1.2.3.1 - aldehyde oxidase and Organism(s) Homo sapiens
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1.2.3.1 aldehyde oxidaseIUBMB Comments
Contains molybdenum, [2Fe-2S] centres and FAD. The enzyme from liver exhibits a broad substrate specificity, and is involved in the metabolism of xenobiotics, including the oxidation of N-heterocycles and aldehydes and the reduction of N-oxides, nitrosamines, hydroxamic acids, azo dyes, nitropolycyclic aromatic hydrocarbons, and sulfoxides [4,6].
The enzyme is also responsible for the oxidation of retinal, an activity that was initially attributed to a distinct enzyme (EC 1.2.3.11, retinal oxidase) [5,7].
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Word Map
- 1.2.3.1
- xanthine
- molybdenum
- allopurinol
- oxidases
- menadione
- benzaldehyde
-
abscisic
- n-oxide
-
n-heterocyclic
- moco
- phthalazine
- raloxifene
-
molybdenum-containing
-
xanthinuria
- hydralazine
-
oxidase-mediated
-
drug-drug
-
molybdoenzymes
- sulphite
- o6-benzylguanine
- molybdopterin
-
flavin-containing
- disulfiram
- n1-methylnicotinamide
- oxypurinol
- nutrition
- medicine
-
hypouricemia
-
amidoxime
-
oxidase-catalyzed
- pharmacology
- synthesis
- degradation
- cyp2a6
-
nitroreduction
- imidacloprid
-
neonicotinoids
- phenanthridine
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
aldehyde oxidase, aldehyde oxidase 1, retinal oxidase, formate oxidase, maox3, atraaox2, aldehyde oxidase 3, aldehyde oxidase 2, aldehyde:oxygen oxidoreductase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aldehyde oxidase 1
AOX1
quinoline oxidase
-
-
-
-
Retinal oxidase
-
-
-
-
retinene oxidase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
aldehyde:oxygen oxidoreductase
Contains molybdenum, [2Fe-2S] centres and FAD. The enzyme from liver exhibits a broad substrate specificity, and is involved in the metabolism of xenobiotics, including the oxidation of N-heterocycles and aldehydes and the reduction of N-oxides, nitrosamines, hydroxamic acids, azo dyes, nitropolycyclic aromatic hydrocarbons, and sulfoxides [4,6].
The enzyme is also responsible for the oxidation of retinal, an activity that was initially attributed to a distinct enzyme (EC 1.2.3.11, retinal oxidase) [5,7].
CAS REGISTRY NUMBER
COMMENTARY
9029-07-6
-
9033-52-7
-
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
(+/-)-4-(4-cyanoanilino)-5,6-dihydro-7-hydroxy-7H-cyclopenta-[d]-pyrimidine + H2O + O2
?
-
i.e. RS-8359
-
-
?
2-fluoro-N-methyl-4-[7-(6-quinolinylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide + H2O + O2
?
-
i.e. c-met inhibitor capmatinib
-
-
?
2-[(6-[[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl)amino]ethan-1-ol + H2O + O2
? + H2O2
-
-
-
-
?
5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine + H2O + O2
?
-
i.e. brimonidine
-
-
?
5-nitroquinoline + H2O + O2
2-oxo-5-nitroquinoline + 5-aminoquinoline + 2-oxo-5-aminoquinoline
-
-
-
?
6-chloroquinazolin-4(3H)-one + H2O + O2
6-chloroquinazoline-2,4(1H,3H)-dione + H2O2
-
-
-
-
?
6-methoxyquinazolin-4(3H)-one + H2O + O2
6-methoxyquinazoline-2,4(1H,3H)-dione + H2O2
-
-
-
-
?
6-methylquinazolin-4(3H)-one + H2O + O2
6-methylquinazoline-2,4(1H,3H)-dione + H2O2
-
-
-
-
?
6-[[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-N-(oxetan-3-yl)quinolin-3-amine + H2O + O2
? + H2O2
-
-
-
-
?
6-[[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-N-(oxolan-3-yl)quinolin-3-amine + H2O + O2
? + H2O2
-
-
-
-
?
6-[[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-N-[(oxolan-3-yl)methyl]quinolin-3-amine + H2O + O2
? + H2O2
-
-
-
-
?
6-[[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinoline + H2O + O2
? + H2O2
-
-
-
-
?
BIBX1382 + H2O + O2
BIBU1476 + ?
-
high hepatic clearance of 17 to 18 ml/(min * kg)
product identification by high-resolution mass spectrometry
-
?
carbazeran + H2O + O2
carbazeran phthalazinone + ?
-
high hepatic clearance of 17 to 18 ml/(min * kg)
product identification by high-resolution mass spectrometry
-
?
imidacloprid + H2O + O2 + N-methylnicotinamide
nitroso-imidacloprid + amino-imidacloprid + H2O2 + ?
-
-
in presence of N-methylnicotinamide, ratio of amino- to nitroso-products is 26 to 50
-
?
N-(2-(dimethylamino)ethyl)acridine-4-carboxamide + H2O + O2
N-[(2-dimethylamino)ethyl] acridine-4-carboxamide-9(10H)-acridone + H2O2
-
-
-
?
N-[(2-dimethylamino)ethyl] acridine-4-carboxamide + H2O + O2
N-[(2-dimethylamino)ethyl] acridine-4-carboxamide-9(10H)-acridone + H2O2
-
-
-
-
?
N-[(2-dimethylamino)ethyl]acridine-4-carboxamide + H2O + O2
DACA-9(10H)-acridone + H2O2
-
N-[(2-dimethylamino)ethyl]acridine-4-carboxamide i.e. DACA, an experimental antitumor agent
-
-
?
N-[2-(dimethylamino)ethyl]acridine-4-carboxamide + H2O + O2
N-[(2-dimethylamino)ethyl] acridine-4-carboxamide-9(10H)-acridone + H2O2
-
-
-
?
N1-methylnicotinamide + H2O + O2
N1-methyl-2-pyridone-5-carboxamide + N1-methyl-4-pyridone-3-carboxamide + H2O2
-
-
-
-
?
XK-469 + H2O + O2
3-oxo-XK-469 + ?
-
hepatic clearance less than 4.3 ml/(min * kg)
product identification by high-resolution mass spectrometry
-
?
zaleplon + H2O + O2
5-oxozaleplon + ?
-
hepatic clearance less than 4.3 ml/(min * kg)
product identification by high-resolution mass spectrometry
-
?
zebularine + H2O + O2
uridine + H2O2
-
-
major catabolic route for oral antitumor agent zebularine
-
?
zoniporide + H2O + O2
2-oxozoniporide + H2O2
-
i.e. 1-(quinolin-5-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl guanidine
-
-
?
O6-benzylguanine + H2O + O2
O6-benzyl-8-oxoguanine + ?
-
hepatic clearance of 11.2 to 12.8 ml/(min * kg)
product identification by high-resolution mass spectrometry
-
?
additional information
?
-
-
enzyme plays an important role in the biotransformation of drugs and xenobiotics, e.g. antiviral, antimalarial and antitumour compounds and nicotine
-
-
?
additional information
?
-
-
hepatic clearance for substrates of aldehyde oxidase i.e. BIBX1382, carbazeran, O6-benzylguanine, zaleplon, and XK-469 is investigated using cryopreserved hepatocytes
confirmation of aldehyde oxidase mediated metabolism via incubations in the presence of water containing the 18-O isotope and corresponding isotope patterns in mass spectra
-
?
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
additional information
?
-
-
enzyme plays an important role in the biotransformation of drugs and xenobiotics, e.g. antiviral, antimalarial and antitumour compounds and nicotine
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
molybdenum cofactor
during the displacement of the products away from the Moco, the transfer of electrons from the catalytic site to the FAD site is proton-coupled. The most favorable and fastest pathway for the enzyme to complete its catalytic cycle is that with MoV and a deprotonated SH ligand of the Moco with the FAD molecule converted to its semiquinone form, FADH radical
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
allopurinol
does not affect the extent of the oxidation reactions of 5-nitroquinoline but instead increases the amount of reductive metabolite produced by around 60%
fenofibrate
-
in mature adipocytes, enzyme expression is reduced in presence of 50 microM fenofibrate
palmitic acid
-
enzyme expression is reduced in 3T3-L1 cells differentiated in presence of 400 microM palmitic acid
siRNA
knock-down of AOX1 in HepG2 cells, significantly reduces ABCA1-dependent lipid efflux and enhances phagocytic uptake of microspheres similar to ABCA1 deficiency, without affecting ABCA1 mRNA and protein levels
-
additional information
-
addition of 100 microM allopurinol has no significant effect on enzyme activity
-
hydralazine
-
upon coincubation of BIBX1382, carbazeran, and O6-benzylguanine with 50 microM hydralazine, metabolic clearance is substantially attenuated
quetiapine
-
additionally shows inhibition towards the major CYP450 enzymes tested
raloxifene
-
specific inhibitor of aldehyde oxidase, complete inhibition at 0.01 mM
raloxifene
-
additionally acts as non-specific inhibitor of all major tested CYP450 enzymes
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
aldehyde oxidase activity rapidly increases with age up to about one year after birth
-
additional information
-
significant correlations between aldehyde oxidase activity and various growth indices like age, body weight, body surface area, and liver volume. Aldehyde oxidase activity rapidly increases with increase of age up to about 1 year. No differences in sex, but individual variation of developmental changes in aldehyde oxidase activity among monozygotic twins
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0026
2-[(6-[[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl)amino]ethan-1-ol
-
liver cytosol, pH not specified in the publication, temperature not specified in the publication
-
0.022
6-[[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-N-(oxetan-3-yl)quinolin-3-amine
-
liver cytosol, pH not specified in the publication, temperature not specified in the publication
-
0.0086
6-[[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-N-(oxolan-3-yl)quinolin-3-amine
-
liver cytosol, pH not specified in the publication, temperature not specified in the publication
-
0.063
6-[[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-N-[(oxolan-3-yl)methyl]quinolin-3-amine
-
liver cytosol, pH not specified in the publication, temperature not specified in the publication
-
0.084
6-[[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinoline
-
liver cytosol, pH not specified in the publication, temperature not specified in the publication
-
0.0034
zoniporide
-
in 25 mM phosphate buffer at 37°C, pH not specified in the publication
0.1
5-nitroquinoline
metabolite 5-aminoquinoline, presence of N-(2-(dimethylamino)ethyl)acridine-4-carboxamide, pH 7.4, 37°C
-
0.912
5-nitroquinoline
metabolite 2-oxo-5-nitroquinoline, presence of N-(2-(dimethylamino)ethyl)acridine-4-carboxamide, pH 7.4, 37°C
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.18
5-nitroquinoline
metabolite 5-aminoquinoline, presence of N-(2-(dimethylamino)ethyl)acridine-4-carboxamide, pH 7.4, 37°C
-
1.31
5-nitroquinoline
metabolite 2-oxo-5-nitroquinoline, presence of N-(2-(dimethylamino)ethyl)acridine-4-carboxamide, pH 7.4, 37°C
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.17
5-nitroquinoline
metabolite 5-aminoquinoline, presence of N-(2-(dimethylamino)ethyl)acridine-4-carboxamide, pH 7.4, 37°C
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00062
chlorpromazine
-
Ki-value for free enzyme with DACA as substrate, assay at 100 microM concentration, pH 7.4 and 37°C
0.0051
clozapine
-
Ki-value for free enzyme with DACA as substrate, assay at 100 microM concentration, pH 7.4 and 37°C
0.0012
domperidone
-
Ki-value for free enzyme with DACA as substrate, assay at 100 microM concentration, pH 7.4 and 37°C
0.0000023
raloxifene
-
Ki-value for free enzyme with DACA as substrate, assay at 100 microM concentration, pH 7.4 and 37°C
0.00087
beta-estradiol
-
Ki-value for free enzyme with DACA as substrate, assay at 100 microM concentration, pH 7.4 and 37°C
0.0044
beta-estradiol
-
Ki-value for enzyme-substrate complex with DACA as substrate, assay at 100 microM concentration, pH 7.4 and 37°C
0.00043
ethinyl estradiol
-
Ki-value for free enzyme with DACA as substrate, assay at 100 microM concentration, pH 7.4 and 37°C
0.0036
ethinyl estradiol
-
Ki-value for enzyme-substrate complex with DACA as substrate, assay at 100 microM concentration, pH 7.4 and 37°C
0.00047
menadione
-
Ki-value for free enzyme with DACA as substrate, assay at 100 microM concentration, pH 7.4 and 37°C
0.0015
menadione
-
Ki-value for enzyme-substrate complex with DACA as substrate, assay at 100 microM concentration, pH 7.4 and 37°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0098
menadione
Homo sapiens
-
in 25 mM phosphate buffer at 37°C, pH not specified in the publication
12
raloxifene
Homo sapiens
-
in 25 mM phosphate buffer at 37°C, pH not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
isoform AOX1 mRNA is higher in visceral compared to subcutaneous adipose tissue, Aox1 protein is detected in both fat depots
-
presence of the AOX1 transcript in the glial cell population of the spinal cord
in kidney proximal tubular epithelial cells, ABCA1 and AOX1 are coexpressed
additional information
-
-
strong AOX1 expression in normal liver, and in cirrhosis. Hepatocellular carcinomas show either a complete loss or reduced expression of AOX1
additional information
in adrenocortical cells, ABCA1 and AOX1 are coexpressed. Absent from skeletal muscle, small intestine, MCF-7, PC3, CaCo-2, and HT-29 cells
additional information
-
in adrenocortical cells, ABCA1 and AOX1 are coexpressed. Absent from skeletal muscle, small intestine, MCF-7, PC3, CaCo-2, and HT-29 cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
physiological function
metabolism
-
3-substituted quinoline triazolopyridine compounds used as c-Met kinase inhibitors are subject to aldehyde oxidase-mediated metabolism. Several compouinds are unstable in monkey liver cytosolic incubations. Small electron-donating groups at the 3-quinoline moiety make the analogs more susceptible to metabolism, whereas large 3-substituents may reverse the trend
metabolism
density functional theory using the molybdenum cofactor as a model to study structural and energetic aspects of different mechanisms. For a series of 6-substituted 4-quinazolinones, the trend in activation energies is the same for three tested reaction mechanisms. During the transition states for the formation of all possible metabolites for a series of known substrates, the lowest activation energies correspond in all cases to the experimentally observed sites of metabolism
metabolism
nitroaromatic drugs clonazepam, flunitrazepam, flutamide, nilutamide, nimesulide, and nimetazepam are substantially reduced by recombinant AOX1 and human liver cytosol, whereas azelnidipine, nifedipine, and nimodipine are slightly reduced and metronidazole and tolcapone are not reduced. Nitroaromatic drugs reduced by AOX1 possess a relatively electron-deficient nitro group
metabolism
the oxidation of phthalazine reaction involves three sequential steps: protonation of the substrate's N2 atom by Lys893, nucleophilic attack of the hydroxyl group of the molybdenum cofactor (Moco) to the substrate, and hydride transfer from the substrate to the sulfur atom of the Moco. The rate-limiting step corresponds to hydride transfer. Residue Lys893 plays a relevant role in the reaction, being important for the anchorage of the substrate close to the Moco, and also in the catalytic reaction. During the displacement of the products away from the Moco, the transfer of electrons from the catalytic site to the FAD site is proton-coupled. The most favorable and fastest pathway for the enzyme to complete its catalytic cycle is that with MoV and a deprotonated SH ligand of the Moco with the FAD molecule converted to its semiquinone form, FADH radical
physiological function
the amount of AOX1 in human liver is similar to rabbit liver, while the metabolism of methotrexate in rabbit liver cytosol is several orders of magnitude higher than any of the other species tested
physiological function
in vitro reaction of 5-nitroquinoline with AOX under aerobic conditions generates the oxidized 2-oxo-5-nitroquinoline, the reduced 5-aminoquinoline and the oxidized/reduced 2-oxo-5-aminoquinoline metabolites. In human liver cytosol, coincubation of 5-nitroquinoline and AOX oxidative substrates N-(2-(dimethylamino)ethyl)acridine-4-carboxamide and phthalazine significantly increases the yield of the reduced metabolite, while oxidized metabolites production are lowered
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). AOXA_HUMAN
1338
0
147918
Swiss-Prot
other Location (Reliability: 1)
A0A286LWX1_HUMAN
1338
0
147831
TrEMBL
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
homology modeling and docking of inhibitors epigallocatchin and epigallocatechin gallate. Interactions include pi-stacking between the phenyl rings of epigallocatchin and residues F923 and F885 and hydrogen bonding between two phenol groups and the carboxylate group on residue E882
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
I1085A
slightly higher activity on methotrexate compared to the wild type
I1085A/V1016R
significant decrease in activity compared to the wild type and I1085A mutant
I11085A/A1023Y
catalytic turnover of methotrexate is similar to the I1085A single mutant
additional information
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
additional information
-
mutation of two amino acid residues in the active site of human XOR (mutants E803V and R881M) for purine substrates results in conversion of the substrate preference to aldehyde oxidase type
additional information
-
knock-down of isoform AOX1 by siRNA impairs adipogenesis and reduces adiponectin release
additional information
substitution of nucleotides of human AOX1 with relevant ones of rabbit AOX1
additional information
-
substitution of nucleotides of human AOX1 with relevant ones of rabbit AOX1
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
nutrition
-
identification of 17 diet-derived constituents as inhibitors, with Kiss that vary approximately 300fold. Inhibitors bind within the active site and elucidate key enzyme-inhibitor interactions. QSAR modeling identified three structural descriptors that correlate with inhibition potency
medicine
-
aldehyde oxidase plays an important role in metabolizing many drugs, so aldehyde oxidase activity in individual patients may be a useful parameter for dose adjustment to avoid severe toxicity. Aldehyde oxidase activity is immature in children below 1 year of age, dose adjustment based on individual aldehyde oxidase activity shall be made for such patients
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
medicine
-
AOX1 may affect plasma HDL levels by altering ATP-binding cassette transporter A1 activity
medicine
significant correlations between reduced AOX1 expression and tumor stage, or metastatic or regional lymph node states. Reduced expression of AOX1 in malignant transformed hepatocytes supports the differentiation dependent upregulation of AOX1
medicine
-
combined computational and experimental investigation of drug-like molecules that are potential aldehyde oxidase substrates and identification of multiple sites of metabolism mediated by AOX
medicine
-
3-substituted quinoline triazolopyridine compounds used as c-Met kinase inhibitors are subject to aldehyde oxidase-mediated metabolism. Several compouinds are unstable in monkey liver cytosolic incubations. Small electron-donating groups at the 3-quinoline moiety make the analogs more susceptible to metabolism, whereas large 3-substituents may reverse the trend
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Al-Salmy, H.S.
Individual variation in hepatic aldehyde oxidase activity
IUBMB Life
51
249-253
2001
Homo sapiens
Obach, R.S.; Huynh, P.; Allen, M.C.; Beedham, C.
Human liver aldehyde oxidase: inhibition by 239 drugs
J. Clin. Pharmacol.
44
7-19
2004
Homo sapiens
Klecker, R.W.; Cysyk, R.L.; Collins, J.M.
Zebularine metabolism by aldehyde oxidase in hepatic cytosol from humans, monkeys, dogs, rats, and mice: influence of sex and inhibitors
Bioorg. Med. Chem.
14
62-66
2006
Canis lupus familiaris, Homo sapiens, Macaca fascicularis, Mus musculus, Mus musculus CD-1, Rattus norvegicus
Dick, R.A.; Kanne, D.B.; Casida, J.E.
Identification of aldehyde oxidase as the neonicotinoid nitroreductase
Chem. Res. Toxicol.
18
317-323
2005
Gallus gallus, Homo sapiens, Macaca fascicularis, Oryctolagus cuniculus, Rattus norvegicus
Yamaguchi, Y.; Matsumura, T.; Ichida, K.; Okamoto, K.; Nishino, T.
Human Xanthine oxidase changes its substrate specificity to aldehyde oxidase type upon mutation of amino acid residues in the active site: roles of active site residues in binding and activation of purine substrate
J. Biochem.
141
513-524
2007
Homo sapiens
Garattini, E.; Fratelli, M.; Terao, M.
Mammalian aldehyde oxidases: genetics, evolution and biochemistry
Cell. Mol. Life Sci.
65
1019-1048
2008
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), Monodelphis domestica, Mus musculus, Mus musculus (O54754), Mus musculus (Q5SGK3), Mus musculus (Q6V956), Mus musculus (Q8VJ15), no activity in Aspergillus nidulans, Oryctolagus cuniculus (P80456), Pan troglodytes, Pongo pygmaeus, Rattus norvegicus, Rattus norvegicus (Q5QE78), Rattus norvegicus (Q5QE79), Rattus norvegicus (Q5QE80), Rattus norvegicus (Q9Z0U5), Solanum lycopersicum (Q9FV23), Solanum lycopersicum (Q9FV24), Solanum lycopersicum (Q9FV25), Takifugu rubripes, Tetraodon nigroviridis, Xenopus laevis (Q6GMC5), Zea mays (O23887), Zea mays (O23888)
Tayama, Y.; Miyake, K.; Sugihara, K.; Kitamura, S.; Kobayashi, M.; Morita, S.; Ohta, S.; Kihira, K.
Developmental changes of aldehyde oxidase activity in young Japanese children
Clin. Pharmacol. Ther.
81
567-572
2007
Homo sapiens
Graessler, J.; Fischer, S.
The dual substrate specificity of aldehyde oxidase 1 for retinal and acetaldehyde and its role in ABCA1 mediated efflux
Horm. Metab. Res.
39
775-776
2007
Homo sapiens, Rattus norvegicus, Bos taurus (P48034), Oryctolagus cuniculus (P80456), Gallus gallus (Q2QB50)
Sigruener, A.; Buechler, C.; Orso, E.; Hartmann, A.; Wild, P.J.; Terracciano, L.; Roncalli, M.; Bornstein, S.R.; Schmitz, G.
Human aldehyde oxidase 1 interacts with ATP-binding cassette transporter-1 and modulates its activity in hepatocytes
Horm. Metab. Res.
39
781-789
2007
Homo sapiens (Q06278), Homo sapiens
Alfaro, J.F.; Joswig-Jones, C.A.; Ouyang, W.; Nichols, J.; Crouch, G.J.; Jones, J.P.
Purification and mechanism of human aldehyde oxidase (Aox1) expressed in E. coli
Drug Metab. Dispos.
37
2393-2398
2009
Homo sapiens
Weigert, J.; Neumeier, M.; Bauer, S.; Mages, W.; Schnitzbauer, A.A.; Obed, A.; Groeschl, B.; Hartmann, A.; Schaeffler, A.; Aslanidis, C.; Schoelmerich, J.; Buechler, C.
Small-interference RNA-mediated knock-down of aldehyde oxidase 1 in 3T3-L1 cells impairs adipogenesis and adiponectin release
FEBS Lett.
582
2965-2972
2008
Homo sapiens, Mus musculus
Zientek, M.; Jiang, Y.; Youdim, K.; Obach, R.S.
In vitro-in vivo correlation for intrinsic clearance for drugs metabolized by human aldehyde oxidase
Drug Metab. Dispos.
38
1322-1327
2010
Homo sapiens
Dalvie, D.; Zhang, C.; Chen, W.; Smolarek, T.; Obach, R.S.; Loi, C.M.
Cross-species comparison of the metabolism and excretion of zoniporide: contribution of aldehyde oxidase to interspecies differences
Drug Metab. Dispos.
38
641-654
2010
Homo sapiens
Hutzler, J.M.; Yang, Y.S.; Albaugh, D.; Fullenwider, C.L.; Schmenk, J.; Fisher, M.B.
Characterization of aldehyde oxidase enzyme activity in cryopreserved human hepatocytes
Drug Metab. Dispos.
40
267-275
2012
Homo sapiens
Barr, J.T.; Jones, J.P.
Evidence for substrate-dependent inhibition profiles for human liver aldehyde oxidase
Drug Metab. Dispos.
41
24-29
2013
Homo sapiens
Choughule, K.V.; Joswig-Jones, C.A.; Jones, J.P.
Interspecies differences in the metabolism of methotrexate: An insight into the active site differences between human and rabbit aldehyde oxidase
Biochem. Pharmacol.
96
288-295
2015
Oryctolagus cuniculus (O54754), Oryctolagus cuniculus, Homo sapiens (Q06278), Homo sapiens
Barr, J.T.; Jones, J.P.; Oberlies, N.H.; Paine, M.F.
Inhibition of human aldehyde oxidase activity by diet-derived constituents: structural influence, enzyme-ligand interactions, and clinical relevance
Drug Metab. Dispos.
43
34-41
2015
Homo sapiens
Xu, Y.; Li, L.; Wang, Y.; Xing, J.; Zhou, L.; Zhong, D.; Luo, X.; Jiang, H.; Chen, K.; Zheng, M.; Deng, P.; Chen, X.
Aldehyde oxidase mediated metabolism in drug-like molecules: a combined computational and experimental study
J. Med. Chem.
60
2973-2982
2017
Homo sapiens
Nirogi, R.; Kandikere, V.; Palacharla, R.C.; Bhyrapuneni, G.; Kanamarlapudi, V.B.; Ponnamaneni, R.K.; Manoharan, A.K.
Identification of a suitable and selective inhibitor towards aldehyde oxidase catalyzed reactions
Xenobiotica
44
197-204
2014
Homo sapiens
Ferreira, P.; Cerqueira, N.; Fernandes, P.; Romao, M.; Ramos, M.
Catalytic Mechanism of human aldehyde oxidase
ACS Catal.
10
9276-9286
2020
Homo sapiens (Q06278)
-
Montefiori, M.; Jorgensen, F.S.; Olsen, L.
Aldehyde oxidase reaction mechanism and prediction of site of metabolism
ACS Omega
2
4237-4244
2017
Homo sapiens (Q06278)
Ogiso, T.; Fukami, T.; Mishiro, K.; Konishi, K.; Jones, J.P.; Nakajima, M.
Substrate selectivity of human aldehyde oxidase 1 in reduction of nitroaromatic drugs
Arch. Biochem. Biophys.
659
85-92
2018
Homo sapiens (Q06278), Homo sapiens
Paragas, E.M.; Humphreys, S.C.; Min, J.; Joswig-Jones, C.A.; Jones, J.P.
The two faces of aldehyde oxidase Oxidative and reductive transformations of 5-nitroquinoline
Biochem. Pharmacol.
145
210-217
2017
Homo sapiens (Q06278), Homo sapiens
Zhang, J.W.; Xiao, W.; Gao, Z.T.; Yu, Z.T.; Zhang, J.Y.J.
Metabolism of c-Met kinase inhibitors containing quinoline by aldehyde oxidase, electron donating, and steric hindrance effect
Drug Metab. Dispos.
46
1847-1855
2018
Macaca fascicularis, Homo sapiens, Mus musculus, Rattus norvegicus
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