Adenosine urinary excretion

Features of lithium-induced hyperparathyroidism include a) a low urinary calcium excretion and the absence of nephrolithiasis b) normal urinary cyclic adenosine monophosphate excretion and c) normal plasma inorganic phosphate [32]. In lithium-induced hypercalcemia, a higher frequency of conduction defects has been noted [47]. Lithium also inhibits par-... 

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 The (deoxy)ribonucleotide content of the erythrocytes was analyzed by HPLC Ul)- Perchloric acid extracts of freshly withdrawn blood were made according to Cohen et al.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). 

Studies in experimental species demonstrate that methyl donor availability affects the methylation of iAs. In mice exposed to arsenite (As ), depletion of the intracellular pool of 5-adomet by treatment with periodate-oxidized adenosine (PAD), an inhibitor of 5-adomet synthesis (Hoffman 1980), results in reduced urinary excretion of DMA (Marafante and Vahter 1984). Marafante and Vahter (1986) showed that consumption of choline-deficient diet decreased the urinary excretion of DMA and increased tissue As retention in rabbits given 0.4mg arsenate (As )/kg i.v. The same effect of a diet deficient in choline, methionine, and protein was observed in rabbits after administration of 0.4mg As Vkg i.v. (Vahter and Marafante 1987). 

Foscarnet competitively inhibits Na -Pj cotransport in animal and human kidney proximal tubule brush border membrane vesicles, reversibly inhibiting sodium-dependent phosphate transport [48, 49]. Renal cortical Na-K-ATPase and alkaline phosphatase activity are not inhibited by foscarnet, nor is proline, glucose, succinate, or Na" transport [48,49]. Foscarnet induces isolated phosphaturia without hypophosphatemia in thyroparathyroidectomized rats maintained on a low phosphorus diet, without affecting glomerular filtration rate, urinary adenosine 3 5 -cyclic monophosphate (cAMP) activity, or urinary calcium, sodium or potassium excretion [48,50]. Sodium-Pj cotransport in brush border membrane vesicles from human renal cortex was reported to be even more sensitive to inhibition by foscarnet than in rat renal brush border membrane vesicles [49]. 

CM-induces intrarenal hypoxia, possibly related to the hemodynamic changes and/or increased tubular energy expenditure in response to osmotic stress [33]. It has been proposed that increased renal adenosine levels arising from enhanced ATP hydrolysis may be a major contributor to development of acute renal failure after CM apphcation (Figure 1). This is corroborated by the finding that apphcation of CM increases urinary adenosine excretion [44, 45] and the observation that dipyridamol, a nucleoside uptake blocker, magnifies the renal hemodynamic effects of CM [44, 45]. In addition, there are many similarities between... 

Simmonds, H.A., Sahota, A., Potter, C.F., Cameron, J.S. Purine metabolism and immunodeficiency urinary purine excretion as a diagnostic screening test in adenosine deaminase and purine nucleoside phosphorylase deficiency. Clin. Sci. and Molec. Med. 54 579-584 (1978). 

The enzyme 5-phosphoribosyl-l-pyrophosphate (PRPP) synthetase (EC 2.7.6.l) catalyzes the synthesis of PRPP from ribose-5-phosphate (R-5-P) and adenosine 5 triphosphate (ATP) in the presence of magnesium and inorganic phosphate (9-ll). In the present communication we report studies on a mutant superactive PRPP synthetase in the erythrocytes of two brothers with excessive purine production associated with gout and uric acid lithiasis. In these two patients the serum uric acid reached 13.5 and 13.6 mg percent and the urinary 24 hours uric acid excretion 2400 mg and 2250 mg, respectively. All other members of the family examined were clinically and biochemically normal, except for the mother of the patients who had hyperuricosuria, 1100 mg per 24 hours. 

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