The mammalian aldehyde oxidase gene family

Garattini, Enrico; Fratelli, Maddalena; Terao, Mineko

doi:10.1186/1479-7364-4-2-119

Cited by 102 publications

(47 citation statements)

References 55 publications

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“…Eukaryotic AOXs are cytosolic proteins which are expressed in many tissues of various organisms, including insects, rodents and humans (10,11). AOXs oxidize purines, pyrimidines and pteridines and are involved in nicotinic acid metabolism (12).…”

Section: Introductionmentioning

confidence: 99%

Evolution, expression, and substrate specificities of aldehyde oxidase enzymes in eukaryotes

Terao

Garattini

Romão

et al. 2020

Journal of Biological Chemistry

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Aldehyde oxidases (AOXs) are a small group of enzymes belonging to the larger family of molybdo-flavoenzymes, along with the well-characterized xanthine oxidoreductase. The two major types of reactions that are catalyzed by AOXs are the hydroxylation of heterocycles and the oxidation of aldehydes to their corresponding carboxylic acids. Different animal species have different complements of AOX genes. The two extremes are represented in humans and rodents; whereas the human genome contains a single active gene (AOX1), those of rodents, such as mice, are endowed with four genes (Aox1-4), clustering on the same chromosome, each encoding a functionally distinct AOX enzyme. It still remains enigmatic why some species have numerous AOX enzymes, whereas others harbor only one functional enzyme. At present, little is known about the physiological relevance of AOX enzymes in humans and their additional forms in other mammals. These enzymes are expressed in the liver and play an important role in the metabolisms of drugs and other xenobiotics. In this review, we discuss the expression, tissue-specific roles, and substrate specificities of the different mammalian AOX enzymes and highlight insights into their physiological roles.

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Section: Introductionmentioning

confidence: 99%

Evolution, expression, and substrate specificities of aldehyde oxidase enzymes in eukaryotes

Terao

Garattini

Romão

et al. 2020

Journal of Biological Chemistry

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“…Retinal is converted to retinol by either alcohol dehydrogenase (EC 1.1.1.1) or retinol dehydrogenase (EC 1.1.1.‐), which is then changed to retinyl ester by various O ‐acyltransferases (EC 2.3.1.‐) (Hoog and Ostberg ; Lee et al, ; Shi and Cheng ). Retinal can also be oxidized by either aldehyde oxidase (EC 1.2.3.1) or retinal dehydrogenase (EC 1.2.1.36) into retinoic acid for degradation (Garattini et al, ).…”

Section: Introductionmentioning

confidence: 99%

Selective retinol production by modulating the composition of retinoids from metabolically engineered E. coli

Jang

Zhou

et al. 2015

Biotech & Bioengineering

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Retinoids can be produced from E. coli when introduced with the β-carotene biosynthesis pathway and the BCMO gene. E. coli has no inherent metabolic pathways related to retinoids, therefore only retinal should be produced from the cleavage of β-carotene by BCMO. However, retinol and retinyl acetate were also produced in significant amounts, by the non-specific activity of inherent promiscuous enzymes or the antibiotic resistance marker of the retinal-producing plasmids. Retinol was produced by the ybbO gene of E. coli which encodes oxidoreductase and retinyl acetate was produced by the chloramphenicol resistance gene, called cat gene which encodes chloramphenicol acetyltransferase, present within the pS-NA plasmid that also contains the mevalonate pathway. The composition of retinoids could be modulated by manipulating the relevant genes. The composition of retinol, a commercially important retinoid, was significantly increased by the overexpression of ybbO gene and the removal of cat gene in the recombinant E. coli, which suggests the possibility of selective retinoid production in the future.

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“…It formed hydrogen bonds with Gln1040, Ser1082, Gln1261, Gly797, Gln767, Cys150, and Lys1045. 126 A series of 7-methyl-2-(phenoxymethyl)-5H- [1,3,4] Sathisha and colleagues demonstrated a significant XO inhibition and were much more potent than allopurinol. The order of potency for the synthesized compounds was reported to be 6 > 8 > 7 > 9.…”

Section: Synthetic Nonpurine Analogsmentioning

confidence: 99%

“…Liver is the main site of expression of human AOX1; however, it is also expressed in kidney, liver, lung, small, and large intestine. 3,9 Liver peroxidation and amino acid oxidation result in the formation of endogenous aldehyde. AOX catalyzes the oxidation of aldehyde to the corresponding carboxylic acid, and in the case of N-heterocyclic compounds, it involves the oxidation of carbon atom adjacent to the nitrogen atom by the nucleophilic mechanism.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…Xanthine oxidase (XO; EC 1.17.3.2) and aldehyde oxidase (AOX; EC 1.2.3.1) are the cytosolic enzymes present in various vertebrates including humans. [1][2][3][4] They belong to a molybdoflavoprotein family. Both the enzymes are homologous to each other and have 145 kDa (XO) 5 and 150 kDa (AOX) 6 both are collectively called as xanthine oxidoreductase (XOR).…”

Section: Introductionmentioning

confidence: 99%

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Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

Kumar

Joshi

Kler

et al. 2017

Medicinal Research Reviews

101

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Almost all drug molecules become the substrates for oxidoreductase enzymes, get metabolized into more hydrophilic products and eliminated from the body. These metabolites sometime may be more potent, active, inactive, or toxic in nature compared to parent molecule. Xanthine oxidoreductase and aldehyde oxidase belong to molybdenum containing family and are well characterized for their structures and functions, in particular to their ability to oxidize/hydroxylate the xenobiotics. Their upregulated clinical levels causing oxidative stress are associated with pathways either directly involved in the progression of diseases, gout, or indirectly with the succession of other diseases such as diabetes, cancer, etc. Herein, we have put forth a comprehensive review on the xanthine and aldehyde oxidases pertaining to their structures, functions, pathophysiological role, and a comparative analysis of structural insights of xanthine and aldehyde oxidases' binding domains with endogenous ligands or inhibitors. Though both the enzymes are molybdenum containing and are likely to share some common pathways and interact with inhibitors in a similar manner but we have focused on structural prerequisites for inhibitor specificity to both the enzymes keeping in view of the existing X-ray structures. This review also provides futuristic implications in the design of inhibitors derived from inorganic complexes or small organic molecules considering the spatial features and structural insights of both the enzymes.

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The mammalian aldehyde oxidase gene family

Cited by 102 publications

References 55 publications

Evolution, expression, and substrate specificities of aldehyde oxidase enzymes in eukaryotes

Evolution, expression, and substrate specificities of aldehyde oxidase enzymes in eukaryotes

Selective retinol production by modulating the composition of retinoids from metabolically engineered E. coli

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

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