Regulation and Biochemistry of Mouse Molybdo-flavoenzymes

Vila, Roser; Kurosaki, Mami; Barzago, Maria Monica; Kolek, Metodej; Bastone, Antonio; Colombo, Laura; Salmona, Mario; Terao, Mineko; Garattini, Enrico

doi:10.1074/jbc.m308137200

Cited by 40 publications

(48 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…That both chicken and dog livers are devoid of aldehyde oxidase immunoreactivity is different from what was observed in humans, mice, and rats, where the hepatic tissue is one of the richest source of AOX1 and/or AOH1 (26,49,50). Aldehydes of physiological, toxicological, and pharmacological interest are potential substrates of both aldehyde oxidases of the MOFE family and aldehyde dehydrogenases.…”

Section: The Tissue Distribution Of the Aldehyde Oxidase Transcripts mentioning

confidence: 68%

“…Determination of Retinaldehyde Oxidase Activity in Tissue Cytosolic Extracts-RAL oxidase activity was measured in chicken liver, kidney, and heart, C57/Bl and DBA/2 mouse liver, as well as dog liver and kidney (26). Organs were dissected, frozen, and stored at Ϫ80°C until processed for the determination of RAL activity.…”

Section: Methodsmentioning

confidence: 99%

“…Dupl 2-AOH1* is ϳ51 kbp long and contains recognizable exons (5,8,17,(25)(26)(27)(28) equivalent to the rodent AOH1 counterparts. The exons of Dupl 2-AOH1* are not transcribed, as no cDNA fragment could ever be isolated, despite the use of various PCR primers and RNA from different organs and tissues.…”

Section: The Chicken Aldehyde Oxidase Cluster Consists Of Two Active mentioning

confidence: 99%

“…3A). Purification of the AOX1 protein was followed by measurement of RAL oxidase activity, as RAL is a natural substrate of the enzyme in other mammalian species (26,42). Quantitative Western blot analysis was also conducted on all the purified fractions with polyclonal antibody raised against bovine AOX1.…”

Section: Purification Of Chicken Kidney Aox1 Demonstrates That the Prmentioning

confidence: 99%

“…For this purpose, liver cytosolic extracts were depleted of NAD ϩ by passage on size exclusion columns and subsequently repleted or not with exogenously added dinucleotide. The results were compared with those obtained in cytosolic extracts of C57/Bl and DBA/2 mice that express high and very low levels, respectively, of both AOX1 and AOH1 (26). Fig.…”

Section: The Tissue Distribution Of the Aldehyde Oxidase Transcripts mentioning

confidence: 99%

See 4 more Smart Citations

Avian and Canine Aldehyde Oxidases

Terao¹,

Kurosaki²,

Barzago

et al. 2006

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Aldehyde oxidases are molybdo-flavoenzymes structurally related to xanthine oxidoreductase. They catalyze the oxidation of aldehydes or N-heterocycles of physiological, pharmacological, and toxicological relevance. Rodents are characterized by four aldehyde oxidases as follows: AOX1 and aldehyde oxidase homologs 1-3 (AOH1, AOH2, and AOH3). Humans synthesize a single functional aldehyde oxidase, AOX1. Here we define the structure and the characteristics of the aldehyde oxidase genes and proteins in chicken and dog. The avian genome contains two aldehyde oxidase genes, AOX1 and AOH, mapping to chromosome 7. AOX1 and AOH are structurally very similar and code for proteins whose sequence was deduced from the corresponding cDNAs. AOX1 is the ortholog of the same gene in mammals, whereas AOH represents the likely ancestor of rodent AOH1, AOH2, and AOH3. The dog genome is endowed with two structurally conserved and active aldehyde oxidases clustering on chromosome 37. Cloning of the corresponding cDNAs and tissue distribution studies demonstrate that they are the orthologs of rodent AOH2 and AOH3. The vestiges of dog AOX1 and AOH1 are recognizable upstream of AOH2 and AOH3 on the same chromosome. Comparison of the complement and the structure of the aldehyde oxidase and xanthine oxidoreductase genes in vertebrates and other animal species indicates that they evolved through a series of duplication and inactivation events. Purification of the chicken AOX1 protein to homogeneity from kidney demonstrates that the enzyme possesses retinaldehyde oxidase activity. Unlike humans and most other mammals, dog and chicken are devoid of liver aldehyde oxidase activity. Molybdo-flavoenzymes (MOFEs)4 constitute a small family of homodimeric oxidoreductases characterized by conserved structures (1). Until a few years ago, it was believed that the family of mammalian MOFEs consisted of only two members, i.e. xanthine oxidoreductase (XOR) (2-4) and the aldehyde oxidase AOX1 5 (5-8). XOR has been extensively studied and is the key enzyme in the catabolism of purines, oxidizing hypoxanthine to xanthine and xanthine to uric acid (9 -14). This function is conserved throughout evolution, as the enzyme is present from bacteria to man (1). In mammals, the protein also plays an important role in milk secretion (15-17) and kidney development (18). The function of AOX1 is ill-defined, and the enzyme lacks a recognized physiological substrate. AOX1 metabolizes N-heterocyclic compounds and aldehydes of pharmacological and toxicological relevance (19 -22). XOR and AOX1 are the products of two genes mapping on distinct chromosomes in rodents and different arms of chromosome 2 in humans (4,7,23,24).Recently, we demonstrated that the family of mammalian MOFEs is larger than originally anticipated (25-28). Mice and rats are endowed with three extra MOFEs structurally and biochemically more similar to AOX1 than to XOR. We named these proteins aldehyde oxidase homologs 1-3 (AOH1, AOH2, and AOH3). In rodents, AOH1 is synthesized predominantly in liver and...

show abstract

Section: The Tissue Distribution Of the Aldehyde Oxidase Transcripts mentioning

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Section: The Chicken Aldehyde Oxidase Cluster Consists Of Two Active mentioning

confidence: 99%

Section: Purification Of Chicken Kidney Aox1 Demonstrates That the Prmentioning

confidence: 99%

Section: The Tissue Distribution Of the Aldehyde Oxidase Transcripts mentioning

confidence: 99%

See 3 more Smart Citations

Avian and Canine Aldehyde Oxidases

Terao¹,

Kurosaki²,

Barzago

et al. 2006

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

Construction of expression system of rabbit aldehyde oxidase cDNA for the clarification of species differences

Liu

Sun

Wang

et al. 2009

Eur. J. Drug Metabol. Pharmacokinet.

View full text Add to dashboard Cite

A remarkably large species difference in cinchonidine oxidation activity catalyzed by aldehyde oxidase (AO) has been known, in particular between rabbit and monkey. As the first step in clarifying the phenomenon from the view point of structures of the active site, we attempted to construct an expression system of rabbit AO cDNA. The nucleotide sequences of cloned full-length rabbit AO cDNA were determined and confirmed to agree completely with those of genome DNA. The expression system in Escherichia coli was constructed in reference to the previously established method for monkey AO. Both expressed rabbit and monkey AO proteins correctly reproduced the remarkable species differences observed in their liver cytosols towards cinchonidine and methotrexate. Namely, the expressed rabbit AO protein showed extremely high activities than did that of monkey AO. A difference in the structure of the active site might be responsible for the substrate-dependent species difference towards the relatively bulky molecules of cinchonidine and methotrexate. The use of molecular biology techniques will be very useful to verify the hypothesis.

show abstract

Mammalian aldehyde oxidases: genetics, evolution and biochemistry

Garattini

Fratelli

Terao

2007

Cell. Mol. Life Sci.

166

184

View full text Add to dashboard Cite

Mammalian aldehyde oxidases are a small group of proteins belonging to the larger family of molybdo-flavoenzymes along with xanthine oxidoreductase and other bacterial enzymes. The two general types of reactions catalyzed by aldehyde oxidases are the hydroxylation of heterocycles and the oxidation of aldehydes into the corresponding carboxylic acids. Different animal species are characterized by a different complement of aldehyde oxidase genes. Humans contain a single active gene, while marsupials and rodents are characterized by four such genes clustering at a short distance on the same chromosome. At present, little is known about the physiological relevance of aldehyde oxidases in humans and other mammals, although these enzymes are known to play a role in the metabolism of drugs and compounds of toxicological importance in the liver. The present article provides an overview of the current knowledge of genetics, evolution, structure, enzymology, tissue distribution and regulation of mammalian aldehyde oxidases.

show abstract

Regulation and Biochemistry of Mouse Molybdo-flavoenzymes

Cited by 40 publications

References 47 publications

Avian and Canine Aldehyde Oxidases

Avian and Canine Aldehyde Oxidases

Construction of expression system of rabbit aldehyde oxidase cDNA for the clarification of species differences

Mammalian aldehyde oxidases: genetics, evolution and biochemistry

Contact Info

Product

Resources

About