Adenine urinary excretion

Normally dietary NA is hydrolyzed by pancreatic ribonucleases and absorbed in the small intestine. Guanine and adenine are metabolized further to uric acid before urinary excretion (2). Increased consumption of NA increased the uric acid levels above the urinary excretion rate, resulting in an increased plasma uric acid level. Uric acid has a pKa near 5.4. In the acidic urine, as much as half of the excreted compound may be in the form of the undissociated acid, which has a low solubility... 

E. The patient has demonstrated a deficiency in riboflavin (urinary excretion of less than 30 pg/mg creatinine is considered clinically deficient). Riboflavin is a component of the cofactor FAD (flavin adenine dinucleotide), which is required for the conversion of succinate to fumarate by succinate dehydrogenase. 

X Uric acid contains two rings and is similar to the purines adenine and V y guanine (adenine is shown in Fig. 5.25). In fact, it is the urinary excretion product formed from the oxidation of these two purine bases. It is not very soluble in water, particularly if the pH is near the pK of its acidic OH group. If present in excess amounts, Na+ urate tends to precipitate in joints, causing the severe pain of gout experienced by Ms. Topaigne. 

The increased plasma kynuremne pool and the induced xanthurenic acid urinary excretion have several implications in the assessment of diazinon noncholinergic toxicity. An increase in xanthurenic acid formation may alter glucose metabolism. Xanthurenic acid has been reported to form a complex with insulin and damage pancreatic P cells. Elevated plasma kynurenin may alter kynurenin transport into the brain. Since more than 40% of brain kynurenin originates from the systemic circulation, cerebral biosynthesis of neuroactive kynurenin metabolites such as quinolinic acid and kynurenic acid may change. Finally, the availability of L-iryptophan for other L-lryptophan-dependent processes may be reduced. Tryptophan is the metabolic precursor for. serotonin and nicotinic adenine dinucleotidc. Diabetes, bladder cancer, and neurological disorders may be the toxic consequences of diazinon-altered L-tryptophan metaboli.sm (Seifert and Pewnim, 1992 Pewnim and Seifert, 1993). 

Table lO-II gives the results of one study of urinary excretion in man of allantoin and of purines other than uric acid (4 ). In addition, 1-methyl-adenine, iS -methyladenine, iVMimethylguanine, iV -methyladenosine, adenosine, and 1-methylguanosine have also been reported to be in human urine (43). The methylated purines are believed to be derived mainly from the catabolism of transfer RNA. 

In subject 2 the urinary excretion of adenine increased from 16.4(+2.85)umol/24h during the first week to 175 (+68.8)umol/24h during the administration of adenine corresponding to 3.5% of the increment of purine excretion. 

At the present time, we just report some experimental results of a study on the mechanism of action of allopurinol (U-hydroxy-pyrazolo (3, -d ) pyrimidine) and thiopurinol k thiopyrazolo (3, d) pyrimidine) on de novo biosynthesis of uric acid. In this present work, we have compared effect of alio and thiopurinol on oxypurine (xanthine and hypoxanthine) urinary excretion with their rate of synthesis of ribonucleotides in vitro by erythrocyte hemolysate in some particular enzymatic deficiencies (hypoxanthine-guanine phosphoribosyltransferase HGPRT, adenine phosphoribosyl-transferase APRT and xanthinuria). 

His urinary excretion was normal for adenine (1,73 mg/ day) and for guanine (0,93 mg/day). We dit not find any measurable amount of 8 hydroxy-7 methyl guanine in daily urine but a concomitant increase of 7"methyl guanine (9 10 mg/day control 6,9 mg/day). SKUPP and AYVAZIAN (1969) have demonstrated that 8 hydroxy-7 methyl guanine is the product of oxidation ofT-methyl guanine but only by human liver xanthine oxidase. This xanthinuric man has a family, but up to now we have only seen one of his sisters who also has xanthinuria. 

W.J. Suling, L.S. Rice, W.M. Shannon, Effects of 2 -deoxycoformycin and erythro-9-(2-hydroxy-3-nonyl)adenine on plasma levels and urinary excretion of 9-P-D-arabino-furanosyladenine in the mouse, Cancer Treat. Rep. 62 369 (1978). 

Biochemical status estimates are generally based upon urinary excretion or measurements of erythrocyte glutathione reductase (NADPH oxidized glutathione oxidoreductase EC 1.6.4.2) and its reactivation with flavin adenine dinucleotide (FAD) in red cell lysates. Other biochemical indices, such as plasma or red cell flavin concentrations, have been less widely used, but their potential is increasing with the advent of new assay techniques such as capillary electrophoresis with highly sensitive laser-induced fluorescence detection. Fvmctional indices... 

Examination of the urine of subjects receiving EATDA showed that several, if not all, of the urinary purines were excreted in increased amounts. There was, furthermore, no change in the mode of excretion of urates or in the proportion disposed of extrarenally (S12). The suggestion has been made (K18) that the fundamental mechanism of action of these compounds is the blocking of the incorporation of newly synthesized adenine into polynucleotides and/or coenzymes, with the production of an undefined deficiency state. This block could stimulate a compensatory increase in purine biosynthesis. The excess purines would not be utilizable and, therefore, would be excreted from the cells, and the normal degradation by enzymes would convert this material to uric acid. 

Brown, D.R., Donavan, E.F., Tsang, R.C., Bobik, C.M., Chen, I.-W., and Johnson, J.R., 1978 Urinary phosphate and cyclic AMP excretion following citrate-induced hypocalcemic stimulation of the neonatal parathyroid glands, J.Pediatr. 93 842 Kreuger, A., 1976 Adenine metabolism during and after exchange transfusions in newborn infants with CPD-Adenine blood. Transfusion 16 249... 

After normalization of nitrogen and acid-base balance adenine was re-administered at a dose of 500 mg/day (40 mg/kg/day), associated with allopurinol (150 and later 200 mg/day). This time the efficacy of the treatment was very poor the mother noticed the reappearence and the persistence of the orange flecks on the underclothes blood UA level rosed to 13.5 mg% in January 1973 and to 14.5 mg% in april 1973, when urinary UA excretion was respectively 900 and 710 mg/day. This was an unexpected finding, since it must almost be observed the UA level reducing effect of allopurinol. No interference of adenine on allopurinol activity has been demonstrated It is admissible a reduced intake of allopurinol due to the vomiting (adenine was administered as a powder mixed with the foods, while allopurinol was taken as a crumbled tablet), but it remains to explain the different activity of adenine, unless it was believed to be dose-related. 

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