2013
DOI: 10.1124/dmd.113.052985
|View full text |Cite
|
Sign up to set email alerts
|

Evaluation of Rhesus Monkey and Guinea Pig Hepatic Cytosol Fractions as Models for Human Aldehyde Oxidase

Abstract: Aldehyde oxidase (AOX) is a cytosolic enzyme expressed across a wide range of species, including guinea pig and rhesus monkey. These species are believed to be the best preclinical models for studying human AOX-mediated metabolism. We compared AOX activity in rhesus monkeys, guinea pigs, and humans using phthalazine and N-[2-(dimethylamino)ethyl]acridone-4-carboxamide (DACA) as substrates and raloxifene as an inhibitor. Michaelis-Menten kinetics was observed for phthalazine oxidation in rhesus monkey, guinea p… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1

Citation Types

4
22
0

Year Published

2013
2013
2021
2021

Publication Types

Select...
7
1

Relationship

3
5

Authors

Journals

citations
Cited by 32 publications
(26 citation statements)
references
References 31 publications
4
22
0
Order By: Relevance
“…5). These interactions are consistent with previous molecular modeling studies involving the AO substrates zoniporide, DACA, and substituted phthalazines (Dastmalchi and Hamzeh-Mivehrod, 2005;Dalvie et al, 2012;Choughule et al, 2013), supporting the hypothesis that the inhibitors are competing with substrates within the active site. A recent report describing the X-ray crystal structure of quercetin bound to the active site of xanthine oxidase, which is highly homologous to AO, further supports this contention (Cao et al, 2014).…”
Section: Discussionsupporting
confidence: 79%
See 2 more Smart Citations
“…5). These interactions are consistent with previous molecular modeling studies involving the AO substrates zoniporide, DACA, and substituted phthalazines (Dastmalchi and Hamzeh-Mivehrod, 2005;Dalvie et al, 2012;Choughule et al, 2013), supporting the hypothesis that the inhibitors are competing with substrates within the active site. A recent report describing the X-ray crystal structure of quercetin bound to the active site of xanthine oxidase, which is highly homologous to AO, further supports this contention (Cao et al, 2014).…”
Section: Discussionsupporting
confidence: 79%
“…Previous QSAR studies using a series of flavonoid compounds involved rat AO (Hamzeh-Mivehroud et al, 2013; however, given the significant between-species variation in enzyme structure, inhibitory potency of compounds can vary widely (Sahi et al, 2008;Choughule et al, 2013). These results provide a first step toward developing in silico models to predict the human AO inhibitory activity of a xenobiotic solely The final aim of this study was to identify dietary constituents as potential perpetrators of clinically relevant AO-mediated interactions with conventional medications.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Previous reports have indicated potent inhibition (K i = 1.0-51 nM, depending on the reducing substrate) properties of raloxifene for AO and thus this compound has been used to explore AO-mediated biochemistry including reduction [4,13,16]. However, there exists no detailed analysis regarding crossover inhibition of XO by raloxifene.…”
Section: Discussionmentioning
confidence: 98%
“…One caveat to bear in mind is that all of these in vitro experiments were performed using AO/XO from nonhuman sources. Major species differences have already been reported for several compounds metabolized by AO and hence extrapolation of pharmacokinetic data from other mammalian species to humans is not advisable (Choughule et al, 2013;Dalvie et al, 2013). Moreover, mammalian xanthine oxidoreductase (XOR) exists in two interconvertible forms, xanthine oxidase (XO) and xanthine dehydrogenase (XDH).…”
mentioning
confidence: 99%