The first dissociation constant of uric acid

Smith, Robert C.; Gore, J.; McKee, Michael L.; Hargis, Howard

doi:10.1016/0026-265x(88)90010-0

Cited by 22 publications

(19 citation statements)

References 15 publications

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“…Indeed, UA and DiMUA exist mainly as their enolate forms releasing H ϩ at N3 or N9 under neutral conditions with pK a values of 5.3-6.2. [16][17][18] If NO-UA and NO-DiMUA exist in their enolate forms at pH 7.4 and if their decomposition reactions are base-catalyzed hydrolysis, the reactions would be slower than those in the neutral keto forms. On the other hand, NO-TriMUA cannot possess an enolate form, since NO-TriMUA has no hydrogen atom to release as H ϩ on its structure.…”

Section: Discussionmentioning

confidence: 99%

Nitrosation of N-Methyl Derivatives of Uric Acid and Their Transnitrosation Ability to N-Acetylcysteine

Suzuki

Yamamoto

Pfleiderer

2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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Nitric oxide (NO) is an inorganic gas synthesized from L-arginine by the enzyme nitric oxide synthase in various types of cells.1) NO is involved in numerous biological functions, including vasodilation, neurotransmission, and inflammation.2) NO is a radical, demonstrating both cytotoxic and cytoprotective properties.3) Although the reactivity of NO per se is relatively low, NO is converted to a reactive nitrosating reagent, dinitrogen trioxide (N 2 O 3 ), in the presence of O 2 . 4)N 2 O 3 can react with amino and imino groups in various biological molecules resulting in corresponding N-nitroso compounds, many of which are mutagenic and carcinogenic since they can act as alkylation reagents to form DNA-adducts. 5)N 2 O 3 can also react with thiols such as free cysteine and cysteine residues of peptides or proteins resulting in S-nitroso compounds, nitrosothiols. 6,7) Nitrosothiols are relatively stable and can release NO when they encounter transition metals or other reducing agents.8-10) Therefore, it can be seen that thiols act as an NO buffering system, controlling the intra-and extracellular activities of NO. We have recently reported the identification and characterization of a reaction product of uric acid (UA) with NO. 11,12) When UA was treated with NO gas in a neutral solution under aerobic conditions, UA was consumed, yielding an unknown product. The product was identified as a nitrosated UA (NO-UA) from mass spectrometric data, although the position of the nitroso group on the molecule was not determined. NO-UA was unstable and decomposed with a half-life of 2.2 min at pH 7.4 and 37°C. The incubation of NO-UA with glutathione resulted in the formation of S-nitrosoglutathione. NO-UA was also formed in the reaction with an NO donor, diethylamine NONOate (DEA-NO). NO-UA was detected in human serum and urine by in vitro treatment with DEA-NO. In the reactions of glutathione and N-acetycysteine (AcCys) with DEA-NO, the addition of UA caused increases in the yields of S-nitrosoglutathione and N-acety-S-nitrosocysteine (NOAcCys), respectively. These results indicate that UA can readily react with NO, thereby generating a nitroso derivative which, in turn, can effectively transfer the nitroso group to thiols. Several UA derivatives methylated on nitrogen atoms exist in nature. 1,3-Dimethyluric acid (DiMUA, Fig. 1) is a metabolite of 1,3-dimethylxanthine (known as theophylline) formed by the C-8 hydroxylation. 1,3,7-Trimethyluric acid (TriMUA, Fig. 1) is a metabolite of 1,3,7-trimethylxanthine (well known as caffeine) formed by the C-8 hydroxylation. 1,3,7,9-Tetramethyluric acid (TetraMUA, Fig. 1), known as theacrine, is a major purine alkaloid in the leaves of an unusual Chinese tea kucha. 13) In the present study, we investigated the reactions of DiMUA, TriMUA, and TetraMUA with DEA-NO and the effects of these compounds on the nitrosation of AcCys by DEA-NO. ResultsDiMUA (300 mM) was incubated with DEA-NO (300 mM) in potassium phosphate buffer (100 mM) at pH 7.4 and 37°C, and the reaction was monitored by r...

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Section: Discussionmentioning

confidence: 99%

Nitrosation of N-Methyl Derivatives of Uric Acid and Their Transnitrosation Ability to N-Acetylcysteine

Suzuki

Yamamoto

Pfleiderer

2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…UV spectrophotometric (33) and 13 C NMR studies (2) have previously shown that these are the predominant tautomeric forms in acidic, neutral, and alkaline solution, respectively. Previous theoretical studies have also shown that the N3-deprotonated monoanion is the most stable urate tautomer in the gas phase (2,37). Geometry optimizations at the MP2/6-311G(d,p) level showed that the planar forms are the energy minima for uric acid and urate monoanion; for urate dianion the nonplanar conformation is 0.87 kcal/mol lower in energy than the planar conformation.…”

Section: Figmentioning

confidence: 90%

Theoretical Study of Intermediates in the Urate Oxidase Reaction

Kahn

1999

Bioorganic Chemistry

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“…18 Xanthosine and its monophosphate have slightly lower pK a1 (HN3) values (5.7 18 A recent paper also corroborates the order of deprotonation in xanthine (N3 > N7) using Raman spectra. 15 9-Methyluric acid (1b) has pK a1 (HN3) 5.10 AE 0.05 16 and 5.04, 19 and pK a2 (HN7) 11.46 AE 0.1. 16 Pfleiderer has also found pK a1 (HN3) 5.27 AE 0.04, and pK a2 (HN9) 10.90 AE 0.1 for uric acid itself.…”

Section: Introductionmentioning

confidence: 99%

“…17 Hargis et al have found the value 5.53 as the first dissociation constant of uric acid. 19 The pK a for protonated guanosine (HN7 + ) has been reported to be 1.9, 23 and 2.2, 18 for protonated hypoxanthine 1.8, 23 for inosine 1.0. 18 The pK a for the dissociation of N(7)-protonated 9-methylxanthine is 2.0, 21 for xanthine this pK a is 0.8, 18 for xanthosine 1.1.…”

Section: Introductionmentioning

confidence: 99%