Aldehyde Oxidase (aldehyde + oxidase)

Distribution by Scientific Domains


Selected Abstracts


Aldehyde oxidase is coamplified with the World's most common Culex mosquito insecticide resistance-associated esterases

INSECT MOLECULAR BIOLOGY, Issue 1 2000
J. Hemingway
Abstract The evolution and spread of insecticide resistance is an important factor in human disease prevention and crop protection. The mosquito Culex quinquefasciatus is the main vector of the disease filariasis and a member of a species complex which is a common biting nuisance worldwide. The common insecticide resistance mechanism in this species involves germline amplification of the esterases est,21 and est,21. This amplification has arisen once and rapidly spread worldwide. Less common and more variable resistance phenotypes involve coamplification of est,3 and est,1, or individual amplification of a single est,1, different alleles of the same est, and est, gene loci. Est,21 and est,21 are on the same large fragment of amplified DNA (amplicon) 2.7 kb apart. We have now shown that this amplicon contains another full-length gene immediately 5, of est,21 which codes for a molybdenum-containing hydroxylase, with highest homology to aldehyde oxidase (AO) from other organisms. The full-length putative AO gene is not present on the est,3/est,1 or est,1 amplicons, but multiple truncated 5, ends of this gene are present around the presumed est,3/est,1 amplicon breakpoint. Polymerase chain reaction (PCR) analysis of insecticide-susceptible genomic DNA demonstrated that a different allele of the putative AO gene in its non-amplified form is immediately 5, of est,. The ,AO' gene on the est,21/est,21 amplicon is expressed and resistant insects have greater AO activity. This AO activity is sensitive to inhibition by an aldehyde-containing herbicide and pesticide. This enzyme may confer a selective advantage to these insects in the presence of insecticide, as AO in mammals is believed to be important in the detoxification process of several environmental pollutants. [source]


Maternal uniparental isodisomy is responsible for serious molybdenum cofactor deficiency

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2010
HAKAN GÜMÜ
Molybdenum cofactor (MoCo) deficiency is a rare autosomal recessive inherited metabolic disorder resulting in the combined deficiency of aldehyde oxidase, xanthine dehydrogenase, and sulfite oxidase. We report a male infant with MoCo deficiency whose clinical findings consisted of microcephaly, intractable seizures soon after birth, feeding difficulties, and developmental delay. Sequencing of MOCS1, MOCS2, and GEPH genes, and single nucleotide polymorphism genotyping array analysis showed, to our knowledge, unusual inheritance of MoCo deficiency/maternal uniparental isodisomy for the first time in the literature. At 10 months of age, he now has microcephaly and developmental delay, and his seizures are controlled with phenobarbital, clonozepam, and vigabatrin therapy. [source]


Aldehyde oxidase is coamplified with the World's most common Culex mosquito insecticide resistance-associated esterases

INSECT MOLECULAR BIOLOGY, Issue 1 2000
J. Hemingway
Abstract The evolution and spread of insecticide resistance is an important factor in human disease prevention and crop protection. The mosquito Culex quinquefasciatus is the main vector of the disease filariasis and a member of a species complex which is a common biting nuisance worldwide. The common insecticide resistance mechanism in this species involves germline amplification of the esterases est,21 and est,21. This amplification has arisen once and rapidly spread worldwide. Less common and more variable resistance phenotypes involve coamplification of est,3 and est,1, or individual amplification of a single est,1, different alleles of the same est, and est, gene loci. Est,21 and est,21 are on the same large fragment of amplified DNA (amplicon) 2.7 kb apart. We have now shown that this amplicon contains another full-length gene immediately 5, of est,21 which codes for a molybdenum-containing hydroxylase, with highest homology to aldehyde oxidase (AO) from other organisms. The full-length putative AO gene is not present on the est,3/est,1 or est,1 amplicons, but multiple truncated 5, ends of this gene are present around the presumed est,3/est,1 amplicon breakpoint. Polymerase chain reaction (PCR) analysis of insecticide-susceptible genomic DNA demonstrated that a different allele of the putative AO gene in its non-amplified form is immediately 5, of est,. The ,AO' gene on the est,21/est,21 amplicon is expressed and resistant insects have greater AO activity. This AO activity is sensitive to inhibition by an aldehyde-containing herbicide and pesticide. This enzyme may confer a selective advantage to these insects in the presence of insecticide, as AO in mammals is believed to be important in the detoxification process of several environmental pollutants. [source]


Does genetic variability in aldehyde oxidase and molybdenum cofactor sulfurase predict nonresponse to allopurinol?

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010
R. L. Roberts
No abstract is available for this article. [source]


Novel pharmacogenetic markers for treatment outcome in azathioprine-treated inflammatory bowel disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009
M. A. SMITH
Summary Background, Azathioprine (AZA) pharmacogenetics are complex and much studied. Genetic polymorphism in TPMT is known to influence treatment outcome. Xanthine oxidase/dehydrogenase (XDH) and aldehyde oxidase (AO) compete with TPMT to inactivate AZA. Aim, To assess whether genetic polymorphism in AOX1, XDH and MOCOS (the product of which activates the essential cofactor for AO and XDH) is associated with AZA treatment outcome in IBD. Methods, Real-time PCR was conducted for a panel of single nucleotide polymorphism (SNPs) in AOX1, XDH and MOCOS using TaqMan SNP genotyping assays in a prospective cohort of 192 patients receiving AZA for IBD. Results, Single nucleotide polymorphism AOX1 c.3404A > G (Asn1135Ser, rs55754655) predicted lack of AZA response (P = 0.035, OR 2.54, 95%CI 1.06,6.13) and when combined with TPMT activity, this information allowed stratification of a patient's chance of AZA response, ranging from 86% in patients where both markers were favourable to 33% where they were unfavourable (P < 0.0001). We also demonstrated a weak protective effect against adverse drug reactions (ADRs) from SNPs XDH c.837C > T (P = 0.048, OR 0.23, 95% CI 0.05,1.05) and MOCOS c.2107A > C, (P = 0.058 in recessive model, OR 0.64, 95%CI 0.36,1.15), which was stronger where they coincided (P = 0.019). Conclusion, These findings have important implications for clinical practice and our understanding of AZA metabolism. [source]


Increase in BrAO1 gene expression and aldehyde oxidase activity during clubroot development in Chinese cabbage (Brassica rapa L.)

MOLECULAR PLANT PATHOLOGY, Issue 4 2006
SUGIHIRO ANDO
SUMMARY In clubroot disease, gall formation is induced by infection with the obligate biotroph Plasmodiophora brassicae due to increased levels of auxins and cytokinins. Because aldehyde oxidase (AO) may be involved in auxin biosynthesis in plants, we isolated two AO genes (BrAO1 and BrAO2) from Chinese cabbage (Brassica rapa ssp. pekinensis cv. Muso), which are the most similar to AAO1 among Arabidopsis AO genes, and examined their expressions during clubroot development. The expression of BrAO1 was enhanced in inoculated roots from 15 days post-inoculation (dpi) when visible clubroots were still undetectable. Thereafter, BrAO1 expression increased with clubroot development compared with uninoculated roots, although BrAO2 expression was repressed. In situ hybridization revealed that BrAO1 was strongly expressed in tissues that were invaded by immature plasmodia at 35 dpi, suggesting that BrAO1 expression was enhanced by the pathogen in order to establish its pathogenesis. In addition, we detected AO activity, as evidenced by the occurrence of at least six bands (BrAO-a to BrAO-f) in the roots of Chinese cabbage using an active staining method with benzaldehyde and indlole-3-aldehyde as the substrate. Coincidental with BrAO1 expression, the signals of BrAO-a and BrAO-d increased with inoculation by P. brassicae during clubroot development compared with healthy roots, resulting in an increase in total AO activity. By contrast, the band BrAO-b decreased post-inoculation, in parallel with the expression of BrAO2. The other bands of activity were not clearly influenced by the infection. Based on these results, we discuss the involvement of AO in auxin-overproduction during clubroot development in Chinese cabbage. [source]


The maize Viviparous10/Viviparous13 locus encodes the Cnx1 gene required for molybdenum cofactor biosynthesis

THE PLANT JOURNAL, Issue 2 2006
Timothy G. Porch
Summary Abscisic acid (ABA), auxin and nitrate are important signaling molecules that affect plant growth responses to the environment. The synthesis or metabolism of these compounds depends on the molybdenum cofactor (MoCo). We show that maize (Zea mays) viviparous10 (vp10) mutants have strong precocious germination and seedling lethal phenotypes that cannot be rescued with tissue culture. We devised a novel PCR-based method to clone a transposon-tagged allele of vp10, and show that Vp10 encodes the ortholog of Cnx1, which catalyzes the final common step of MoCo synthesis. The seedling phenotype of vp10 mutants is consistent with disruptions in ABA and auxin biosynthesis, as well as a disruption in nitrate metabolism. Levels of ABA and auxin are reduced in vp10 mutants, and vp10 seedlings lack MoCo-dependent enzyme activities that are repairable with exogenous molybdenum. vp10 and an Arabidopsis cnx1 mutant, chlorate6 (chl6), have similar defects in aldehyde oxidase (AO) enzyme activity, which is required for ABA synthesis. Surprisingly, chl6 mutants do not show defects in abiotic stress responses. These observations confirm an orthologous function for Cnx1 and Vp10, as well as defining a characteristic viviparous phenotype to identify other maize cnx mutants. Finally, the vp10 mutant phenotype suggests that cnx mutants can have auxin- as well as ABA-biosynthesis defects, while the chl6 mutant phenotype suggests that low levels of AO activity are sufficient for normal abiotic stress responses. [source]


Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation

ARTHRITIS & RHEUMATISM, Issue 8 2009
Joseph E. Baggott
Objective To assess the catabolism of methotrexate (MTX) to 7-hydroxy-MTX (7-OH-MTX) in patients with rheumatoid arthritis as well as the effect of folic acid and folinic acid on this catabolism. Methods Urinary excretion of MTX and its catabolite, 7-OH-MTX, was measured in 2 24-hour urine specimens collected after MTX therapy. Urine samples were collected from patients after the sixth and seventh weekly doses of MTX. MTX and 7-OH-MTX concentrations were determined by high-performance liquid chromatography mass spectrometry. Swelling and pain/tenderness indices were used to measure symptoms before and at 6 and 7 weeks of therapy. Patients received either folic acid or folinic acid supplements (1 mg/day) from week 6 to week 7. Results Folic acid inhibited aldehyde oxidase (AO), the enzyme that produces 7-OH-MTX, but folinic acid did not. Excretion of 7-OH-MTX (determined as a percentage of the dose of MTX or as mg 7-OH-MTX/gm creatinine) was not normally distributed (n = 39). Patients with marked improvement in swelling and pain/tenderness indices had a lower mean 7-OH-MTX excretion level (P < 0.05). Patients who received folic acid supplements had decreased 7-OH-MTX excretion (P = 0.03). Relatively high 7-OH-MTX excretion was correlated with relatively high MTX excretion and with relatively low MTX retention in vivo (P < 0.05) (n = 35). Conclusion Our findings of a non-normal distribution of 7-OH-MTX excretion suggest that there are at least 2 phenotypes for this catabolism. Decreased 7-OH-MTX formation suggests folic acid inhibition of AO and a better clinical response, while increased 7-OH-MTX formation may interfere with MTX polyglutamylation and binding to enzymes and, therefore, may increase MTX excretion and decrease MTX retention and efficacy in vivo. [source]


Cell biology of molybdenum

BIOFACTORS, Issue 5 2009
Ralf R. Mendel
Abstract The transition element molybdenum (Mo) is an essential micronutrient that is needed as catalytically active metal during enzyme catalysis. In humans four enzymes depend on Mo: sulfite oxidase, xanthine oxidoreductase, aldehyde oxidase, and mitochondrial amidoxime reductase. In addition to these enzymes, plants harbor a fifth Mo-enzyme namely nitrate reductase. To gain biological activity and fulfill its function in enzymes, Mo has to be complexed by a pterin compound thus forming the molybdenum cofactor. This article will review the way that Mo takes from uptake into the cell, via formation of the molybdenum cofactor and its storage, up to the final insertion of the molybdenum cofactor into apometalloenzymes. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [source]


Species differences in enantioselective 2-oxidations of RS-8359, a selective and reversible MAO-A inhibitor, and cinchona alkaloids by aldehyde oxidase

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 3 2006
Kunio Itoh
Abstract The 2-oxidation activity on the pyrimidine ring of RS-8359, a MAO-A inhibitor, is the major metabolic pathway catalysed by aldehyde oxidase. This study investigated the species differences in the 2-oxidation activity by using liver cytosolic fractions from rats, mice, guinea-pigs, rabbits, dogs, monkeys and humans. The Vmax/Km value for the (S)-enantiomer of RS-8359 was extremely high in monkeys and humans, moderate in guinea-pigs, and low in rats and mice. Dogs were deficient in 2-oxidation activity. The (R)-enantiomer was only oxidized at a very low rate in guinea-pigs, monkeys and humans, and not oxidized in rats, mice and rabbits. Thus, marked species differences and enantioselectivity were obvious for the 2-oxidation of the (S)-enantiomer of RS-8359. The in vitro results were in good accordance with previously reported in vivo excretion data of the 2-keto metabolite and the non-detectable plasma concentrations of the (S)-enantiomer in monkeys and humans after administration of racemic RS-8359. Enantioselectivity was also observed for the oxidation of cinchona alkaloids catalysed by aldehyde oxidase. Among the four cinchona alkaloids studied, the oxidation activity of cinchonidine, which has no substituents at the 6-hydroxy group but bears (8S,9R)-configurations, was highest. As opposed to the (S)-enantiomer, an extremely high catalytic activity of cinchonidine was confirmed in rabbits, but not in monkeys or humans. Rabbit liver aldehyde oxidase was suggested to have characteristic properties around the active site. Copyright © 2006 John Wiley & Sons, Ltd. [source]


Stereoselective pharmacokinetics of RS-8359, a selective and reversible MAO-A inhibitor, by species-dependent drug-metabolizing enzymes

CHIRALITY, Issue 3 2005
Wataru Takasaki
Abstract RS-8359, (±)-4-(4-cyanoanilino)-5,6-dihydro-7-hydroxy-7H -cyclopenta[d]pyrimidine selectively and reversibly inhibits monoamine oxidase A (MAO-A). After oral administration of rac -RS-8359 to rats, mice, dogs, monkeys, and humans, plasma concentrations of the (R)-enantiomer were greatly higher than were those of the (S)-enantiomer in all species studied. The AUC(R) to AUC(S) ratios were 2.6 in rats, 3.8 in mice, 31 in dogs, and 238 in monkeys, and the (S)-enantiomer was almost negligible in human plasma. After intravenous administration of RS-8359 enantiomers to rats, the pharmacokinetic parameters showed that the (S)-enantiomer had a 2.7-fold greater total clearance (CLt) and a 70% shorter half-life (t1/2) than those for the (R)-enantiomer but had no difference in distribution volume (Vd). No significant difference in the intestinal absorption rate was observed. The principal metabolites were the 2-keto form, possibly produced by aldehyde oxidase, the cis -diol form, and the 2-keto- cis -diol form produced by cytochrome P450 in rats, the cis -diol form in mice, RS-8359 glucuronide in dogs, and the 2-keto form in monkeys and humans. Thus, the rapid disappearance of the (S)-enantiomer from the plasma was thought to be due to the rapid metabolism of the (S)-enantiomer by different drug-metabolizing enzymes, depending on species. Chirality 17:135,141, 2005. © 2005 Wiley-Liss, Inc. [source]