Substrate specificity of guinea pig liver aldehyde oxidase and bovine milk xanthine oxidase for methyl- and nitrobenzaldehydes

2006 ◽  
Vol 31 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Aristidis S. Veskoukis ◽  
Demetrios Kouretas ◽  
Georgios I. Panoutsopoulos
Keyword(s):  
Guinea Pig ◽  
Substrate Specificity ◽  
Xanthine Oxidase ◽  
Bovine Milk ◽  
Aldehyde Oxidase ◽  
Pig Liver ◽  
Guinea Pig Liver

scholarly journals Kinetics and specificity of guinea pig liver aldehyde oxidase and bovine milk xanthine oxidase towards substituted benzaldehydes.

2004 ◽  
Vol 51 (3) ◽  
pp. 649-663 ◽  
Author(s):  
Georgios I Panoutsopoulos ◽  
Christine Beedham
Keyword(s):  
Guinea Pig ◽  
Xanthine Oxidase ◽  
Oxidase Activity ◽  
Bovine Milk ◽  
Aromatic Aldehydes ◽  
Aldehyde Oxidase ◽  
Inhibitory Effect ◽  
Pig Liver ◽  
Alkyl Benzenes ◽  
Guinea Pig Liver

Molybdenum-containing enzymes, aldehyde oxidase and xanthine oxidase, are important in the oxidation of N-heterocyclic xenobiotics. However, the role of these enzymes in the oxidation of drug-derived aldehydes has not been established. The present investigation describes the interaction of eleven structurally related benzaldehydes with guinea pig liver aldehyde oxidase and bovine milk xanthine oxidase, since they have similar substrate specificity to human molybdenum hydroxylases. The compounds under test included mono-hydroxy and mono-methoxy benzaldehydes as well as 3,4-dihydroxy-, 3-hydroxy-4-methoxy-, 4-hydroxy-3-methoxy-, and 3,4-dimethoxy-benzaldehydes. In addition, various amines and catechols were tested with the molybdenum hydroxylases as inhibitors of benzaldehyde oxidation. The kinetic constants have shown that hydroxy-, and methoxy-benzaldehydes are excellent substrates for aldehyde oxidase (Km values 5x10(-6) M to 1x10(-5) M) with lower affinities for xanthine oxidase (Km values around 10(-4) M). Therefore, aldehyde oxidase activity may be a significant factor in the oxidation of the aromatic aldehydes generated from amines and alkyl benzenes during drug metabolism. Compounds with a 3-methoxy group showed relatively high Vmax values with aldehyde oxidase, whereas the presence of a 3-hydroxy group resulted in minimal Vmax values or no reaction. In addition, amines acted as weak inhibitors, whereas catechols had a more pronounced inhibitory effect on the aldehyde oxidase activity. It is therefore possible that aldehyde oxidase may be critical in the oxidation of the analogous phenylacetaldehydes derived from dopamine and noradrenaline.

Phenylacetaldehyde Oxidation by Freshly Prepared and Cryopreserved Guinea Pig Liver Slices: The Role of Aldehyde Oxidase

2005 ◽  
Vol 24 (2) ◽  
pp. 103-109 ◽  
Author(s):  
Georgios I. Panoutsopoulos
Keyword(s):  
Guinea Pig ◽  
Xanthine Oxidase ◽  
Aldehyde Dehydrogenase ◽  
Phenylacetic Acid ◽  
Aldehyde Oxidase ◽  
Acid Formation ◽  
Pig Liver ◽  
Liver Slices ◽  
Inhibited Acid ◽  
Guinea Pig Liver

Phenylacetaldehyde is formed when the xenobiotic and biogenic amine 2-phenylethylamine is inactivated by a monoamine oxidase–catalyzed oxidative deamination. Exogenous phenylacetaldehyde is found in certain foodstuffs such as honey, cheese, tomatoes, and wines. 2-Phenylethylamine can trigger migraine attacks in susceptible individuals and can become fairly toxic at high intakes from foods. It may also function as a potentiator that enhances the toxicity of histamine and tyramine. The present investigation examines the metabolism of phenylacetaldehyde to phenylacetic acid in freshly prepared and in cryopreserved guinea pig liver slices. In addition, it compares the relative contribution of aldehyde oxidase, xanthine oxidase, and aldehyde dehydrogenase in the oxidation of phenylacetaldehyde using specific inhibitors for each oxidizing enzyme. The inhibitors used were isovanillin for aldehyde oxidase, allopurinol for xanthine oxidase, and disulfiram for aldehyde dehydrogenase. In freshly prepared liver slices, phenylacetaldehyde was converted mainly to phenylacetic acid, with traces of 2-phenylethanol being present. Disulfiram inhibited phenylacetic acid formation by 80% to 85%, whereas isovanillin inhibited acid formation to a lesser extent (50% to 55%) and allopurinol had little or no effect. In cryopreserved liver slices, phenylacetic acid was also the main metabolite, whereas the 2-phenylethanol production was more pronounced than that in freshly prepared liver slices. Isovanillin inhibited phenylacetic acid formation by 85%, whereas disulfiram inhibited acid formation to a lesser extent (55% to 60%) and allopurinol had no effect. The results in this study have shown that, in freshly prepared and cryopreserved liver slices, phenylacetaldehyde is converted to phenylacetic acid by both aldehyde dehydrogenase and aldehyde oxidase, with no contribution from xanthine oxidase. Therefore, aldehyde dehydrogenase is not the only enzyme responsible in the metabolism of phenylacetaldehyde, but aldehyde oxidase may also be important and thus its role should not be ignored.

Substrate specificity of guinea pig liver flavin-containing monooxygenase for morphine, tropane and strychnos alkaloids

1990 ◽  
Vol 40 (10) ◽  
pp. 2380-2382 ◽  
Author(s):  
Koichiro Yuno ◽  
Hideyuki Yamada ◽  
Kazuta Oguri ◽  
Hidetoshi Yoshimura
Keyword(s):  
Guinea Pig ◽  
Substrate Specificity ◽  
Pig Liver ◽  
Guinea Pig Liver

scholarly journals Simultaneous formation of 2- and 4-quinolones from quinolinium cations catalysed by aldehyde oxidase

1984 ◽  
Vol 220 (1) ◽  
pp. 67-74 ◽  
Author(s):  
S M Taylor ◽  
C Stubley-Beedham ◽  
J G P Stell
Keyword(s):  
Guinea Pig ◽  
Aldehyde Oxidase ◽  
Oxidation Products ◽  
Pig Liver ◽  
Simultaneous Formation ◽  
Ph Values ◽  
Quaternary Compounds ◽  
Guinea Pig Liver ◽  
Quinolinium Salts

Quinolinium salts were incubated with partially purified aldehyde oxidase, and the products were separated by high-pressure liquid chromatography and fully characterized by u.v. spectroscopy, i.r. spectroscopy and mass spectrometry. Oxidation of N-methylquinolinium salts with either rabbit or guinea-pig liver aldehyde oxidase in vitro gave two isomeric products, N-methyl-4-quinolone and N-methyl-2-quinolone. Incubation of N-phenylquinolinium perchlorate similarly yielded two oxidation products, N-phenyl-4-quinolone and N-phenyl-2-quinolone. The ratio of 2- to 4-quinolone production was species-dependent, the proportion of 4-quinolone with the guinea-pig enzyme being greater than that obtained with the rabbit liver enzyme. Kinetic constants were determined spectrophotometrically for both the quinolinium salts and a number of related quaternary compounds. In general, quaternization facilitated oxidation of a substrate, but a number of exceptions were noted, e.g. N-methylisoquinolinium and N-methylphen-anthridinium. Km values varied with the nature of electron acceptor employed, and this difference was more marked for quaternary substrates than the unquaternized counterparts. The product ratio obtained from N-methylquinolinium salts was found to be constant under various conditions, including purification of the enzyme and the use of either induced or inhibited aldehyde oxidase, but a change in the ratio was found at high pH values and in the presence of a competing substrate, N-methylphenanthridinium. This may indicate that a quaternary substrate binds to aldehyde oxidase in two alternative positions.

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