Disease relevance of Aox1

• In vitro, the metabolism of acetaldehyde by aldehyde oxidase caused cleavage of Lambda phage DNA [1].

High impact information on Aox1

• The reductase activity in liver 105,000 X g supernatant fraction was ascribed to DT-diaphorase, aldehyde oxidase, and other unknown enzyme(s) from the results of cofactor requirements and inhibition experiments [2].
• The Aoh3 gene maps to mouse chromosome 1 band c1 and rat chromosome 7 in close proximity to the Aox1, Aoh1, and Aoh2 loci and has an exon/intron structure almost identical to that of the other molybdo-flavoenzyme genes in the two species [3].
• Km(app) values obtained in crude extracts of male or female rat liver and post-benzamidine-purified aldehyde oxidase differed substantially from each other but could be interconverted by chemical reduction with dithiothreitol or oxidation with 4,4'-dithiodipyridine [4].
• However, it does not contain the xanthine dehydrogenase conserved sequences thought to be involved in NAD binding and in substrate specificity, and is likely to encode an aldehyde oxidase-type activity [5].
• Mobilization of iron due to acetaldehyde metabolism by aldehyde oxidase was completely inhibited by superoxide dismutase but not by catalase suggesting that superoxide radicals mediate mobilization [6].

Biological context of Aox1

• Aldehyde oxidase (AO) and xanthine oxidase (XO) are cytosolic enzymes that have been involved in some pathological conditions and play an important role in the biotransformation of drugs and xenobiotics [7].
• The role of aldehyde oxidase in ethanol-induced hepatic lipid peroxidation in the rat [8].
• Given the high clearance of this compound in cynomolgus monkey, the low oral bioavailability is probably as a result of high first-pass elimination, specifically by aldehyde oxidase, rather than poor absorption [9].
• The Michaelis-Menten kinetics of aldehyde oxidase and its inhibition by raloxifene and BAU were highly variable between species [10].
• Pharmacokinetics of the novel, high-affinity and selective dopamine D3 receptor antagonist SB-277011 in rat, dog and monkey: in vitro/in vivo correlation and the role of aldehyde oxidase [9].

Anatomical context of Aox1

• Aldehyde oxidase was purified about 120-fold from rat liver cytosol by sequential column chromatography using diethylaminoethyl (DEAE) cellulose, Benzamidine-Sepharose 6B and gel filtration [11].
• The role of the molybdenum-containing enzymes aldehyde oxidase and xanthine oxidase in the generation of such free radicals was investigated by measuring alkane production (lipoperoxidation products) in isolated rat hepatocytes during ethanol metabolism [8].
• Rabbit liver cytosol in the presence of an electron donor of aldehyde oxidase exhibited a significant N-oxide reductase activity which is comparable to the activity of the liver microsomes supplemented with NADPH [12].
• Mitochondrial and cytosolic aldehyde oxidase varied in substrate specificity and electrophoretic mobility with two major bands in each fraction, one of which was common to cytosol and mitochondria [13].
• Immunoreactivity againt aldehyde oxidase was not found in adrenal gland, spleen, mesentery or aorta, while immunoreactivity against xanthine oxidase was not found in mesentery or aorta [14].

Associations of Aox1 with chemical compounds

• Xanthine oxidase and aldehyde oxidase: a simple procedure for the simultaneous purification from rat liver [7].
• This extract was chromatographed on an Hydroxyapatite column that completely separated AO from XO [7].
• No bioactivation of ethanol to acetaldehyde was detectable when a cosubstrate of AO such as N-methylnicotinamide was included in cytosolic incubation mixtures [15].
• In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase [11].
• These results suggest that aldehyde oxidase may play a role in the oxidation of allopurinol to oxypurinol and that of pyrazinamide to 5-hydroxypyrazinamide with xanthine dehydrogenase which can oxidize both allopurinol and pyrazinamide in vivo [11].

Other interactions of Aox1

• Iron mobilization due to the metabolism of ethanol to acetaldehyde by alcohol dehydrogenase was increased 100% by the addition of aldehyde oxidase [6].
• 5-ethynyl-2(1H)-pyrimidinone: aldehyde oxidase-activation to 5-ethynyluracil, a mechanism-based inactivator of dihydropyrimidine dehydrogenase [16].
• The second cluster of genes is the glutathione S-transferase-A3-like genes, which include aflatoxin B1 aldehyde reductase and aldehyde oxidase [17].
• Menadione (an inhibitor of aldehyde oxidase) and quercetin (an inhibitor of carbonyl reductase) did not show any effects [18].
• Sensitive and specific chromatographic assays for the measurement of flavin-containing monooxygenase (N-oxygenase and S-oxygenase activities) and aldehyde oxidase activities in rat hepatocyte primary cultures were developed [19].

Analytical, diagnostic and therapeutic context of Aox1

• AO was purified about 1000-fold at a yield of 15%, with a specific activity of 3.48 U/mg, by affinity chromatography on Benzamidine-Sepharose 6B [7].
• Aldehyde oxidase activities and concentrations of 5-hydroxyindole compounds in brain tissues returned to approximately normal values one week after treatment of iron deficient animals with iron dextran [20].
• A quite similar metabolic profile was obtained on perfusion of AO-deficient WKA/Sea rat liver [21].
• These bands were also observed in Western blotting analysis using anti-rat aldehyde oxidase [22].
• Purified aldehyde oxidase from monkey liver cytosol showed two major bands and two minor bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) [22].

References