Uric acid spectrum

The term gout describes a disease spectrum including hyperuricemia, recurrent attacks of acute arthritis associated with monosodium urate crystals in leukocytes found in synovial fluid, deposits of monosodium urate crystals in tissues (tophi), interstitial renal disease, and uric acid nephrolithiasis. 

Enzyme catalysis can be employed to detect concentrations of metabolites such as blood sugar, urea, uric acid or ATP. The metabolite is often best reacted with a co-enzyme such as NADPH or pyridoxal phosphate which changes its UV-vis absorption spectrum upon reaction. 

Losartan was shown to increase uric acid excretion by inhibiting its tubular reabsorption. This effect does not lie within the spectrum of the blockade of AT, receptors, but rather is a genuine action of the drug on renal tubuli. Losartan was also shown to decrease ocular pressure in normotensive as well as in hypertensive patients with or without glaucoma. Losartan and eprosartan also reduce central sympathetic tone. A metabolite of losartan, EXP-3179 (Fig. 5.8), does not block AT, receptors but may inhibit the atherosclerotic process by suppressing intercellular cell adhesion molecules (ICAM-1), cyclooxygenase-2 (COX-2) and thrombox-ane-A2 (TXA-2). These effects of losartan may lead to potential indications other than blood pressure reduction in hypertensive patients [7]. 

J. G. Puig, A. D. Michan, M. L. Jimenez, et al. Clinical spectrum and uric acid metabolism. Archives of Internal Medicine 151, 726 (1991). 

On average, only 30% to 60% of patients are able to tolerate oral CAI therapy for prolonged periods. Intolerance to CAI therapy results most commonly from a symptom complex attributable to systemic acidosis and including malaise, fatigue, anorexia, nausea, weight loss, altered taste, depression, and decreased libido. Other adverse effects include renal calculi, increased uric acid, blood dyscrasias, diuresis, and myopia. Elderly patients do not tolerate CAIs as well as younger patients. The three available CAIs produce the same spectrum of adverse effects however, the drugs differ in the frequency and severity of the adverse effects listed. Acetazolamide (standard or sustained-release capsules) and methazolamide are considered the best-tolerated CAIs. 

A large number of isobaric compounds, especially those of uric acid, was studied. The spectrum of this compound is distinguished considerably from those of its isobars. Using FI with their instrument, they detected small quantities of caffeine in complex samples (urine). Maquestiau et al. [245] also demonstrated the same compound in tea samples with the same method, but they used Cl conditions to produce protonated molecules. 

Figure 2 shows the three successive derivatives of a normal spectrum of uric acid solution. The first derivative corresponds to the slope of the normal spectrum, with maxima corresponding to the increase of the absorbance with wavelength, and minima appearing after the maxima of the usual spectrum. On the other hand, the curve goes through a zero value, which corresponds to the maxima of the usual spectrum. 

Figure 2. Spectrum of uric acid, and derivative spectra (first, second and third) calculated with several differentiation steps (2, 5, 10, 20 and 30 nm). For example d2s10 is the second derivative spectrum fora diffferentiation step of 10 nm.

Uric acid ribonucleoside (13) has been isolated from beef blood and liver. It is hydrolyzed in acid to uric acid and n-ribose, and a comparison of its ultraviolet spectrum with those of the four monomethyl-uric acids indicate that the D-ribose moiety is attached to the 9-nitrogen atom. Although it is reasonable to assume that the D-ribose moiety is in the... 

Trihydroxypurine 2,6,8-Trioxopurine Uric acid. Used in organic synthesis. Solid d 1.89 Xm = 286 nm (MeOH) poorly soluble in H2O, organic solvents. Burlington Biomedical ICI Spec. Spectrum Chem. Manufacturing. 

Xanthine oxidase (EC 1.2.3.2) catalyzes the formation of uric acid, an end-product of purine catabolism. The mammalian enzyme is a metalloflavoprotein composed of two subunits containing molybdenum, FAD and Fe/S clusters as prosthetic groups in a ratio of 1 1 4 per subunit (1). Besides its endogenous metabolic function, xanthine oxidase is also active toward a wide spectrum of oxidizable xenobiotic substrates. Although some cestodes and trematodes produce trace amounts of uric acid (16), the presence of xanthine oxidase activity in these organisms has not been demonstrated. Xanthine oxidase was found in the cytosolic fractions of the nematodes Ancylostoma ceylanicum and Nippostrongylus brasiliensis (17), but its activity toward xenobiotic substrates was not tested. 

Figure 24. Spectrum of 1.0 mM uric acid electrolyzing at 0.65 V vs. SCE in 0.5 M NaCl-f 0.005 M Na2HP04, pH 7.5, at a reticulated vitreous carbon electrode in a thin-layer cell. Curve (1) is the spectrum of uric acid before electrolysis. Curve (2) is the spectrum of the uv-absorbing intermediate species. Repetitive sweeps of 19 s are shown.

The product of nucleophilic attack of water on the diimine primary product of electrochemical oxidation of uric acids is an imine-alcohol (see Figure 25). This species is characterized in the case of uric acid in terms of its reduction peak lie observed under cyclic voltammetric conditions and its uv absorption spectrum under thin-layer spectroelectrochemical conditions. Reduction peak lie niay be observed on cyclic voltammetry of all uric acid derivatives. The general reaction involved in forming the imine-alcohol intermediate from neutral or anionic diimines in the case of the group I uric acids is shown in Figure 25. In the case of the positively charged diimines formed upon oxidation of the group II uric acids, the reaction scheme is illustrated in Eq. (17). That... 

The enzymic oxidation of uric acids with peroxidase (type VIII from horseradish peroxidase) has recently been studied and critically compared to the electrochemical oxidation. Peroxidase was studied because this enzyme will oxidize not only uric acid but also most of its N-methyl derivatives. Typical spectra of uric acid obtaine d during the peroxidase-catalyzed oxidation of uric acid are shown in Figure 27. Curve 1 is the spectrum of uric acid. Addition of hydrogen peroxide and peroxidase causes the initial rapid decrease of the spectrum because of dilution. However, it is quite clear from Figure 27... 

Figure 27. Spectrum of 200 fiM uric acid undergoing oxidation in the presence of 200 tiM H2O2 and 0.7 /iM peroxidase in 0.5 M NaCl puls 5 mM Na2HP04, pH 7.5. Curve...

Figure 13.15 shows the spectrum of uric acid for reference and the lower curve is that of a kidney stone which is seen to be mic acid by comparison with the reference spectrum. This application of the KBr technique has been applied in clinical situations. 

The feasibility of on-line electrochemistry mass spectrometry in the study of electrode processes has recently been demonstrated by Heitbaum et al. . We have tested the potential of on-line mass spectrometry in the study of redox reactivity of biological compounds with uric acid as a probe. Electrochemical oxidation of uric acid has been studied extensively . The scheme in Figure 6 shows the electrochemical oxidation pathway of uric acid and indicates intermediates and products which were identified by on-line electrochemistry thermospray mass spectrometry (EC/TSP/MS/MS) . In our studies, tandem mass spectrometry (MS/MS) was used to obtain structurally informative fragmentation patterns (daughter spectra) of standards for comparison to the mass spectra of intermediates and products obtained by EC/TSP/MS/MS. This, for example, allowed identification of allantoin through its characteristic daughter spectrum. It also allowed confirmation of the structural features of the intermediate, bicyclic carboxylic acid, which apparently forms from the imine alcohol in the oxidation of uric acid. The intermediates and products which were identified in this way are indicated in the scheme, and mass spectral results are summarized in Table 1. 

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