Enzymic oxidation of 3-hydroxyxanthine to 3-hydroxyuric acid

Bergmann, Felix; Levene, Lawrence

doi:10.1016/0005-2744(77)90269-8

Cited by 3 publications

(1 citation statement)

References 11 publications

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“…must be considered for aqueous solutions of xanthine and many related substrates (4)(5)(6)(7). Since most pyridinium and quinolinium cations exist as unique species in the pH region in which the enzyme is stable (up to approximately pH l l ) , it seemed that such heteroaromatic cations could be profitably used for the detailed exploration of the substrate specificity of this enzyme.…”

Section: Introductionmentioning

confidence: 99%

Specificity of xanthine oxidase for nitrogen heteroaromatic cation substrates

Bunting¹,

Laderoute²,

Norris³

1980

Can. J. Biochem.

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A variety of pyridinium, quinolinium, and benzoquinolinium cations have been investigated as potential substrates for milk xanthine oxidase at pH 9.9 and (or) pH 10.6. Steady-state kinetic parameters (kc, Km and (or) kc/Km) have been evaluated for all substrates which are enzymically oxidized. Simple N-alkyl pyridinium cations are neither substrates nor inhibitors, although N-aryl pyridinium cations are slowly oxidized to the 4-pyridinones. N-Methylpyridinium cations bearing 3-CONH2, 3-CONHCH3, 3-COCH3, 3-CO2- or 3-CN substituents are readily oxidized at C-6 and this suggests an important hydrogen-bonding interaction between an enzyme donor and the C-3 carbonyl substituent. A variety of N-methylquinolinium cations bearing C-6 substituents are enzymically oxidized at C-2. Analogous substituent effects on kc/Km for these 6-substituted 1-methylquinolinium cations and the corresponding 1-(substituted phenyl)-pyridinium cations is suggestive of the relative productive binding orientations of these two classes of substrate in the active site. N-Methylbenzoquinolinium and 1,10-phenanthrolinium cations are the best cationic substrates found to date, and suggest a relatively large active-site region for the reducing substrate, and important hydrophobic interactions between enzyme and substrate. The overall enzymic specificity observed for these cationic substrates allows a mapping of the general features of the reducing substrate binding site of this enzyme.

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Section: Introductionmentioning

confidence: 99%

Specificity of xanthine oxidase for nitrogen heteroaromatic cation substrates

Bunting¹,

Laderoute²,

Norris³

1980

Can. J. Biochem.

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Synthesis of 3‐alkyl‐6‐phenyl‐4(3H)‐pteridinones and their 8‐oxides. Potential substrates of xanthine oxidase

Meester¹,

Kraus²,

Plas³

et al. 1987

Journal of Heterocyclic Chem

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Synthetic routes for the preparation of 3‐alkyl‐6‐phenyl‐4(3H)‐pteridinones 6 and their corresponding 8‐oxides 5 (R = CH3, C2H5, (CH2)2CH3, (CH2)3CH3, CH(CH3)C2H5, CH(CH3)2 and CH(C2H5)CH2OCH(OC2H5)2 are described and their reactivities towards xanthine oxidase from Arthrobacter M‐4 are determined. Only the 3‐methyl derivative of 6‐phenyl‐4(3H)‐pteridinone and its 8‐oxide i. e. 6a and 5a are found to be substrates although their reactivities are still very low. Oxidation takes place at C‐2 of the pteridinone nucleus. All the 3‐alkyl derivatives are less tightly bound to the enzyme than 6‐phenyl‐4(3H)‐pteridinone. Introduction of the N‐oxide at N‐8 considerably lowers the binding of the substrates. Inhibition studies have revealed that 3‐methyl‐6‐phenyl‐4(3H)‐pteridinone (6a) is a non‐competitive inhibitor with a Ki‐value of 47 μM and the 3‐ethyl derivative (6b) an uncompetitive one with a Ki‐value of 19.6 μM.

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The oxidation of 7‐(p‐X‐phenyl)pteridin‐4‐ones (X = Me, H, Br, CN, NO₂) with free and immobilized xanthine oxidase

Tramper

Nagel

Plas

et al. 1979

Recl. Trav. Chim. Pays‐Bas

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Abstract. Bovine milk xanthine oxidase was used as a catalyst for the oxidation of various 7-(p-Xphenyl)pteridin-4-ones into 7-(p-X-phenyl)lumazines. On a preparative scale the derivatives with X = Br, CN and NO, were most conveniently oxidized with the free enzyme in a solution continuously fed with concentrated substrate. The lumazines obtained separated during the reaction and were easily isolated in good yield (> 90 %) and high purity by filtration. The compounds with X = H and OMe, on the other hand, were more conveniently oxidized with the immobilized enzyme, i.e. xanthine oxidase adsorbed to 1-octyl-substituted Sepharose 4B. Immobilized xanthine oxidase was used either as a suspension in a stirred batch reactor which was continuously fed with concentrated substrate, or packed in a column through which substrate solution was recirculated. After completion of the reaction the filtrate of the suspension, or the concentrated recirculation solution, respectively, were acidified and the product was collected in good yield (>90%) and high purity by filtration. The rate of oxidation was found to be influenced by the substituent X. The more electron attracting X, by either resonance or induction, the lower the reaction rate. Accordingly, a negative reaction constant p of --0.5 was calculated from the data for the free and immobilized enzyme. The enzyme-substrate complex formation, as reflected in the Michaelis constant K,, is largely determined by the hydrophobicity of the phenyl group.

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Enzymic oxidation of 3-hydroxyxanthine to 3-hydroxyuric acid

Cited by 3 publications

References 11 publications

Specificity of xanthine oxidase for nitrogen heteroaromatic cation substrates

Specificity of xanthine oxidase for nitrogen heteroaromatic cation substrates

Synthesis of 3‐alkyl‐6‐phenyl‐4(3H)‐pteridinones and their 8‐oxides. Potential substrates of xanthine oxidase

The oxidation of 7‐(p‐X‐phenyl)pteridin‐4‐ones (X = Me, H, Br, CN, NO₂) with free and immobilized xanthine oxidase

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Enzymic oxidation of 3-hydroxyxanthine to 3-hydroxyuric acid

Cited by 3 publications

References 11 publications

Specificity of xanthine oxidase for nitrogen heteroaromatic cation substrates

Specificity of xanthine oxidase for nitrogen heteroaromatic cation substrates

Synthesis of 3‐alkyl‐6‐phenyl‐4(3H)‐pteridinones and their 8‐oxides. Potential substrates of xanthine oxidase

The oxidation of 7‐(p‐X‐phenyl)pteridin‐4‐ones (X = Me, H, Br, CN, NO2) with free and immobilized xanthine oxidase

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The oxidation of 7‐(p‐X‐phenyl)pteridin‐4‐ones (X = Me, H, Br, CN, NO₂) with free and immobilized xanthine oxidase