Avian and Canine Aldehyde Oxidases

Abstract

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...

The mammalian aldehyde oxidase gene family

“…In addition, fish AOX1 and XOR map to different chromosomes, which is also characteristic of all vertebrates except primates. Some avians (chicken) show evidence of a gene duplication event involving AOX1 and resulting in the production of a new synthenic gene (on chromosome 7), which we named aldehyde oxidase homologue ( AOH ) [22]. AOH is characterised by an identical exon/intron structure, with perfect conservation of exon/intron junctions along the coding sequence.…”

“…It is interesting to notice that the dog is currently the only mammalian species that seems to be lacking AOX1 , in addition to AOX4 . This observation has important implications, as this mammal is devoid of aldehyde oxidase activity in the liver [22]. …”

Identification of Crucial Amino Acids in Mouse Aldehyde Oxidase 3 That Determine Substrate Specificity

“…These genes arose from a series of gene duplication events from a common ancestor and are clustered on a short region of mouse chromosome 1 and rat chromosome 9. All of the products of the mammalian Aox genes have high amino acid sequence similarity and are expressed in a tissue-specific manner in different organisms [3], [19]. It is believed that the various AOX isoforms recognize distinct substrates and carry out different physiological tasks.…”

Identification and Characterization of Aldehyde Oxidase 5 in the Pheromone Gland of the Silkworm (Lepidoptera: Bombycidae)

“…However, the other functions of these active AOXs have in insects is unknown. In particular, it is important to understand the structure–activity relationships of AOX binding and metabolism ( Beedham et al 1987 , Dalvie et al 2012 , Coelho et al 2015 ), species differences ( Beedham et al 1987 , Terao et al 2006 , Dalvie et al 2013 ), AOX variability ( Terao et al 2006 , Adachi et al 2007 , Hutzler et al 2014 , Choughule et al 2015 ), and in vitro activity of AOX ( Stell et al 1989 , Alfaro et al 2009 , Liu et al 2009 ). Silkworm has many types of AOXs.…”