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)

Our experience with the prenatal detection of the Lesch-Nyhan syndrome (LNS; hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency) in three fetuses at risk is reported. Enzyme activities were measured in cultured amniocytes in two pregnancies, and in tissues and cultures obtained from chorionic villus sampling (CVS) in a third pregnancy. In all tissues the specific activities of HGPRT and adenine phosphoribosyltransferase (APRT) were determined and APRT/HGPRT ratios were calculated. In addition to the enzyme assays, the rate of purine synthesis de novo was assessed in the two amniocyte cultures, and the rate of [14C]hypoxanthine incorporation into nucleotides and sensitivity to azaguanine were measured in one of the amniocyte cultures. We report the diagnosis of normal fetuses by study of amniocytes in two pregnancies and of LNS using CVS in one pregnancy. In all three cases the diagnosis was confirmed.
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PMID:Prenatal diagnosis of Lesch-Nyhan syndrome: experience with three fetuses at risk. 279 51

Simple methods for the detection of hypoxanthine-guanine phosphoribosyltransferase and/or adenine phosphoribosyltransferase deficiencies using dried filter paper blood spots were studied. Enzyme activities in the eluate from dried filter paper blood spots stored for 4 weeks at room conditions were shown to be quite stable. Autoradiographs prepared from dried filter paper blood spots and DE-81 papers soaked with enzyme reaction mixtures containing 14C-hypoxanthine and/or 14C-adenine showed sharp radioactive spots in normal subjects. No activity was evident in the cases of the Lesch-Nyhan syndrome and/or adenine phosphoribosyltransferase deficiency. The methods seem to be suitable for screening.
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PMID:Simple screening methods for hypoxanthine-guanine phosphoribosyltransferase and adenine phosphoribosyltransferase deficiencies using dried blood spots on filter paper. 376 88

IMP:pyrophosphate phosphoribosyltransferase (IPPase) (EC 2.4.2.8) has been purified over 7000-fold from human erythrocytes. The purified enzyme moved as a single band on disc electrophoresis. Antisera prepared in rabbits and rats against the purified enzyme precipitated and neutralized the enzyme, but had no effect on AMP-pyrophosphate phosphoribosyltransferase (EC 2.4.2.7) activity. Evidence was found for isozymes (enzyme variants) of IPPase in normal erythrocytes. Erythrocyte lysates of five patients with Lesch-Nyhan disease reacted with antisera against normal IPPase. Lysates from LN erythrocytes blocked the inactivation of normal enzyme by the antibody. LN erythrocytes had about the same concentration of enzyme protein as normal erythrocytes. The genetic defect in LN results in the production of essentially normal amounts of an immunologically identifiable but catalytically incompetent enzyme. Thus LN is apparently the result of a mutation in a structural gene and is not due to deletion of a structural gene or defect in a regulatory gene.
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PMID:Purification of IMP:pyrophosphate phosphoribosyltransferases, catalytically incompetent enzymes in Lesch-Nyhan disease. 432 3

(1) This communication reports the amidophosphoribosyltransferase (PRPP-At; EC2.4.2.14), hypoxanthine phosphoribosyltransferase (HPRT; EC2.4.2.7) and adenine phosphoribosyltransferase (APRT; EC2.4.2.8) activities and the phosphoribosylpyrophosphate (PRPP) content of rat brain at different stages of development. The results are not age-related in the foetal and neonatal animals and the data for whole brain homogenates are similar to the average results for the individual regions of the brain at the same stage of development. (2) The enzyme activities and PRPP content are similar in the different regions of the rat central nervous system. PRPP-At has the lowest activity of the 3 enzymes studied and this decreases gradually from birth until 8 weeks. HPRT is the most active of the three enzymes, its activity increases markedly between birth and the end of the third week of life. The time course of these changes shows only minor differences between the regions of the brain studied. The ratio of HPRT activity to PRPP-At activity increases from age 1 week in all parts of the rat brain. (3) The APRT activities in rat brain are intermediate between those of PRPP-At and HPRT and essentially steady except for a decrease in the cerebellum during the first 3 weeks of life. (4) The PRPP concentrations in rat brain decrease between birth and the end of the 3rd week of life. (5) The systemic tissues examined have PRPP-At, HPRT and APRT activities. The relationship between the activities of the different enzymes appears to be characteristic of the tissue concerned. (6) Correlating the observed time course of the changes in the ratio of hypoxanthine phosphoribosyltransferase activity to amidophosphoribosyltransferase activity in the rat with other workers' data on changes in the rate of DNA accretion in human brain during development indicates that the main increase in this ratio is after the major bursts of neuroblast and neuroglia proliferation. We suggest that the neurological dysfunction in the Lesch-Nyhan syndrome is due to lack of a purine derivative with a physiological or neuropharmacological function, rather than to an effect of the biochemical lesion on brain morphogenesis.
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PMID:Activities of amidophosphoribosyltransferase (EC2.4.2.14) and the purine phosphoribosyltransferases (EC2.4.2.7 and 2.4.2.8), and the phosphoribosylpyrophosphate content of rat central nervous system at different stages of development--their possible relationship to the neurological dysfunction in the Lesch-Nyhan syndrome. 615 47

An overview of inherited disorders of purine metabolism, concentrating on well established enzyme defects is given. Included are HPRT and the LNS, APRT and 2,8-dihydroxyadenine lithiasis, hyperactivity of PRPP synthetase, ADA and PNP and immunodeficiencies. Emphasis is put on underlying molecular mechanisms on the gene-, enzyme-, or metabolite level for a better understanding of the events leading from the genotype to the clinical phenotype. Finally some aspects of extracellular purine nucleotide metabolism catalyzed by cell surface-bound ectoenzymes are discussed.
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PMID:Inherited disorders of purine metabolism--underlying molecular mechanisms. 620 48

We have measured the rate of purine synthesis de novo in blood mononuclear cells in vitro and the activities of the purine salvage enzymes [hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8), adenine phosphoribosyltransferase (APRT; EC 2.4.2.7)] and ribosephosphate pyrophosphokinase (PP-ribose-P synthetase; EC 2.7.6.1)] and the concentration of phosphoribosylpyrophosphate (PP-ribose-P) in the erythrocytes of affected family members. These subjects belong to families where hyperuricaemia and renal failure occur together early in life, and the genetic transmission follows an autosomal dominant mode of inheritance. We term this syndrome, familial hyperuricaemic nephropathy. No significant differences were detected in either the rates of purine synthesis de novo in vitro between the index patients and the control subjects with respect to the enzyme activities or the PP-ribose-P concentrations. Two groups of controls were used, healthy individuals and patients with a comparable degree of renal failure due to non-immune complex renal disease. Mononuclear cells from patients with Lesch-Nyhan syndrome (congenital HPRT deficiency) showed the expected acceleration of purine synthesis de novo in vitro. The accelerated purine synthesis de novo in vitro associated with phytohaemagglutinin-induced lymphocyte transformation was detectable by the method used. We conclude that familial hyperuricaemic nephropathy is not due to a metabolic lesion which causes accelerated purine synthesis de novo. This suggests that the primary abnormality may be a failure of the renal tubular net excretion of urate.
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PMID:The rate of purine synthesis de nova in blood mononuclear cells in vitro from patients with familial hyperuricaemic nephropathy. 674 92

Authors present a 10 year old boy with Lesch-Nyhan syndrome with self-inflicted mutilations to the lips, tongue and interior cheek wall, partially avoided by tooth extraction. Hand lesions were prevented by arm restriction. Born with anoxia and in spite of seizures for several years and a marked muscle stiffness, he is relatively aware of his surroundings. HGPRT activity in blood and hair was nil, while the APRT activity was increased. The mother, a maternal aunt and grandmother are not carriers. Hyperuricemia measured several times and treated with allopurinol is kept between 3 and 4 mg/dl and lastly under 3 mg after increasing dosage. Some years ago, elimination of acid uric stones in urine was observed without hematuria. It seems that recently stone elimination produced pain difficult to evaluate in this patient.
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PMID:[Report of a patient with Lesch-Nyhan syndrome caused by total deficiency of HGPRT and with normal activity in female family members]. 713 25

Purine metabolism was studied and an enzymatic deficiency was detected in 6 girls with Lesh - Nyhan syndrome/LNS/. In erythrocytes of the patients with LNS and of their parents alterations were found in activities of hypoxanthine guanine phosphoribosyl transferase/HGPRT/ and adenine phosphoribosyl transferase/APRT/. A form of LNS was observed, which exhibited a decrease in stability of HGRPT and alteration in sensitivity of the enzyme to inhibitors. Treatment with allopurinol did not affect the HGRPT and APRT activities. Heterogeneity of the Lesh Nyhan syndrome is discussed.
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PMID:[Erythrocyte purine phosphoribosyltransferase activity in girls with the Lesch-Nyhan syndrome]. 729 80

A large Arab family affected with the rare X-linked Lesch-Nyhan syndrome is reported on. Two hemizygous boys, two and nine years of age, had the classical biochemical and clinical-neurological syndrome. The activity of erythrocyte hypoxanthine-guanine phosphoribosyltransferase (HGPRT) was below the detectable limit (greater than 0.1% of normal). They were mentally and physically retarded and exhibited spasticity and choreoathetosis; the older of the two also exhibited self-mutilation. The mother and three of her seven daughters, all clinically asymptomatic, were proven to be heterozygous for HGPRT deficiency, by demonstration of an increased rate of de novo purine synthesis in cultured skin fibroblasts. Erythrocyte HGPRT activity was normal in the three heterozygous daughters, but was significantly reduced in the mother. However, in all four heterozygotes, erythrocyte HGPRT/adenine phosphoribosyltransferase ratio was lower than in all other family members. All heterozygotes had blood uric acid levels within the normal range, although higher than in the normal women in the family. The ratio uric acid/creatinine concentration in the urine was significantly elevated in one of the heterozygotes, and in the upper normal limit in two others, indicating excessive purine production.
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PMID:Lesch-Nyhan syndrome in an Arab family. Detection and biochemical manifestation of heterozygosity. 732 17

Activities of phosphoribosyltransferase for hypoxanthine and adenine were investigated in erythrocytes and human tissues of fetuses and adults as well as in cultivated fibroblasts and amniotic fluid cells. Kinetic characteristics of these enzymes were also studied in patients with the Lesch-Nyhan syndrome and with partial deficiency for hypoxanthine phosphoribosyltransferase (HGPRTase), and their obligate heterozygotes. The affinity of HGPRTase for both substrates in partial deficiency decreased to 13 to 20% of normal and by a less degree in its heterozygotes (50 to 65% of normal). A slight decrease in the Km for phosphoribosylpyrophosphate was observed in the case of heterozygotes for the Lesch-Nyhan syndrome. Elevated erythrocytic adenine phosphoribosyltransferase (APRTase) activity was found in fetuses, patients with the Lesch-Nyhan syndrome or with partial deficiency, and in some heterozygotes as well. However, the Km of APRTase for hypoxanthine in these subjects was the same as that in the normal adults. The HGPRTase activity in liver increased almost 4 times during the developmental period, whereas the APRTase activity remained approximately the same. In fetal liver, the APRTase activity was almost two times higher than the HGPRTase activity, whereas in fetal brain the HGPRTase activity was higher. The Km of HGPRTase for hypoxanthine in cultivated cells and human tissues were similar to that in erythrocytes and leukocytes. On the other hand, the HGPRTase affinity for phosphoribosylpyrophosphate in these cells was cconsiderably larger than in erythrocytes or in leukocytes.
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PMID:Prenatal diagnosis of Lesch-Nyhan syndrome and some characteristics of hypoxanthine-guanine phosphoribosyltransferase and adenine phosphoribosyltransferase in human tissues and cultivated cells. 740 56


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