Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In subconfluent cultures of fibroblasts from patients with complete or partial deficiencies of hypoxanthine-guanine phosphoribosyltransferase, phosphoribosylpyrophosphate synthetase activity is elevated. The abnormally high catalytic activity of the synthetase appears to account for the overproduction of purines by the cultured mutant cells and presumably for that by the patients.
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PMID:Phosphoribosylpyrophosphate synthetase is elevated in fibroblasts from patients with the Lesch-Nyhan syndrome. 18 Jun 3

The uptake of hypoxanthine by Chinese hamster lung fibroblasts grown in tissue culture was studied in wild type clones and 8-azaguanine-resistant mutant clones devoid of hypoxanthine-guanine phosphoribosyltransferase. Wild type fibroblasts rapidly accumulate [3H]hypoxanthine from the medium and over 80% of the intracellular radioactivity is found in acid-soluble nucleotides. The phosphoribosyltransferase-deficient clones accumulate much lower levels of hypoxanthine and over 85% of the intracellular 3H label is associated with chemically unaltered hypoxanthine. The internal level of hypoxanthine in the mutant clones rapidly approaches but does not exceed that present in the medium. Wild type and phosphoribosyltransferase-deficient cells take up hypoxanthine at almost identical initial rates at external hypoxanthine levels from 2 to 300 muM. Analysis of these data reveals two transport systems that obey the Michaelis-Menten relationship. These differ markedly in affinity, yielding average Km values of 20 and 600 muM for both cell types. Hypoxanthine transport by both low and high affinity transport systems is blocked by p-chloromercuriphenylsulfonate and N-ethylmaleimide. Counter-transport of hypoxanthine was demonstrated in phosphoribosyltransferase-deficient fibroblasts. It is concluded that hypoxanthine is transported into Chinese hamster cells by means of carrier-mediated processes (facilitated diffusion) that operate independently of phosphoribosylation.
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PMID:Hypoxanthine transport by cultured Chinese hamster lung fibroblasts. 18 79

1. Total lipids, total cholesterol, cholesterol esters, phospholipids, triglycerides and free fatty acids as well as the fatty acids profiles of the different lipid classes were determined in serum, lipomatous and normal adipose tissue. Triglycerides were elevated in patient L's serum. The distribution of serum lipoproteins in this patient's serum showed a type IV according to Fredrickson. All other lipid parameters were within the normal range. Palmitoleic acid was increased nearly in all lipid fractions of the patients' sera as well as in the lipids of lipomatous subcutaneous adipose tissue. 2. The lipomatous adipose tissues of the patients showing no histological abnormalities revealed higher levels of cyclic AMP than normal subcutaneous adipose tissue. 3. Serum uric acid was normal (patient E.), between the normal and pathological range (patient L.) and elevated (patient W.). Urinary uric acid excretion was increased in all three patients. 4. 14C-glycine was overincorporated into urinary uric acid in all three patients. 5. Adenine phosphoribosyltransferase activities in the hemolysates were within the normal range. A decrease of hypoxanthine-guanine phosphoribosyltransferase activities could be demonstrated in two patients' (e., w.) erythrocytes. Erythrocyte phosphoribosylpyrophate synthetase activity was slightly increased in patient L.'s and twice the normal value in patient W.'s erythrocytes.
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PMID:[Biochemistry of benign-symmetrical lipomatosis (adenolipomatosis Launois-Bensaude, Madelung's disease)]. 18 73

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

Inactivation of hypoxanthine phosphoribosyltransferase caused by periodate-oxidized GMP is irreversible, even under the conditions of polyacrylamide gel electrophoresis and during affinity chromatography on GMP-Sepharose. Partial binding of the inhibitor to the enzyme protein can be demonstrated on dodecyl sulfate gel electrophoresis: The substrate, phosphoribosyl diphosphate in the presence of Mg2, and the product GMP protect the enzyme against inactivation. Periodate-oxidized GMP, AMP and oxidized purine nucleosides do not influence ribosephosphate pyrophosphokinase, 5'-nucleotidase, purine-nucleoside phosphorylase and guanylate kinase. A variety of other purine nucleosides and nucleotides, tested in their periodateoxidized form, do not lead to a compound comparable or superior to oxidized GMP in its effect on hypoxanthine phosphoribosyltransferase. In an erythrocyte system it is clearly demonstrated that oxidized GMP cannot act across an intact cell membrane.
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PMID:Irreversible inhibition of hypoxanthine phosphoribosyltransferase. Further studies on the specificity of periodate-oxidized GMP. 20 May 44

De novo purine biosynthesis has been studied in lymphocyte cell lines established from Lesch-Nyhan patients deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRT), in in vitro differentiating erythroleukaemic cell lines cloned from cells charactistic of virus-induced murine leukaemia, and in mutant hamster cells deficient in amidophosphoribosyltransferase. The relationship between cellular phosphoribosylpyrophosphate (PP-ribose-P) metabolism and the activity of the enzymes which catalyse the early steps of de novo purine biosynthesis has been explored. It was found that hamster cells deficient in amidophosphoribosyltransferase did not accumulate PP-ribose-P as do HGPRT-deficient cells. In these model systems, an accelerated rate of de novo purine biosynthesis tended to be associated with an increase in cellular PP-ribose-P cotent, but decreases in this rate results from the reduction in the activity of amidophosphoribosyltransferase. Regulation of ammonia-dependent de novo purine biosynthesis was similar to that of glutamine-dependent purine biosynthesis.
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PMID:Purine biosynthesis in mutant mammalian cells. 20 59

Cones of thioguanine resistant K-BALB mouse cells wereisolated which were inducible for endogenous type C virus synthesis by cycloheximide and dexamethsone, but not 5-iododeoxyuridine. A comparison of the number of foci formed on NRK and SC-I cells suggested that the xenotropic virus was suppressed. The variants were not defective in the incorporation of thymidine or iododeoxyuridine or deficient in thymidine kinase, but were deficient in hypoxanthine-guanine phosphoribosyltransferase and the incorporation of hypoxanthine into nucleic acid. Because these cells are blocked at some point in the expression of endogenous virus, they may prove useful in establishing the steps involved in chemical activation of virus synthesis.
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PMID:Isolation of thioguanine resistant variants of K-BALB cells non-inducible for type C viruses by 5-iododeoxyuridine. 20 30

Mouse teratocarcinoma cells from the OTT6050 ascites tumor were established in tissue culture and selected for 5-bromodeoxyuridine (BrdUrd) resistance. The embryonal carcinoma cells grew without a feeder layer, remained deficient for thymidine kinase (EC 2.7.1.75), and differentiated like the original tumor into various tissues after subcutaneous injection into 129 mice. We fused the BrdUrd-resistant mouse teratocarcinoma cells with HT1080-6TG human diploid fibrosarcoma cells deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) and selected for hybrid cells in hypoxanthine/aminopterin/thymidine medium. The resulting hybrid cells segregated human chromosomes quickly and retained one to three human chromosomes including chromosome 17 that carries the human genes for thymidine kinase and galactokinase (EC 2.7.1.6). Single hybrid cells from five independent clones containing human chromosome 17 were injected into mouse blastocysts bearing several genetic markers that affect the coat color phenotype and strain-specific enzyme variants in order to detect tissue differentiation derived from the injected cells. After the injection of single hybrid cells into a total of 103 experimental blastocysts that had been surgically transferred to pseudopregnant foster mothers, 49 mice were born and 2 of them clearly revealed coat mosaicism. In 2 of 17 mice thus far analyzed, the injected hybrid cells proved to be capable of participating substantially in development of seven different organs. However, human gene products have not yet been detected unequivocally in those tissues and weak human-specific galactokinase activity could be recovered only from two mosaic tissues. Our results demonstrate that, after in vitro culture and selection, at least some of the human-mouse hybrid cells still retain their in vivo potential to differentiate and become functionally integrated in the living organism. It now seems feasible to cycle mouse teratocarcinoma cells carrying human genetic material through mice via blastocyst injection to study human gene expression during differentiation.
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PMID:Chimeric mice derived from human-mouse hybrid cells. 20 75

Inhibition of IMP dehydrogenase (EC 1.2.1.14) by ribavirin causes the normal human lymphoblast to excrete increased amounts of newly formed purine into the culture medium. In order for ribavirin to be active as an inhibitor of the dehydrogenase, this synthetic nucleoside must be phosphorylated. The effect of ribavirin on purine excretion has been determined with a normal lymphoblast line, and with lymphoblast lines deficient in hypoxanthine phosphoribosyltransferase (IMP:pyrophosphate phosphoribosyl-transferase, EC 2.4.2.8), in adenosine kinase (ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20), and in both hypoxanthine phosphoribosyltransferase and adenosine kinase. Resistance to the effect of ribavirin on purine excretion was associated only with those cell lines deficient in adenosine kinase activity. These cell lines have normal deoxyadenosine kinase (ATP:deoxyadenosine 5'-phosphotransferase, EC 2.7.1.76) activity. Therefore, the nucleoside kinase activity responsible for ribavirin phosphorylation is adenosine kinase.
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PMID:Adenosine kinase initiates the major route of ribavirin activation in a cultured human cell line. 21 Apr 48

The differences between the uricotelic chick and the ureotelic rat, in the regulation of purine synthesis de novo, were studied in intact liver tissue. Chick liver, in comparison with rat liver, was found to contain a high activity of purine synthesis de novo, a high content and availability of 5-phosphoribosyl 1-pyrophosphate (PP-rib-P), comparable activity of PP-rib-P synthetase, and low activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and of adenine phosphoribosyltransferase (APRT). The results suggest that the intensive activity of the pathway of purine synthesis de novo in the chick liver is mediated by the high PP-rib-P concentration, which may be due at least in part to the relative partial deficiency of HGPRT.
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PMID:Regulation of de novo purine synthesis in chick liver slices. Role of phosphoribosylpyrophosphate availability and of salvage purine nucleotide synthesis. 21 23


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