Metabolism of 2-phenylethylamine and phenylacetaldehyde by precision-cut guinea pig fresh liver slices

Panoutsopoulos, Georgios I.; Kouretas, D; Gounaris, Elias; Beedham, Christine

doi:10.1007/bf03190585

Cited by 18 publications

(21 citation statements)

References 29 publications

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“…This indicates that aldehyde dehydrogenase activity in cryopreserved guinea pig liver slices is low. Taken with the evidence that isovanillin is not a substrate for guinea pig liver aldehyde oxidase [5,7] it is proposed that, in liver slices, isovanillin is metabolized to isovanillic acid predominantly by aldehyde dehydrogenase activity.…”

Section: Discussionmentioning

confidence: 98%

“…10 -2 mol/l bicarbonate, which was continuously purged with 95% O 2 /5% CO 2 . Precision-cut liver slices were prepared using a manual slicer according to the method of Panoutsopoulos et al [5]. The first and last slices from each core were discarded because they contained the liver capsule.…”

Section: Preparation Of Freshly Prepared and Cryopreserved Guinea Pigmentioning

confidence: 99%

“…Precision-cut liver slices are often used for in vitro drug metabolism of xenobiotics and toxicological studies [5,[23][24][25]. They are easily prepared from different animal species and they resemble the organ from which they are derived.…”

Section: Introductionmentioning

confidence: 99%

“…Aldehydes are also produced from drugs that contain an amino group attached to an unsubstituted methylene carbon via monoamine oxidase. In addition, biogenic amines can be transformed into endogenous aldehydes by the action of monoamine oxidase [4][5][6]. Although xenobiotic and biogenic aldehydes can be reduced by aldehyde reductase and/or alcohol dehydrogenase to the corresponding alcohols, the main metabolic route is their oxidation to acids which is catalyzed by aldehyde dehydrogenase (EC 1.2.1.3, aldehyde-NAD(P) + oxidoreductase), aldehyde oxidase (EC 1.2.3.1, aldehydeoxygen oxidoreductase) and/or xanthine oxidase (EC 1.2.3.2, xanthine-oxygen oxidoreductase).…”

Section: Introductionmentioning

confidence: 99%

“…10 -4 mol/l) [7] but a potent competitive inhibitor of guinea pig liver aldehyde oxidase [5,7,28] with a K i value of 6.64 ! 10 -7 mol/l [7].…”

Section: Introductionmentioning

confidence: 99%

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Metabolism of Isovanillin by Aldehyde Oxidase, Xanthine Oxidase, Aldehyde Dehydrogenase and Liver Slices

Panoutsopoulos

Beedham

2005

Pharmacology

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Aromatic aldehydes are good substrates of aldehyde dehydrogenase activity but are relatively poor substrates of aldehyde oxidase and xanthine oxidase. However, the oxidation of xenobiotic-derived aromatic aldehydes by the latter enzymes has not been studied to any great extent. The present investigation compares the relative contribution of aldehyde dehydrogenase, aldehyde oxidase and xanthine oxidase activities in the oxidation of isovanillin in separate preparations and also in freshly prepared and cryopreserved liver slices. The oxidation of isovanillin was also examined in the presence of specific inhibitors of each oxidizing enzyme. Minimal transformation of isovanillin to isovanillic acid was observed in partially purified aldehyde oxidase, which is thought to be due to residual xanthine oxidase activity. Isovanillin was rapidly metabolized to isovanillic acid by high amounts of purified xanthine oxidase, but only low amounts are present in guinea pig liver fraction. Thus the contribution of xanthine oxidase to isovanillin oxidation in guinea pig is very low. In contrast, isovanillin was rapidly catalyzed to isovanillic acid by guinea pig liver aldehyde dehydrogenase activity. The inhibitor studies revealed that isovanillin was predominantly metabolized by aldehyde dehydrogenase activity. The oxidation of xenobiotic-derived aromatic aldehydes with freshly prepared or cryopreserved liver slices has not been previously reported. In freshly prepared liver slices, isovanillin was rapidly converted to isovanillic acid, whereas the conversion was very slow in cryopreserved liver slices due to low aldehyde dehydrogenase activity. The formation of isovanillic acid was not altered by allopurinol, but considerably inhibited by disulfiram. It is therefore concluded that isovanillin is predominantly metabolized by aldehyde dehydrogenase activity, with minimal contribution from either aldehyde oxidase or xanthine oxidase.

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Section: Discussionmentioning

confidence: 98%

Section: Preparation Of Freshly Prepared and Cryopreserved Guinea Pigmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…10 -4 mol/l) [7] but a potent competitive inhibitor of guinea pig liver aldehyde oxidase [5,7,28] with a K i value of 6.64 ! 10 -7 mol/l [7].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Metabolism of Isovanillin by Aldehyde Oxidase, Xanthine Oxidase, Aldehyde Dehydrogenase and Liver Slices

Panoutsopoulos

Beedham

2005

Pharmacology

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In Vitro and In Silico Studies to Explore Structural Features of Flavonoids for Aldehyde Oxidase Inhibition

Hamzeh‐Mivehroud

Rahmani

Feizi

et al. 2014

Archiv der Pharmazie

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Aldehyde oxidase (AO), an important enzyme in the biotransformation of drugs and xenobiotics, is inhibited by flavonoids. This enzyme can metabolize both aldehydes and N-heterocycles. In this work, a set of 15 flavonoids was assessed for inhibitory activity on the AO oxidation of vanillin as an aldehyde substrate. Spectrophotometrically determined IC50 values showed that myricetin, quercetin, and epicatechin were the most potent inhibitors. The results also revealed that the inhibition of vanillin oxidation by flavonoids was stronger than that of phenanthridine oxidation (an N-heterocyclic substrate) as reported previously. In order to investigate the important structural features responsible for the inhibitory effects of the studied flavonoids, a quantitative structure-activity relationship (QSAR) analysis was performed. This study showed that the size of the flavonoids was the most important factor inversely affecting their potencies. The QSAR model can be used more broadly to predict the AO inhibitory activity of flavonoid-like structures for application in food-drug and drug-drug interaction studies.

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Aldehyde Oxidase Activity and Stability in Water-Miscible Organic Solvents

Rashidi

Dehghany

Dehghan

et al. 2013

Appl Biochem Biotechnol

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In this study, the catalytic activity of aldehyde oxidase was investigated in various water-miscible organic solvents for the first time. The enzyme was partially purified from rabbit liver, and its activity was determined in the absence/presence of nine hydro-organic mixtures. The effects of pH and temperature on the enzyme activity were also investigated. The activity was reduced in the presence of all nine organic solvents. However, in some cases, the residual activity remained almost unchanged throughout the incubation of enzyme at 35 °C for 24 h. Considering potential advantages of doing reactions in the presence of organic solvents, these results could be of value. The enzyme showed different behavior in the reaction solutions making it difficult to formulate results in a single comprehensive model. The results indicated that binding and cleavage of the substrate are influenced in the presence of organic solvents.

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Metabolism of 2-phenylethylamine and phenylacetaldehyde by precision-cut guinea pig fresh liver slices

Cited by 18 publications

References 29 publications

Metabolism of Isovanillin by Aldehyde Oxidase, Xanthine Oxidase, Aldehyde Dehydrogenase and Liver Slices

Metabolism of Isovanillin by Aldehyde Oxidase, Xanthine Oxidase, Aldehyde Dehydrogenase and Liver Slices

In Vitro and In Silico Studies to Explore Structural Features of Flavonoids for Aldehyde Oxidase Inhibition

Aldehyde Oxidase Activity and Stability in Water-Miscible Organic Solvents

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