Uric acid Methyl

Fig. 11. Mechanism for formation of parabanic acids from the methylated uric acid-4,5-diol derived from theobromine (3,7-dimethylxanthine) and caffeine (1,3,7-trimethylxan-thine). Molar amounts of products are those formed in 1 M HOAc...

In the case of the methylated xanthines, particularly theophylline, theobromine and caffeine, the preponderance of data on the metabolism of these compounds in man suggests that a methylated uric acid is the principal product. However, the data presented earlier proposes at best a 77 per cent accounting of the methylated xanthine administered. The question can be raised as to whether the final products observed upon electrochemical oxidation of these compounds aids these studies. Very recently studies of metabolism of caffeine have revealed that 3,6,8-trimethylallantoin is a metabolite of caffeine 48>. This methylated allantoin is, of course, a major product observed electrochemically. The mechanism developed for the electrochemical oxidation seems to nicely rationalize the observed products and electrochemical behavior. The mechanism of biological oxidation could well be very similar, although insufficient work has yet been performed to come to any definite conclusions. There is however, one major difference between the electrochemical and biological reactions which is concerned with the fact that in the former situation no demethylation occurs whereas in the latter systems considerable demethylation appears to take place. 

The electrochemical oxidation of several N-methylated uric acids,405 406 as well as application of thin-layer, spectroelectrochemical, and GLC-MS techniques,407 supported the sequence of the reaction steps shown in Eq, (137). 

Strange to state, the methylated uric acids, when reduced, do yield purons which (excepting tetramethylpuron) can be molecularly rearranged into isomeric isopurons, but the corresponding hydrated uric acids are not produced (Tafel2). 

Methyl Uric Acids, Fischer.— Fischer found two important facts in regard to the methyl uric acids, (a) There is a tetra-methyl uric... 

He found that one of these mono-methyl uric acids yielded methyl alloxan and urea, whereas the other yielded methyl urea and alloxan as indicated by the dotted lines. Therefore uric acid is a di-ureid of an acid as represented below, the ureid being formed as follows ... 

Methyl-xanthine to 1-methyl-uric acid with xanthine oxidase... 

Caffeine (trimethylxanthine), which occurs in both beverages, is similar in structure to xanthine, the immediate precursor of uric acid. Some caffeine molecules are excreted as methyl uric acid, a molecule with solubility properties similar to those of uric acid. Recall that gout is caused by the precipitation of uric acid in the joints. 

Figure 26. Proposed primary electrode reactions for the peak electrochemical oxidation of N-methylated uric acids. The cyclic voltammograms are, from top to bottom, uric acid, 1,3,7-trimethyl uric acid and, 1,3,7,9-tetramethyl uric acid in phosphate buffer, pH 7, at a RPGE at 200 mVs ...

That the imine-alcohol species is the uv-absorbing intermediate is also supported by thin-layer spectroelectrochemical studies of N-methylated uric acids. For example, uric acid and its 1- and 7-methyl derivatives upon... 

Methyl uric acid 3-Methyl uric acid 7-Methyl uric acid 9-Methyl uric acid 1,3-Dimethyl uric acid... 

Paul and Avi-Dor " found that 1-methyl uric acid is oxidized in the presence of horseradish peroxidase and H2O2. This reaction is most rapid when the uric acid molecule is uncharged. According to these workers the primary oxidation product obtained at pH 3-5 could be reversibly transformed into two other spectrophotometrically active forms by changing the pH to >6 or >1. Depending on the pH, the primary oxidation product was proposed to undergo a nonenzymic decomposition to allantoin (pH 3-6) or alloxan (pH[Pg.181]

The reaction schemes shown in Eq. (19) and Figure 29 were thrown into some doubt when Howell and Wyngaarden found that 7-methyl (21) and 9-methyl uric acid (22) were oxidized in the presence of methemoglobin (a hemeprotein or peroxidase enzyme)-H202 or horseradish peroxidase-H202 but that 1,3,7,9-tetramethyl uric acid (23) was not. These workers thus... 

Fischer now showed that hydroxycaffeine (see p. 829) is identical with tri-methyluric acid and is easily produced from trimethylpseudouric acid and by methylating uric acid. He now revised his formulae to the following ... 

Baumann TW, Oechslin M, Wanner H (1976) Caffeine and methylated uric acids chemical patterns during vegetative development of Coffea liberica. Biochem Physiol Pflanzen 170 217-225... 

There are two methylated uric acids which are considered by Wanner et aL (1975) to be the first products of caffeine degradation. They are testing that hypothesis. This is a particularly attractive hypothesis since the two isolated methylated uric acids were not detected before in any Coffea species. These were 2-methoxy-l,9-dimethyl-7,9-dihydro-l//-pur-... 

The Rapid type 2 signal is given by xanthine, usually along with the type 1 signal (Bray and Vanngard, 1969). Product molecules such as uric acid and 1-methyl uric acid are also capable of inducing type 2 signals (Bray et al, 1978) (see also Section 7.5). 

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