Aldehyde Oxidase Activity and Stability in Water-Miscible Organic Solvents

Rashidi, Mohammad-Reza; Dehghany, Moharam; Dehghan, G.; Jouyban, Abolghasem; Faridi, Akram

doi:10.1007/s12010-012-0036-7

Cited by 7 publications

(6 citation statements)

References 21 publications

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“…The crystal structures of hAOX1 in the substrate-free form [Protein Data Bank (PDB) ID: 4UHW] and in complex with the substrate phthalazine and the noncompetitive inhibitor thioridazine (PDB ID: 4UHX) are known and contributed with novel and important structural features to the clarification of the role of hAOX1 in drug metabolism [10]. However, despite the extensive ongoing investigations on the role of AOXs in drug metabolism, there are only very few studies reporting the stability of enzymes from this family not taking into account structural aspects [14].…”

Section: Databasesmentioning

confidence: 99%

Human aldehyde oxidase (hAOX1): structure determination of the Moco‐free form of the natural variant G1269R and biophysical studies of single nucleotide polymorphisms

et al. 2019

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Human aldehyde oxidase ( hAOX 1) is a molybdenum enzyme with high toxicological importance, but its physiological role is still unknown. hAOX 1 metabolizes different classes of xenobiotics and is one of the main drug‐metabolizing enzymes in the liver, along with cytochrome P450. hAOX 1 oxidizes and inactivates a large number of drug molecules and has been responsible for the failure of several phase I clinical trials. The interindividual variability of drug‐metabolizing enzymes caused by single nucleotide polymorphisms ( SNP s) is highly relevant in pharmaceutical treatments. In this study, we present the crystal structure of the inactive variant G1269R, revealing the first structure of a molybdenum cofactor (Moco)‐free form of hAOX 1. These data allowed to model, for the first time, the flexible Gate 1 that controls access to the active site. Furthermore, we inspected the thermostability of wild‐type hAOX 1 and hAOX 1 with various SNP s (L438V, R1231H, G1269R or S1271L) by CD spectroscopy and Thermo FAD , revealing that amino acid exchanges close to the Moco site can impact protein stability up to 10 °C. These results correlated with biochemical and structural data and enhance our understanding of hAOX 1 and the effect of SNP s in the gene encoding this enzyme in the human population. Enzymes Aldehyde oxidase ( EC1.2.3.1 ); xanthine dehydrogenase ( EC1.17.1.4 ); xanthine oxidase ( EC1.1.3.2 ). Databases Structural data are available in the Protein Data Bank under the accession number 6Q6Q .

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Section: Databasesmentioning

confidence: 99%

Human aldehyde oxidase (hAOX1): structure determination of the Moco‐free form of the natural variant G1269R and biophysical studies of single nucleotide polymorphisms

et al. 2019

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“…In vitro enzyme catalytic activity in solvent containing mixtures can also be altered, due to a variety of reasons like change in conformation, active center blockage, competitive metabolism of solvent, limited diffusion, and accessibility of substrate to the enzyme, unfavorable energetics of substrate desolvation, etc., [30] . In several studies, the catalytic ability of cytochrome P450, a family of isozymes responsible for the metabolism of the majority of the marketed drugs, and few other enzymes are shown to be altered by different types of water- miscible solvents used (Table 11) [31][32][33][34][35] . In most cases, the alteration in activity is concentrationdependent i.e., more the solvent used higher is the alteration in activity making it necessary to limit the use of solvents within the acceptable range.…”

Section: Table 2: Scores Of Solvents Based On Percent Inhibition Of C...mentioning

confidence: 99%

In Vitro Studies on the Effects of Water Miscible Organic Co-Solvents on Select Drug Metabolizing Enzyme Activities

Iyer,

Kamble,

Shah

et al. 2024

IJPS

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Iyer et al.: Effect of Organic Solvents on Drug Metabolizing EnzymesOrganic solvents are extensively used in in vitro drug metabolism studies to overcome the solubility issues of lipophilic substrate/new chemical entities. The effects of ten common water miscible organic solvents on cytochrome P450s and non-cytochrome P450 enzymes, namely, flavin monooxygense, aldehyde oxidase, xanthine oxidase, esterases and glutathione S-transferases were evaluated. Rat liver microsomes and rat liver cytosol were used for cytochrome P450, flavin monooxygenase and glutathione S-transferase assays. Partially purified guinea pig liver aldehyde oxidase and rat liver xanthine oxidase fractions were used for molybdenum hydroxylase activity assays. Human plasma was used for esterase activity. Para-nitro phenol, metoprolol, imipramine, methyl para-tolyl sulfide, para-nitrophenyl acetate, vanillin, xanthine and chloro dinitrobenzene, were used as substrates for evaluating CYP2E1, CYP2D6, CYP1A2, flavin monooxyenase, esterase, aldehyde oxidase, xanthine oxidase and glutathione S-transferase activities, respectively. Ten solvents (acetonitrile, acetone, dioxane, dimethyl formamide, dimethyl sulfoxide, ethanol, methanol, polyethylene glycol 400, n-propanol, and isopropanol) were evaluated at four concentrations (0.1, 0.25, 0.5 and 1 % v/v). The following results were obtained. Dioxane (1 % v/v) was found to a potent inhibitor inhibiting all the tested CYP's (>90 % inhibition) and flavin monooxygenase (71 % inhibition). Seven of ten organic solvents inhibited esterases in a concentration dependent manner out of which n-propanol showed the maximal inhibition (79 % inhibition). Methanol was the only solvent that inhibited aldehyde oxidase (78 % inhibition) and xanthine oxidase mediated metabolism (64 % inhibition). Minimal inhibition effect was observed on glutathione S-transferase mediated activity by all solvents. Polyethylene glycol 400 showed least inhibition of enzyme activities. Among the 10 solvents studies, acetonitrile overall appears to be the safest organic solvent at concentrations of 1 % v/v or less. The results of this study indicate that many water miscible organic solvents must be used very judiciously in drug metabolism studies.

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“…Oligosaccharides have become increasingly attractive as new food ingredients because of their potential to improve the quality and nutritional properties of food [1]. As a main category of oligosaccharides, isomaltooligosaccharides (IMO) contain 2-5 glucose units with one or more a- (1,6) linkages. IMO are attracting considerable interest in the food industry because of their bifidus-stimulating activity, low caloric value, and low cariogenic properties [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…IMO are attracting considerable interest in the food industry because of their bifidus-stimulating activity, low caloric value, and low cariogenic properties [2,3]. At present, IMO are manufactured through enzymatic processes, wherein an a-glucosidase from Aspergillus niger catalyzes transglycosylation to the 6-OH of the accepting glucose unit, resulting in formation of new (1,6)oligosaccharides such as isomaltose, panose, and isomaltotriose [4].…”

Section: Introductionmentioning

confidence: 99%

“…Enzymes have been applied for the catalytic processes in organic-aqueous media due to their industrially attractive advantages, which include elimination of microbial contamination in the reaction mixtures, shifting of thermodynamic equilibrium to favor synthesis over hydrolysis, reduction in undesirable side reactions, and variations of specificity of some enzymes [6,7]. The production processes of oligosaccharides in organic-aqueous systems have been extensively studied.…”

Section: Introductionmentioning

confidence: 99%

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Improved synthesis of isomaltooligosaccharides using immobilized α-glucosidase in organic–aqueous media

Wang

Niu

et al. 2017

Food Sci Biotechnol

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α-Glucosidase was immobilized onto an epoxy-activated resin (Eupergit C) to catalyze maltose into isomaltooligosaccharides (IMO), and then the effects of organic-aqueous media on the enzymatic properties of immobilized α-glucosidase were examined. An immobilization efficiency of 79.61% was obtained under the condition of pH 6.0, ionic strength of 2.0 M, and 30 mg of protein/g of resin. The butyl acetate-aqueous biphasic system was found to significantly improve the catalytic activity of the immobilized enzyme and the yield of IMO. The highest yield of IMO (50.83%, w/w) was obtained at pH 4.5 and 55 °C in a butyl acetate/buffer system (25:75, v/v). In addition, the immobilized enzyme particles were distributed into the organic phase after the completion of transglycosylation, which facilitates the separation and recycling use of the immobilized enzyme. Immobilized α-glucosidase retains a robust reusability in this continuous operation model. The present findings are of potential in improving the IMO manufacturing process.

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Aldehyde Oxidase Activity and Stability in Water-Miscible Organic Solvents

Cited by 7 publications

References 21 publications

Human aldehyde oxidase (hAOX1): structure determination of the Moco‐free form of the natural variant G1269R and biophysical studies of single nucleotide polymorphisms

Human aldehyde oxidase (hAOX1): structure determination of the Moco‐free form of the natural variant G1269R and biophysical studies of single nucleotide polymorphisms

In Vitro Studies on the Effects of Water Miscible Organic Co-Solvents on Select Drug Metabolizing Enzyme Activities

Improved synthesis of isomaltooligosaccharides using immobilized α-glucosidase in organic–aqueous media

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