Hydroxylation of 4-amino-antifolates by partially purified aldehyde oxidase from rabbit liver

Fabre, Gérard; Seither, Richard L.; Goldman, I. David

doi:10.1016/0006-2952(86)90277-7

Cited by 29 publications

(17 citation statements)

References 22 publications

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“…This may be attributed to a decrease in the level of cytochrome P-450, which is responsible for antipyrine metabo lism [18], as a result of a reduced number of in tact hepatic parenchymal cells and reduction in functional hepatic mass [6,13,19], Bilharzial infestation caused a significant reduction in p and Cl as well as an increase in the ty,|j and AUC of MTX. This may be due to partial liver impairment induced by bilharzial infestation, for liver was found to be the major site of de toxification of MTX [20]. Moreover, it is worth mentioning that the 7-OH derivative of MTX, a metabolic product of MTX, may limit MTX toxicity [21] to dividing cells by interfering with MTX uptake [22] and polyglutamylation [23,24].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Profile of Methotrexate and 5-Fluorouracil in Normal and Bilharzial-infested Mice

Osman

Saad²,

Saad³

et al. 1994

Chemotherapy

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The pharmacokinetics of two commonly used anticancer drugs, methotrexate (MTX) and 5-fluorouracil (5-FU), were investigated in normal and bilharzial-infested mice. Liver glu-cose-6-phosphatase activity and antipyrine clearance were used as parameters of liver function. Liver glucose-6-phospha-tase activity was significantly reduced in bilharzial-infested mice compared with the normal controls. Bilharzial infestation caused a significant reduction in the elimination (β) and clearance rate (CI) of antipyrine, whereas its elimination half-life (t_½β) was increased in comparison with the normal controls. A similar pattern was also obtained after MTX and 5-FU administration in bilharzial mice, compared to controls. These results indicate that hepatic bilharziasis causes a significant reduction in the hepatic clearance and elimination of MTX and 5-FU, whereas their areas under the concentration-time curve were significantly increased. These findings may have to be considered in the treatment of bilharzial cancer patients.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Profile of Methotrexate and 5-Fluorouracil in Normal and Bilharzial-infested Mice

Osman

Saad²,

Saad³

et al. 1994

Chemotherapy

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“…AO is much less studied, and a physiological substrate for the enzyme has not yet been established, although there are reports indicating that the enzyme oxidizes retinaldehyde into retinoic acid (29) and is involved in the catabolism of the monoamine neurotransmitters (30). Moreover, the AO protein is of considerable pharmacological and toxicological importance, given its role in the metabolism of drugs such as methotrexate (31) and cyclophosphamide (32). Finally, the AO gene has been recently implicated in the etiopathogenesis of the familial recessive form of amyotrophic lateral sclerosis, a rare motor neuron disease (33).…”

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confidence: 99%

Cloning of the cDNAs Coding for Two Novel Molybdo-flavoproteins Showing High Similarity with Aldehyde Oxidase and Xanthine Oxidoreductase

Terao

Kurosaki

Saltini

et al. 2000

Journal of Biological Chemistry

113

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The cDNAs coding for two novel mouse molybdo-flavoproteins, AOH1 and AOH2 (aldehyde oxidase homolog 1 and 2), were isolated. The AOH1 and AOH2 cDNAs code for polypeptides of 1336 amino acids. The two proteins have similar primary structure and show striking amino acid identity with aldehyde oxidase and xanthine oxidoreductase, two other molybdo-flavoenzymes. AOH1 and AOH2 contain consensus sequences for a molybdopterin-binding site and two distinct 2Fe-2S redox centers. In its native conformation, AOH1 has a molecular weight consistent with a homotetrameric structure. Transfection of the AOH1 and AOH2 cDNAs results in the production of proteins with phenanthridine but not hypoxanthine oxidizing activity. Furthermore, the AOH1 protein has benzaldehyde oxidizing activity with electrophoretic characteristics identical to those of a previously identified aldehyde oxidase isoenzyme (Holmes, R. S. (1979) Biochem. Genet. 17, 517-528). The AOH1 transcript is expressed in the hepatocytes of the adult and fetal liver and in spermatogonia. In liver, the AOH1 protein is synthesized in a gender-specific fashion. The expression of AOH2 is limited to keratinized epithelia and the basal layer of the epidermis and hair folliculi. The selective cell and tissue distribution of AOH1 and AOH2 mRNAs is consistent with the localization of the respective protein products.

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“…Although XOR is the key enzyme in the catabolism of purines, oxidizing hypoxanthine to xanthine and xanthine to uric acid (7,8), the physiological function of AO is still unknown, although the enzyme is involved in the metabolism of drugs and xenobiotics of toxicological importance (9,10). AO and XOR have similar primary and secondary structure (1) and utilize an overlapping set of substrates (11).…”

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confidence: 99%

Purification of the Aldehyde Oxidase Homolog 1 (AOH1) Protein and Cloning of the AOH1 and Aldehyde Oxidase Homolog 2 (AOH2) Genes

Terao¹,

Kurosaki²,

Marini³

et al. 2001

Journal of Biological Chemistry

111

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We report the cloning of the AOH1 and AOH2 genes, which encode two novel mammalian molybdo-flavoproteins. We have purified the AOH1 protein to homogeneity in its catalytically active form from mouse liver. Twenty tryptic peptides, identified or directly sequenced by mass spectrometry, confirm the primary structure of the polypeptide deduced from the AOH1 gene. The enzyme contains one molecule of FAD, one atom of molybdenum, and four atoms of iron per subunit and shows spectroscopic features similar to those of the prototypic molybdo-flavoprotein xanthine oxidoreductase. The AOH1 and AOH2 genes are 98 and 60 kilobases long, respectively, and consist of 35 coding exons. The AOH1 gene has the potential to transcribe an extra leader non-coding exon, which is located downstream of exon 26, and is transcribed in the opposite orientation relative to all the other exons. AOH1 and AOH2 map to chromosome 1 in close proximity to each other and to the aldehyde oxidase gene, forming a molybdo-flavoenzyme gene cluster. Conservation in the position of exon/ intron junctions among the mouse AOH1, AOH2, aldehyde oxidase, and xanthine oxidoreductase loci indicates that these genes are derived from the duplication of an ancestral precursor.

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Hydroxylation of 4-amino-antifolates by partially purified aldehyde oxidase from rabbit liver

Cited by 29 publications

References 22 publications

Pharmacokinetic Profile of Methotrexate and 5-Fluorouracil in Normal and Bilharzial-infested Mice

Pharmacokinetic Profile of Methotrexate and 5-Fluorouracil in Normal and Bilharzial-infested Mice

Cloning of the cDNAs Coding for Two Novel Molybdo-flavoproteins Showing High Similarity with Aldehyde Oxidase and Xanthine Oxidoreductase

Purification of the Aldehyde Oxidase Homolog 1 (AOH1) Protein and Cloning of the AOH1 and Aldehyde Oxidase Homolog 2 (AOH2) Genes

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