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.

Precision-cut Guinea-pig Liver Slices as a Tool for Studying the Toxicity of Volatile Anaesthetics

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 191-199
Author(s):  
Hanan N. Ghantous ◽  
Jeanne Fernando ◽  
Scott E. Morgan ◽  
A. Jay Gandolfi ◽  
Klaus Brandel
Keyword(s):  
Guinea Pig ◽  
Rank Order ◽  
Normal Liver ◽  
Liver Slice ◽  
Volatile Anaesthetics ◽  
Pig Liver ◽  
Liver Slices ◽  
Guinea Pig Liver ◽  
Krebs Henseleit Buffer

Cultured precision-cut liver slices retain normal liver architecture and physiological biochemical functions. Hartley male guinea-pig liver slices have proven to be a good model for studying the biotransformation and toxicity of halothane. This system was used to evaluate the biotransformation and toxicity of different volatile anaesthetics (halothane, enflurane, isoflurane and sevoflurane), and compare their effects to those of new anaesthetics (desflurane). Liver slices (250–300μm thick) were incubated in sealed roller vials, containing Krebs Henseleit buffer at 37°C under 95% O2:5% CO2 atmosphere. Volatile anaesthetics were delivered by volatilisation after pre-incubation for 1 hour to produce a constant concentration in the medium. Production of the metabolites, trifluroacetic acid and fluoride ion, was measured. Intracellular potassium ion content, protein synthesis and secretion were determined as indicators of viability of the slices. The rank order of biotransformation of anaesthetics by the liver slices was halothane >sevoflurane>isoflurane and enflurane>desflurane. The rank order of hepatotoxicity of these anaesthetics was halothane>isoflurane and enflurane>sevoflurane and desflurane. Halothane is the anaesthetic which is metabolised furthest and has the most toxic effect, while desflurane is the least metabolised anaesthetic and has the least toxicity. This in vitro cultured precision-cut liver slice system appears to be suitable for studying the biotransformation of volatile anaesthetics and correlating its role in the resulting toxicity.

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.

scholarly journals Guinea-pig liver tryptophan pyrrolase. Absence of detectable apoenzyme activity and of hormonal induction by cortisol and possible regulation by tryptophan

1974 ◽  
Vol 138 (3) ◽  
pp. 445-451 ◽  
Author(s):  
Abdulla A.-B. Badawy ◽  
Myrddin Evans
Keyword(s):  
Guinea Pig ◽  
Liver Enzyme ◽  
Guinea Pigs ◽  
Actinomycin D ◽  
The Other ◽  
Pig Liver ◽  
Latent Form ◽  
Tryptophan Pyrrolase ◽  
Guinea Pig Liver

1. When assayed in fresh homogenates, guinea-pig liver tryptophan pyrrolase exists only as holoenzyme. It does not respond to agents that activate or inhibit the rat liver enzyme in vitro. Only by aging (for 30min at 5°C) does the guinea-pig enzyme develop a requirement for ascorbate. 2. The guinea-pig liver enzyme is activated by the administration of tryptophan but not cortisol, salicylate, ethanol or 5-aminolaevulinate. 3. The tryptophan enhancement of the guinea-pig liver pyrrolase activity is prevented by 0, 34 and 86% by pretreatment with actinomycin D, cycloheximide or allopurinol respectively. 4. The guinea-pig liver tryptophan pyrrolase is more sensitive to tryptophan administration than is the rat enzyme. On the other hand, the concentrations of tryptophan in sera and livers of guinea pigs are 45–52% less than those in rats. 5. It is suggested that tryptophan may regulate the activity of guinea-pig liver tryptophan pyrrolase by mobilizing a latent form of the enzyme whose primary function is the detoxication of its substrate.

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