Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A method is presented for the two-dimensional thin-layer chromatographic screening of purines, pyrimidines and their nucleosides in the urine. Prior to chromatography, isolation of these substances from the urine is performed by anion-exchange column chromatography. Purines and pyramidines are quantitatively eluted with formic acid 0.01 M and 4 M respectively. The results of recovery and stability experiments are given. Normal excretory patterns are presented. Also results in patients with various diseases are shown: ornithine transcarbamylase deficiency, adenosine deaminase deficiency, purine nucleoside phosphorylase deficiency, adenine phosphoribosyltransferase deficiency, xanthine oxidase deficiency and hypoxanthine-guanine phosphoribosyltransferase deficiency. Finally the pattern of a patient on treatment with allopurinol is given.
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PMID:Two-dimensional thin-layer chromatography for the screening of disorders of purine and pyrimidine metabolism. 9 7

The uptake of purine nucleosides (guanosine and hypoxanthine) and bases (guanine, hypoxanthine and adenine) and their incorporation into nucleotides were studied in enterocytes isolated from fed and 3-day fasted guinea pig jejunum. Both total uptake and synthesis of nucleotides were greater for these purines in the fasted, as compared to the fed state for the first 5 min, when the initial substrate concentration in the medium was 10 microM. Increased uptake did not result from a change in the relative distribution of synthesized nucleotides between the fed and fasted states. Reduced catabolism was observed in the medium by enterocytes from fasted as compared to fed animals after 1 min of incubation with both inosine and guanosine. Preincubation of enterocytes with allopurinol (a xanthine oxidase inhibitor) decreased total uptake but increased the formation of IMP from hypoxanthine. Xanthine oxidase activity measured in mucosa from fasted guinea pigs was lower than that from fed animals (6.29 vs. 9.30 nmol/min per mg protein, respectively). However, activities of the salvage enzymes adenine phosphoribosyltransferase and hypoxanthine-guanine phosphoribosyltransferase were not significantly different between the fed and fasted states. These data show that allopurinol treatment, and mucosal atrophy resulting from fasting, decrease xanthine oxidase activity and increase nucleotide synthesis from exogenous substrates in enterocytes from the guinea-pig small intestine, suggesting a regulatory function of mucosal xanthine oxidase in purine salvage by the small intestine.
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PMID:The effect of nutritional state and allopurinol on nucleotide formation in enterocytes from the guinea pig small intestine. 200 79

Inherited adenine phosphoribosyltransferase (APRT) has a recessive transmission. When it is very important, adenine can't be restored into nucleic acids pool and will changed into 2,8-dihydroxyadenine (2,8-DHA) by xanthine oxidase. To date in all countries but Japan, 2,8-DHA urolithiasis is observed only into homozygotic subjects with complete APRT deficiency Commonly, its onset is observed in childhood often dramatically. The authors report two new pediatric cases into new french families. First a 8 years old boy with spontaneous elimination of two lithiasis after right lumbar pain. Secondly an infant (nineteen months) who has presented an acute renal failure with anuria. Bilateral lithiasis included into pyelourectal junctions have been pulled out by bilateral surgical pyelotomy. In each case, lithiasis were radiolucent and diagnosis made by ultrasonography. The uric acid metabolism was normal and it is the infra red spectrophotometric study of stones that had recognised the 2,8-DHA component. In the second case, bilateral residual lithiasis have been broken by piezoelectric extra-corporeal lithotripsy with good tolerance and favorable result. The two children received preventive treatment. After 36 and 19 months they have no recurrence. In the literature, the frequency of 2,8-DHA lithiasis is very more low than the theoretical of homozygotics in population (1/100,000). The common confusion with uric lithiasis is one possible explanation. So spectrophotometric study of radiolucent stones was meant to be realised when uric metabolism is not disturbed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[2,8-dihydroxyadenine lithiasis. 2 new pediatric cases of an unknown metabolic deficit. The use of extracorporal lithotripsy]. 238

We report the first patient in Finland and Scandinavia with a deficiency of adenine phosphoribosyltransferase (APRT). About 30 clinically affected patients have been reported in the literature. APRT deficiency is an enzyme disorder which is inherited autosomally in a recessive manner. The use of adenine in purine metabolism is disturbed and it accumulates in the body, where it is oxidised to poorly insoluble 2,8-dihydroxyadenine by xanthine oxidase. The dihydroxyadenine forms stones which can be mistaken for uric acid stones. Our patient had had frequent episodes of urolithiasis and the diagnosis was finally made after pyelolithotomy and stone analysis. The total APRT deficiency was detected in the haemolysate of erythrocytes. Partial deficiency of APRT in the patient's relatives showed heterozygosity of the enzyme defect. The only clinical manifestation of the defect is the formation of urinary stones. This can be prevented by diet and allopurinol.
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PMID:Adenine phosphoribosyltransferase deficiency: 2,8-dihydroxyadenine urolithiasis in a 48-year-old woman. 280 78

APRT deficiency is an enzyme disorder which is inherited as an autosomal recessive trait. The use of adenine in purine metabolism is disturbed and it accumulates in the body, where it is oxidised by xanthine oxidase to poorly insoluble 2, 8-dihydroxyadenine (DHA). The dihydroxyadenine forms stones which cause recurrent urolithiasis, frequent episodes of urinary tract infection or interstitial nephritis, and finally renal insufficiency in some cases. We report a case of APRT deficiency discovered by urine examination. The patient was a 33-year-old man who had never had any episodes of urolithiasis. He was admitted to our hospital because of pseudoarthrosis of his left arm caused by a traffic accident. His urinalysis revealed no proteinuria nor hematuria, but disclosed numerous round brown crystals in the sediment. These crystals had the characteristics of 2, 8-DHA. The enzyme activity of APRT in his blood was completely deficient. He was diagnosed as an APRT* QO homozygote. In addition, diagnostic imaging revealed that his right kidney was poorly hypoplastic and the pelvis of his left kidney was extra-renal. The renal function was slightly disturbed. In Japan 6 cases of 2, 8-DHA urolithiasis associated with hypoplastic kidney had been reported by 1989. Theoretically, the incidence of hypoplastic kidney is around 20% of all 2, 8-DHA urolithiasis cases. We suspect a genetic correlation between hypoplastic kidney and APRT deficiency. This patient was treated with Allopurinol, which inhibits the process of xanthine oxidation, after which crystals were no longer detected in his urine.
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PMID:[A case of adenine phosphoribosyltransferase (APRT) deficiency discovered by urine examination]. 781 52

Deficiencies in different steps of purine metabolism give rise to a number of human inherited disorders. Lesch-Nyhan syndrome is a severe neurological disorder, caused by a deficiency in the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT). HPRT-deficient mice have been generated, but have proved to be an unsuccessful model of the human disease. We have suggested that this may be due to a greater dependency in rodents on the other purine salvage enzyme, adenine phosphoribosyltransferase (APRT). We have generated an APRT-deficient mouse line by gene targeting, with a phenotype that closely resembled the symptoms of APRT deficiency in man. APRT null mice were viable, but 90% died prematurely before 6 months of age, displaying highly abnormal kidney morphology, with pathology characteristic of tubule obstruction. These mice have elevated urinary levels of adenine and 2,8-dihydroxyadenine, a highly insoluble adenine derivative, plus birefringent crystalline deposits and calculi within tubules throughout the kidney. A standard therapy for APRT-deficient human patients is the administration of the xanthine oxidase inhibitor, allopurinol. This has proved an effective therapy for APRT null mice, preventing accumulation of 2,8-dihydroxyadenine and much of the resultant renal obstruction, allowing us to establish a breeding line. We believe that these mice should provide a useful model for further study of APRT deficiency in humans. Furthermore, by generating APRT and HPRT double mutants, we will be able to test our hypothesis that both genes must be inactivated in mice before a model for Lesch-Nyhan syndrome can be obtained.
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PMID:Mice with adenine phosphoribosyltransferase deficiency develop fatal 2,8-dihydroxyadenine lithiasis. 886 50

The molecular and biochemical aspects of purine nucleotide biosynthesis through de novo and salvage pathways, the production of uric acid, and their regulation mechanisms are reviewed for further understanding of hyperuricemia and gout. The metabolic rate of purine nucleotide biosynthesis is chiefly determined by the regulation of the de novo pathway, especially amidophosphoribosyltransferase and PRPP synthetase, and the accumulation of uric acid results from the acceleration of de novo biosynthesis and catabolism of purine nucleotide or the decrease in urinary excretion of uric acid. Moreover, several enzyme mutations of purine nucleotide metabolism are also clinically important including gout with hyperactive HPRT and the deficiency of HPRT (Lesch-Nyhan syndrome), adenylosuccinate lyase, xanthine oxidase, APRT, PNP, or ADA (SCID) with gene therapy.
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PMID:[Metabolism of purine nucleotides and the production of uric acid]. 897 90

The activities of purine salvage enzymes in tachyzoites from a cyst-forming strain of Toxoplasma gondii were determined using HPLC. Six enzymes were assayed both in vitro and in vivo: adenosine deaminase, guanine deaminase, purine nucleoside phosphorylase, xanthine oxidase, hypoxanthine-guanine phosphoribosyltransferase and adenine phosphoribosyltransferase. In vitro, the tachyzoites were cultured in the human myelomonocytic cell line THP-1, for 24 h to 96 h. Neither guanine deaminase nor hypoxanthine-guanine phosphoribosyltransferase activity was detected in 24 and 96 h cultures. In vivo, in controls and infected animals, the purine nucleoside phosphorylase and adenosine deaminase activities were the most important activities both in sera and cerebral tissue in comparison with the other activities. It was also noted that the infection modified the enzymatic activities of this purine salvage pathway, in particular, the guanine deaminase cerebral activity of infected mice was 20-fold lower than the value of controls. The treatment of mice with 2',3'-dideoxyinosine, a purine analog, at the dose of 100 mg.kg(-1).d for 30 days, induced an important increase of all enzymatic activities in the brains in comparison with control animals. These data suggest that one target of 2',3'-dideoxyinosine is the purine metabolism.
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PMID:Purine pathway enzymes in a cyst forming strain of Toxoplasma gondii. 1057 52

To examine the effect of 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid (TEI-6720), an inhibitor of xanthine oxidase, on purine metabolism in the lung cancer cell line A549, the activities of adenosine deaminase, purine nucleoside phosphorylase, adenine phosphoribosyltransferase, hypoxanthine guanine phosphoribosyltransferase, xanthine oxidase, and guanase together with pyrimidine nucleoside phosphorylase were measured with or without the addition of TEI-6720, and the extracellular concentrations of hypoxanthine, xanthine, inosine, uracil, and uridine were measured after the addition of inosine or uridine to the incubation medium with or without TEI-6720. Moreover, the Na-independent nucleoside transport was determined in A549 cells with or without TEI-6720. TEI-6720 inhibited the activity of xanthine oxidase in A549 cells, but did not affect other enzymes. During incubation, TEI-6720 not only prevented a decrease in the inosine concentration in inosine-containing medium, but also a decrease in the uridine concentration in uridine-containing medium. Furthermore, the Na-independent transport of uridine was inhibited by TEI-6720 with a K(i) value of 4.1 micromol/l. These results indicate that TEI-6720 is an inhibitor of the Na-independent nucleoside transport of uridine and inosine, as well as xanthine oxidase.
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PMID:Effect of TEI-6720, a xanthine oxidase inhibitor, on the nucleoside transport in the lung cancer cell line A549. 1062 41

A case is presented of a 41-year-old man with a history of recurrent renal stones over 10 years. Analysis of the stone showed that, although it gave a positive reaction with the non-specific phosphotungstic acid test, uricase failed to identify any urate present. Analysis in a reference laboratory confirmed its composition as dihydroxyadenine. Patients who are homozygous for the rare autosomal-recessive adenine phosphoribosyltransferase deficiency, excrete large amounts of 2,8-dihydroxyadenine, which has poor solubility at normal urinary pH. Treatment with the xanthine oxidase inhibitor allopurinol induces a total cessation of stone formation. Increased awareness of the condition and knowledge of the limitations of some methods of laboratory analysis for renal stones should help to identify this type of stone and prevent renal damage.
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PMID:2,8-Dihydroxyadenine renal stones in a 41-year-old man. 1502 10


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