Purines urinary excretion

Ldfroth, G., S. Osterman-Golkar, and R. Wennerberg. Urinary excretion of methylated purines following inhalation of dimethyl sulphate. Experientia 30 641-642, 1974. 

However, creatinine and purine derivatives are very important in the field of animal nutrition because measurements of urinary excretion of these compounds have been proposed as an internal marker for microbial protein synthesis. 

Purines are metabolized in a series of reactions involving hypoxanthine, xanthine, uric acid, and allantoin as end products that are subsequently excreted in urine. Fig. 3 shows the metabolic pathways for xanthine. Measurement of urinary excretion of purine metabolites, primarily allantoin or, additionally, uric acid, xanthine, and hypoxanthine, has been proposed as a marker for microbial... 

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. 

Several examples of prodrugs are found in the purine and pyrimidine analogs that substitute for natural nucleotides and inhibit nucleic acid formation. For example, 5-fluorouracil is essentially harmless to mammalian host and tumor cells. Upon administration, the drug is subject to one of two opposingmetabolicfates (10). Inactivation and elimination are accomplished by catabolism (about 80% of the dose) and by urinary excretion of unchanged drug... 

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. 

Creatinine and purine derivatives—allantoin, uric acid, hypoxanthine, and xanthine present in biological samples— are important analytes for diagnoses of certain types of metabolic diseases and can serve as markers for these processes. Analyses for such substances are cmcial for diagnosis and the monitoring of renal diseases, metabolic disorders, and various types of tumorigenic activity. On the contrary, these compounds are very important in the field of animal nutrition, because the measurement of their urinary excretion is being used as an internal marker for microbial protein synthesis. 

Uric acid and xanthines are markers for metabolic disorders such as gout, Lesch—Nyman syndrome, and xanthinuria. Measurements of urinary excretion of purine metabolites, among them uric acid and xanthine, have been proposed as a marker for microbial protein synthesis. Their simultaneous determination is useful for diagnosis and treatment of hyperuricemia. In addition to xanthine and hypoxanthine, notable members of the xanthine class include caffeine, theophylhne, and theobromine. ... 

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. 

At regular intervals the immune status of the patient was assessed as well as the serum content and the urinary excretion of purine- and pyrimidine metabolites according to methods described in detail previously (6,8,10). The (deoxy)ribonucleotide content of the erythrocytes was analyzed by HPLC Ul)- Perchloric acid extracts of freshly withdrawn blood were made according to Cohen et al. (2) with minor modifications. In order to analyze deoxyribo-nucleotides the neutralized perchloric acid extracts were treated with sodium periodate according to Garret and Santi (12). 2,3 Di-phosphoglycerate (2,3-DPG) in the erythrocytes was determined as previously described (13). Ecto-5 -nucleotidase on intact lymphocytes was determined as described(14). Adenosine deaminase activity of the lymphocytes was determined essentially according to van Laar-hoven et al. (15). 

The number of inherited defects of the pyrimidine metabolism described so far is small, compared to that of the purine metabolism. Combined deficiency of orotate phosphoribosyltransferase (OPRT) (EC 2.4.2.10) and orotidine 5 -monophosphate decarboxylase (ODC) (EC 4.1.1.23), designated as type I hereditary orotic aciduria, presents with characteristic clinical features such as hypochromic anemia with a megaloblastic bone marrow and crystalluria. Only six patients have been described and, as far as we know, new cases have not been discovered recently. ODC deficiency with similar clinical phenomena and leading to increased urinary excretion of orotate and orotidine has been detected in only one patient (1). A third defect, a deficiency of pyrimidine 5 -nucleotidase (Py-5NX (EC 3.1.3.5.) in erythrocytes, is associated with chronic hemolytic anemia and prominent basophylic stippling of the erythrocytes due to accumulated pyrimidine nucleotides. An increasing number of patients have been reported, their detection being facilitated by the typical phenomena. We do not know whether the urinary pyrimidine profile in this condition is abnormal. 

J.W. Stoop and S.K. Wadman, Urinary excretion of orotic acid, orotidine and other pyrimidines in a patient with purine nucleoside phosphorylase deficiency, Clin. Chim. Acta, 93 ... 

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. 

Fig. 1 shows the urinary excretion of allopurinol and its metabolites in subject 1(oxipurinol-7-riboside not determined). The administration of hypoxanthine as well as the other purines tested(table 2) caused a marked decrease of the excretion of allopurinol-1-riboside. This is most likely due to the increased formation of hypoxanthine (table 1) which can competitively inhibit the conversion of allopurinol by PNP or HGPRT, allopurinol-1-riboside... 

Table 2. Reduction of the urinary excretion of allopurinol-1-riboside by dietary purines.

Table 3. Reduction of urinary excretion of orotic acid and orotidine by dietary purines.

During recent years WASLIEN et al. as well as our group have studied the influence of dietary purines on plasma levels and urinary excretion of uric acid in man, using modern feeding techniques. In these experiments defined quantities of RNA and DNA were added to an isocaloric, purine free formula diet. [For a review see ZOLLNER et al., 1972]. 

Before describing observations on HGPRTase deficient patients, it is necessary to consider the effect of progressive glomerular insufficiency upon the urinary excretion of urate. Our observations of the 2M- hour urinary excretion of urate on a purine free diet in patients with a wide range of glomerular filtration rates has shown that the urinary urate falls steadily with progressive reduction in the creatinine clearance (Observation 1). 

Xanthinuria is characterized by a large urinary excretion of oxypurine (xanthine + hypoxanthine) which replaces uric acid at the end product of purine metabolism. Patients with xanthinuria are very deficient in xanthine oxidase activity. This rare metabolic disorder may be of interest for both information ... 

Urinary Excretion of Methylated Purines in Man and in the Rat After the Administration of Theophylline... 

Although the propositus was noted to be hyperuricemic he exhibited a normal urinary excretion of uric acid on a purine free diet as well as a normal rate of purine biosynthesis novo. 

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