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)

We have examined the clonal variation in rates of amino acid transport, protein synthesis, protein degradation, growth and proliferation for CHO cells with mutations in the purine and pyrimidine salvage pathways. First we compared three clonal cell lines, each with a different mutation, with the heterozygous parental line AT3-2. Overall, the correlation between rates of protein turnover, growth and proliferation was excellent. The slower growth and proliferation of one mutant, AB3 (TK-, APRT-), is explained by a low intrinsic rate of protein synthesis coupled with a smaller response in rates of amino acid transport, protein synthesis and protein degradation to insulin, serum and dexamethasone. Secondly, we compared seven aza-adenine-resistant and 14 thioguanine-resistant mutants of AT3-2 and found significant differences in control and insulin-stimulated rates of protein turnover both within and between mutant populations. A significant difference between the populations was unexpected because each individual cell line was cloned from a spontaneous pre-existing mutation in AT3-2, and each population should have the same average rate. Remarkably, all 24 mutants had lower rates of protein synthesis than AT3-2. We cannot explain the data solely in terms of mutations in the salvage pathways. Rather, we propose that the mutant survivors have randomly down-regulated the intrinsically fixed growth factor-regulated pathways of protein turnover, resulting in a broad spectrum of lower metabolic rates.
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PMID:Protein turnover, growth and proliferation in CHO cells. Variation within and between mutant classes for salvage pathway enzymes. 154 Jan 46

Tissue-specific animal cell genes are usually fully methylated in the germ line and become demethylated in those cell types in which they are expressed. To investigate this process, we inserted a methylated IgG kappa gene into fibroblasts and lymphocytes at various stages of development. The results show that this gene undergoes demethylation only in the mature lymphocytes and therefore suggest that the ability to demethylate a gene is developmentally regulated. These studies were supported by similar experiments using the rat Insulin I gene, and in this case it appears that the cis-acting elements that control demethylation may be different from those responsible for gene activation. The ability to demethylate the housekeeping gene APRT is also under developmental control, because this occurs only in embryonic cells, both in tissue culture and in transgenic mice.
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PMID:Demethylation of genes in animal cells. 196 61

The proliferative effect of insulin on de novo purine synthesis and on the expression of various enzymes of purine metabolism were studied in primary cultured rat hepatocytes. Insulin greater than 1.5 x 10(-8) M increased DNA and de novo purine synthesis to 260-390 and 270-420%, respectively, 24 and 8 h after the administration. Insulin at 1.5 x 10(-7) M increased the specific activity of amidophosphoribosyltransferase (ATase) to 154-180%, hypoxanthine-guanine phosphoribosyltransferase to 129%, and adenine phosphoribosyltransferase (APRT) to 205%, in contrast to unchanged xanthine dehydrogenase at 80%. Enzyme induction was supported by the results of kinetic analysis and the inhibition of the insulin-induced increase in enzyme activities by protein synthesis inhibitors. Insulin increased ATP to 127% and decreased AMP, ADP, 5'-guanylic acid (GMP), and guanosine 5'-diphosphate (GDP), respectively, to 73, 69, 73, and 69%. Insulin increased adenylate energy charge from 0.83 to 0.90 without changing total feedback inhibitory potential on ATase. No obvious increase of 5-phosphoribosyl-1-pyrophosphate supply was suggested, although its apparent availability for purine ribonucleotide synthesis was increased to 208-245%, reflecting mainly induced APRT activity to 205%. It is concluded that hepatocyte proliferation by insulin, as evidenced by purine metabolism, is mediated by the selective gene activation of anabolic enzymes and increased ATP as the basis to activate multiple metabolic pathways without remarkable changes of substrate availability or feedback inhibition.
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PMID:Increased de novo purine synthesis by insulin through selective enzyme induction in primary cultured rat hepatocytes. 218 59

Imprinted maternal-allele-specific expression of the mouse insulin-like growth-factor type 2 receptor (Igf2r) gene depends on a 3.7-kb element named region 2, located in the second intron of the gene. Region 2 carries a maternal-allele-specific methylation imprint and contains an imprinted CpG island promoter (Air) that expresses a noncoding antisense RNA from the paternal inherited allele only. Here, we use transgenes to test the minimal requirements for imprinting of Air and to test if the action of region 2 is restricted to Igf2r. Transgenes up to 9 kb with Air as a single promoter are expressed but not imprinted. When coupled to the Igf2r CpG island promoter on a 44-kb transgene, Air was imprinted in one of three lines. However, Air on a 4.6-kb fragment is also imprinted in 2 of 14 lines when inserted in an intron of an adenine phosphoribosyltransferase (Aprt) transgene, and in one line, the imprinted methylation and expression of Air have been transferred onto the Aprt CpG island promoter. These data suggest that a dual CpG island promoter setting may facilitate Air imprinting as a short transgene and also show that Air can transfer imprinting onto other genes. However, for reliable Air imprinting, elements are necessary that are located outside a 44-kb region spanning the Air-Igf2r promoters.
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PMID:Investigation of elements sufficient to imprint the mouse Air promoter. 1143 57