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)

Purine metabolism and reutilization pathways were studied as they applied to normal and leukemic leukocytes. The enzyme activities were expressed in terms of the quantity of protein extracted and per 10(10) cells. Whereas the protein extracted and the enzyme activities from normal lymphocytes were relatively constant, considerable variation was noted in cases of chronic lymphocytic leukemia (CLL). This variability in the properties of the leukemic cells suggests that the difference may be useful in the subclassification of the leukemias. The studies of the complete enzyme system were done with 300 million cells. The extraction of 350,000 normal lymphocytes/mul gave a soluble protein concentration of 1.46+/-0.16 mg protein per ml, and the yield from the same number of CLL lymphocytes varied between 0.72 and 8.32 mg protein per ml. The 5'-nucleotidase activity gave an inverse correlation with the amount of extractable protein. In individual cases of CLL, the protein concentrations and the 5'-nucleotidase activities were found on either side of the normal values. In most cases, the adenosine deaminase of CLL lymphocytic cell extracts was lower than normal, and the adenosine kinase was higher; in the CLL cells, these two enzymes gave a positive correlation with one another. Little or no difference was observed in the activities of the purine nucleoside phosphorylases in extracts of normal or leukemic lymphocytes and granulocytes. The hypoxanthine-guanine and adenine phosphoribosyltransferase activities increased in the leukemic granulocytes but almost always showed a decrease in the CLL lymphocytes when compared with the normal cells. Most of the leukemic cells had greater than normal activities of the enzymes synthesizing phosphoribosyl pyrophosphate when tested with the purines. The total nucleotide produced from adenine and guanine with adenine- and hypoxanthine-guanine phosphoribosyltransferase was about equal in normal and leukemic lymphocytes, but the proportion of the adenosine 5'-triphosphate in the product was much greater with the leukemic cells. This suggested that the ribosyltransferase activities were the same in both types of cells, but the nucleoside kinases and the nucleoside diphosphate kinases were more active in the leukemic cells. Inosine monophosphate dehydrogenase was less active than normal in the CLL cell extracts and was not directly related to the amount of inosine monophosphate generated from hypoxanthine.
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PMID:Purine metabolic cycle in normal and leukemic leukocytes. 18 45

A model is proposed for the partial depletion of the adenine nucleotide pool in the ischemic perfused rat heart which involves seven enzymes: adenylate cyclase, 3',5'-cyclic AMP phosphodiesterase, 5'-nucleotidase, adenosine kinase, adenosine deaminase, purine nucleoside phosphorylase, and inorganic pyrophosphatase. The computer implementation of this model is in terms of rate laws, several of which were obtained by a systematic least-squares fitting procedure. Depletion of the adenine nucleotide pool is initiated by the release of endogenous noradrenaline into the interstitial fluid, which results from a fall in tissue PO2, and the subsequent activation of adenylate cyclase. In this model the substrate for 5'-nucleotidase is a membrane-bound AMP pool formed by hydrolysis of extracellular fluid and functions as a vasodilator; excess adenosine is incorporated into the tissue by a "permease" with Michaelis-Menten kinetics and converted to AMP, inosine, and hypoxanthine. Alternative mechanisms, such as the deamination of AMP by adenylate deaminase and conversion of AMP to adenine by AMP pyrophosphorylase, were rejected primarily on qualitative biochemical grounds.
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PMID:Computer simulation of ischemic rat heart purine metabolism. I. Model construction. 19 89

Changes in hepatic purine enzyme activities of chicks fed diets containing 11%, 20%, 43% and 80% protein were correlated with protein intake and uric acid production in order to identify those enzymes with activities that parallel closely and may regulate uric acid production. Nucleoside phosphorylase, xanthine dehydrogenase, adenylosuccinate synthetase and adenosine kinase correlated positively with protein intake and uric acid production. Adenosine deaminase, 5'-nucleotidase (AMP), adenylate deaminase and adenine phosphoribosyltransferase correlated negatively with protein intake and uric acid production. Hypoxanthine phosphoribosyltransferase and 5'-nucleotidase (IMP) were unaffected by protein intake and did not correlate with uric acid production. The ratio of adenosine kinase to adenosine deaminase correlated positively with protein intake and uric acid production. The increased activities of adenylosuccinate synthetase and adenosine kinase, along with the reduced activities of 5'-nucleotidase and adenylate deaminase, in liver from chickens fed the 80% compared with the 11% protein diet demonstrate enhanced synthesis of adenine nucleotides. Since adenine nucleotides are essential cofactors for de novo purine synthesis, it is proposed that adenylosuccinate synthetase, adenosine kinase, 5'-nucleotidase and adenylate deaminase are key enzymes involved in the regulation of purine biosynthesis.
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PMID:Protein intake, hepatic purine enzyme levels and uric acid production in growing chicks. 61 42

The finite life-span of fibroblasts in culture may reflect aging at the cellular level and gout is clinical condition whose incidence also increases with age. In order to better understand the age-related changes in purine metabolism, activities of purine degrading (adenosine deaminase and 5'-nucleotidase) and reutilizing (adenine phosphoribosyltransferase, hypoxanthine phosphoribosyl-transferase and adenosine kinase) enzymes were measured in serially cultured skin fibroblasts from normal subjects and from gouty patients who overproduce uric acid. Serially cultured fibroblasts from gouty overproducers of uric acid displayed increased purine enzyme levels with increasing cell passage while fibroblasts from normal donors showed little change in activity. There was no alteration in relative degrading and reutilizing enzyme levels. The data suggest an increase in the rate of purine turnover in aging gouty fibroblasts compared with normal fibroblasts.
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PMID:Activities of purine pathway enzymes in gouty human fibroblasts aged in vitro. 83 27

1. The hypoxanthine/guanine and adenine phosphoribosyltransferase activities in a wide variety of human tissues were studied during their growth and development from foetal life onward. A wide range of activities develop after birth, with especially high values in the central nervous system and testes. 2. Postnatal development of hypoxanthine/guanine phosphoribosyltransferase was also defined in the rat. Although there were increases in the central nervous system and testes, there was also a rise in activity in the liver, which was less marked in man. 3. A sensitive radiochemical assay method, using dTTP to inhibit 5'-nucleotidase activity, suitable for tissue extracts, was developed. 4. No definite evidence of the existence of tissue-specific isoenzymes of hypoxanthine/guanine or adenine phosphoribosyltransferase was found. Hypoxanthine/guanine phosphoribosyltransferase in testes, however, had a significantly different thermal-denaturation rate constant. 5. The findings are discussed in an attempt to relate activity of hypoxanthine/guanine phosphoribosyltransferase to biological function. Growth as well as some developmental changes appear to be related to increase in the activity of this enzyme.
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PMID:Developmental changes in purine phosphoribosyltransferases in human and rat tissues. 101 39

To evaluate the regulation of adenine nucleotide metabolism in relation to purine enzyme activities in rat liver, human erythrocytes and cultured human skin fibroblasts, rapid and sensitive assays for the purine enzymes, adenosine deaminase (EC 2.5.4.4), adenosine kinase (EC 2.7.1.20), hyposanthine phosphoribosyltransferase (EC 2.4.28), adenine phosphoribosyltransferase (EC 2.4.2.7) and 5'-nucleotidase (EC 3.1.3.5) were standardized for these tissues. Adenosine deaminase was assayed by measuring the formation of product, inosine (plus traces of hypoxanthine), isolated chromatographically with 95% recovery of inosine. The other enzymes were assayed by isolating the labelled product or substrate nucleotides as lanthanum salts. Fibroblast enzymes were assayed using thin-layer chromatographic procedures because the high levels of 5'-nucleotidase present in this tissue interferred with the formation of LaCl3 salts. The lanthanum and the thin-layer chromatographic methods agreed within 10%. Liver cell sap had the highest activities of all purine enzymes except for 5'-nucleotidase and adenosine deaminase which were highest in fibroblasts. Erythrocytes had lowest activities of all except for hypoxanthine phosphoribosyltransferase which was intermediate between the liver and fibroblasts. Erhthrocytes were devoid of 5'-nucleotidase activity. Hepatic adenosine kinase activity was thought to control the rate of loss of adenine nucleotides in the tissue. Erythrocytes had excellent purine salvage capacity, but due to the relatively low activity of adenosine deaminase, deamination might be rate limiting in the formation of guanine nucleotides. Fibroblasts, with high levels of 5'-nucleotidase, have the potential to catabolize adenine nucleotides beyond the control od adenosine kinase. The purine salvage capacity in the three tissues was erythrocyte greater than liver greater than fibroblasts. Based on purine enzyme activities, erythrocytes offer a unique system to study adenine salvage; fibroblasts to study adenine degradation; and liver to study both salvage and degradation.
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PMID:Adenine nucleotide metabolism in relation to purine enzymes in liver, erythrocytes and cultured fibroblasts. 118 98

The activities (Vmax) of several enzymes of purine nucleotide metabolism were assayed in premature and mature primary rat neuronal cultures and in whole rat brains. In the neuronal cultures, representing 90% pure neurons, maturation (up to 14 days in culture) resulted in an increase in the activities of guanine deaminase (guanase), purine-nucleoside phosphorylase (PNP), IMP 5'-nucleotidase, adenine phosphoribosyltransferase (APRT), and AMP deaminase, but in no change in the activities of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenosine deaminase, adenosine kinase, and AMP 5'-nucleotidase. In whole brains in vivo, maturation (from 18 days of gestation to 14 days post partum) was associated with an increase in the activities of guanase, PNP, IMP 5'-nucleotidase, AMP deaminase, and HGPRT, a decrease in the activities of adenosine deaminase and IMP dehydrogenase, and no change in the activities of APRT, AMP 5'-nucleotidase, and adenosine kinase. The profound changes in purine metabolism, which occur with maturation of the neuronal cells in primary cultures in vitro and in whole brains in vivo, create an advantage for AMP degradation by deamination, rather than by dephosphorylation, and for guanine degradation to xanthine over its reutilization for synthesis of GMP. The physiological meaning of the maturational increase in these two ammonia-producing enzymes in the brain is not yet clear. The striking similarity in the alterations of enzyme activities in the two systems indicates that the primary culture system may serve as an appropriate model for the study of purine metabolism in brain.
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PMID:Developmental changes in the activity of enzymes of purine metabolism in rat neuronal cells in culture and in whole brain. 232 47

A reliable assay was developed to characterize crude cell homogenates with regard to their adenine phosphoribosyltransferase activities. The 5-phosphoribosyl-1-pyrophosphate (PRPP)-dependent formation of AMP from adenine is followed spectrophotometrically at 265 nm by coupling it with the following two-stage enzymatic conversion: AMP + H2O----adenosine + Pi (5'-nucleotidase); adenosine + H2O----inosine + NH3 (adenosine deaminase). The same principle was applied to develop a spectrophotometric and a radioenzymatic assay for PRPP. The basis of the spectrophotometric assay is the absorbance change at 265 nm associated with the enzymatic conversion of PRPP into inosine, catalyzed by the sequential action of partially purified adenine phosphoribosyltransferase, commercial 5'-nucleotidase, and commercial adenosine deaminase, in the presence of excess adenine. In the radiochemical assay PRPP is quantitatively converted into [14C]inosine via the same combined reaction. Tissue extracts are incubated with excess [14C]adenine. The radioactivity of inosine, separated by a thin-layer chromatographic system, is a measure of PRPP present in tissue extracts. The radioenzymatic assay is at least as sensitive as other methods based on the use of adenine phosphoribosyltransferase. However, it overcomes the reversibility of the reaction and the need to use transferase preparations free of any phosphatase and adenosine deaminase activities.
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PMID:A coupled optical assay for adenine phosphoribosyltransferase and its extension for the spectrophotometric and radioenzymatic determination of 5-phosphoribosyl-1-pyrophosphate in mixtures and in tissue extracts. 244 24

The enzymes that catalyse the salvage of purines in Entamoeba histolytica trophozoites have been surveyed. Adenine deaminase (EC 3.5.4.2), adenosine deaminase (EC 3.5.4.4), guanine deaminase (EC 3.5.4.3), adenine phosphoribosyltransferase (PRTase) (EC 2.4.2.7), xanthine PRTase (EC 2.4.2.22) and hypoxanthine PRTase (EC 2.4.2.8) were all detected in cell homogenates but only at low activities, whereas AMP deaminase (EC 3.5.4.6) and guanine PRTase (EC 2.4.2.8) were not found. Phosphorylases (EC 2.4.2.1) active in both anabolic and catabolic directions were present and all nucleosides tested were phosphorylated by kinases (EC 2.7.1.15, EC 2.7.1.20, EC 2.7.1.73). 3'-Nucleotidase (EC 3.1.3.6) and 5'-nucleotidase (EC 3.1.3.5) were found, the former being mainly particulate. Nucleotide interconversion enzymes (adenylosuccinate lyase, EC 4.3.2.2; adenylosuccinate synthetase, EC 6.3.4.4; IMP dehydrogenase, EC 1.2.1.14; GMP synthetase, EC 6.3.5.2 and GMP reductase, EC 1.6.6.8) were not detected. The results suggest that in E. histolytica the main route of nucleotide synthesis is from the individual bases through the actions of phosphorylases and kinases.
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PMID:Purine-metabolising enzymes in Entamoeba histolytica. 287 91

Adenosine 5'-triphosphate (ATP) was catabolized by whole cells and cell-free extracts of Rickettsia typhi to adenosine 5'-diphosphate (ADP) and then to adenosine 5'-monophosphate (AMP), the end product of ATP catabolism under the experimental conditions used. The only intermediate of the pathway from ATP to AMP which was identified by thin-layer chromatography and quantitated by the (14)C content was ADP, whereas products such as adenine, adenosine, hypoxanthine, inosine, and inosine 5'-monophosphate were not detected. The enzymes which could be theoretically responsible for the catabolism or the anabolism of AMP were not detected by standard assay procedures. Most importantly, 5'-nucleotidase or nonspecific phosphatase and AMP nucleosidase activities were undetectable under a variety of experimental conditions. Although these two enzymes remove AMP from the adenylate pool in other cells, they are apparently nonfunctional in R. typhi. The biosynthesis of ATP was initiated by adenylate kinase because no adenine phosphoribosyltransferase or adenosine kinase could be detected. Furthermore, AMP was transported intact without prior dephosphorylation. These observations suggest that for R. typhi the in vivo activity of adenine nucleotide interconversion was limited to the nucleotides, with AMP being the end product of ATP catabolism, and that the salvage of purine bases and nucleosides was not an essential feature of purine metabolism. These results elucidate the findings of a previous study which showed that in the absence of glutamate as a source of energy, the adenylate energy charge of resting cells of R. typhi is drastically lowered by the high proportion of AMP.
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PMID:Adenine nucleotide degradation by the obligate intracellular bacterium Rickettsia typhi. 624 88


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