Uracil urinary excretion

Bianchini F, Hall J, Donato F, Cadet J (1996) Monitoring urinary excretion of 5-hydroxymethyluracil for assessment of oxidative DNA damage and repair. Biomarkers 1 178-184 Bienvenu C, Wagner JR, Cadet J (1996) Photosensitized oxidation of 5-methyl-2 -deoxycytidine by 2-methyl-1,4-naphthoquinone characterization of 5-(hydroperoxymethyl)-2 -deoxycytidine and stable methyl group oxidation products. J Am Chem Soc 118 11406-11411 Bothe E, Behrens G, Schulte-Frohlinde D (1977) Mechanism of the first order decay of 2-hydroxypro-pyl-2-peroxyl radicals and of O2 formation in aqueous solution. Z Naturforsch 32b 886-889 Bothe E, Deeble DJ, Lemaire DGE, Rashid R, Schuchmann MN, Schuchmann H-P, Schulte-Frohlinde D, Steenken S, von Sonntag C (1990) Pulse-radiolytic studies on the reactions of S04 with uracil derivatives. Radiat Phys Chem 36 149-154... 

On a low protein diet, when the blood ammonia is considerably decreased, the urinary excretion of these compounds is also reduced. Even so some orotic acid and uracil is always found, although uridine may be completely absent from the urine (L6). 

Weissmann et al. (4) have calculated that in man approximately 800 to 1000 mg of uracil are synthesized de novo per day. The normal urinary excretion of orotate is approximately 1.4 mg per day, and that of orotidine, 2.5 mg per day (6). In patients with orotic aciduria due to decreased orotidylate decarboxylase, the excretion of orotate may increase 20-fold (5), although the excretion of orotidine does not necessarily increase. 

Trace amounts of uracil, uridine, thymine, and cytosine may also be found in human urine, along with pseudouridine, 5-methylcytosine, 3-methylcytosine, and 2 -0-methylcytidine (6, 7). Immediately following X-irradiation the urinary excretion of deoxycytidine and thymidine is markedly increased (8). 

An earlier trial of administration of dCyd orally and intravenously did not result in a detectable serum level of dCyd, whereas the urinary excretion of uracil increased markedly. This time, during combined administration of dCyd and THU a considerable amount of dCyd was found in the plasma and in the urine and uracil excretion did not change (Fig.l). This reflects an effective inhibition of deoxycytidine deaminase by THU and strongly suggests that the compound is administered under conditions which make adequate uptake by cells possible. The low dCyd plasma level during subcutaneous administration (see Fig.l) is due to the time interval between the end of the overnight infusion and the blood sampling. 

G. Berglimd, J. Greter, S. Lindstedt, G. Steen, J. Walden-strdm and U. Wass, Urinary excretion of thymine and uracil in a two-year-old child with a malignant tumor of the brain, Clin. Chem. 25 1325-1328 (1979). 

Fig.1 Urinary output of uric acid, hypoxanthine+xanthine, uracil and CAMP in 18 normal newborns on their first and fourth day of life. Mean and SD-range of the values. The 24-h. urinary excretions of the same substances measured in 4 newborns during and after E.T. are plotted. Numbers above the circles refer to the patient s number.

Manzke, H., Spreter v. Kreudenstein, P., Dorner, K., and Kruse, K., 1980, Quantitative measurements of the urinary excretion of creatinine, uric acid, hypoxanthine and xanthine, uracil, cyclic AMP and cyclic GMP in healthy newborn infants, Eur. J.Pediatr. 133 157... 

From metabolic studies, an isotopic caffeine breath test has been developed that detects impaired liver function using the quantitative formation of labeled carbon dioxide as an index. From the urinary excretion of an acetylated uracil metabolite, human acet-ylator phenotype can be easily identified and the analysis of the ratio of the urinary concentrations of other metabolites represents a sensitive test to determine the hepatic enzymatic activities of xanthine oxidase and microsomal 3-methyl demethylation, 7-methyl demethylation, and 8-hydroxylation. Quantitative analyses of paraxanthine urinary metabolites may be used as a biomarker of caffeine intake. Fecal excretion is a minor elimination route, with recovery of only 2-5% of the ingested dose. 

Certain metabolites of the pyrimidine pathway are excreted in excess of the normal in inherited metabolic disorders of the urea cycle. They include orotic acid, uridine, and uracil. Of these substances, only uracil is a normal constituent of urine, the other two either being absent or present in very small amount. They are readily detected qualitatively as dark bands at the appropriate Rf values when a paper chromatogram of the urine is examined under ultraviolet light. They may be estimated by an ion exchange method similar to that for urinary pseudouridine (R13). 

The method used for the collection of luine to detect urinary solids is particularly sensitive to a variety of artifacts and variations in treatment (Cohen et al. 2007). Most of all, it is essential that the animals not be fasted or go without water during the period of collection of urine. Since the excretion of the substances that are included in formation of the urinary solids is dependent on their consmnption, fasting the animals changes the urine composition considerably and can lead to a condition in which the solids are no longer formed. Fiulhermore, urinary solids can be rapidly excreted in the mine and are not retained so if they are not being constantly formed anew, they will not be detected. This includes urinary tract calculi. Some calculi will be small enough that they will be excreted in the urine, or dissolve with the lowering of the concentration of the solute itself. Furthermore, many of these calculi are actually quite soluble in urine, such as uracil, and rapidly solubilize in the urine. 

Ornithine carbamoyltransferase (ornithine transcar-bamylase) (EC 2.1.3.3). Gross elevation of blood ammonia. Elevated glutamine in plasma and cerebrospinal fluid. Urea excretion low. Urinary orotic add increased. Uracil and uridine in urine. Gene for enzyme X-linked. Condition severe in boys (0-0.2% of normal enzyme activity in liver), who die in postnatal period (some cases of late onset have been reported). Girls have 5-10% normal liver enzyme activity. Some girls have died in late infancy or childhood, and others have survived with restricted protein intake. Abnormal EEC, mental retardation, brain atrophy and hepatomegaly. 

Elevated concentrations of orotic acid and uracil may be found in the urine of heterozygote carriers for urea cycle disorders, most commonly ornithine carbamoyltransferase (OCT) deficiency. This is due to the increased flux through the pyrimidine pathway which occurs, especially where the relevant enzymes are expressed only in liver tissue, as is the case when urea cycle enzymes are defective. A protein load was used previously to stress this route and the elevation in orotic acid excretion used as a diagnostic marker. However, the test frequently failed to detect known carriers. The al-lopurinol loading test (measurement of the increment in urinary orotic acid and orotidine in three separate 8 hour urine collections over the 24 hours following a 300 mg allopurinol tablet) is the most reliable test so far for carrier detection for such disorders [17]. 

---