Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
 692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

About 79% of all the Japanese patients with adenine phosphoribosyltransferase (APRT) deficiency have been estimated to possess at least one APRT*J allele with a substitution of ACG for ATG at codon 136. We developed a non-radioactive method for diagnosing genotypes of this disease. Part of the genomic DNA including the mutation site of the APRT*J allele was amplified using polymerase chain reaction and the amplified product was dot-blotted onto nylon membranes and then hybridized with either APRT*J-specific or non-APRT*J-specific synthetic oligonucleotides labelled at the 5' termini with biotin in the presence of non-labelled competitive synthetic sequences. The temperature was gradually decreased during the hybridization. When competitive sequences were omitted, difference in the intensity of the hybridization between APRT*J-containing and non-containing samples was not sufficiently clear to differentiate the genotypes. When an excess amount of competitive sequences was added in addition to biotin-labelled oligonucleotides, this method effectively differentiated samples containing only APRT*J alleles from those containing only non-APRT*J alleles. The present method was also useful to differentiate samples with both APRT*J and non-APRT*J alleles from those having only either of the alleles. An equivalent procedure using competitive sequence for hybridization and gradually decreasing the temperature will be useful for detecting point mutations in other genes.
Clin Chim Acta 1991 Dec 16
PMID:Detection of the most common mutation of adenine phosphoribosyltransferase deficiency among Japanese by a non-radioactive method. 177 79

We examined the molecular basis of adenine phosphoribosyltransferase (APRT) deficiency in homozygous-deficient, identical twin brothers who were born to non-consanguineous German parents. DNA was isolated from blood, and the APRT gene was amplified by PCR, subcloned into M13, and sequenced completely. A single T insertion between bases 1831-1832 or 1832-1833 was identified. This alters the consensus sequence at the exon 4 - intron 4 spice donor site and leads to aberrant splicing. The same mutation has been described previously in two affected brothers from Belgium, and the Indianapolis group has also identified it in two other, unrelated Caucasian patients. Thus, this mutation may be a common cause of APRT deficiency in the Caucasian population.
Klin Wochenschr 1990 Dec 30
PMID:Identification of a splice mutation at the adenine phosphoribosyltransferase locus in a German family. 213

The mechanism by which S-adenosylmethionine (SAM) and adenosine (Ado) increase ATP levels in intact human erythrocytes in vitro has been compared. The use of erythrocytes from healthy controls and from subjects totally deficient in adenine phosphoribosyltransferase (APRT), plus inhibitors of adenosine kinase (AK) and adenosine deaminase (ADA) separately and together, has enabled us to demonstrate that this increment in ATP levels occurred via totally different metabolic routes. The results show that: (i) whilst the Ado-induced increment in ATP was AK dependent, that produced by SAM was independent of AK: and (ii) the SAM-induced increment in ATP was totally dependent on APRT and that some of the increment produced by Ado might also be APRT dependent. The above data are consistent with the metabolism of SAM to ATP by a route recently identified by us whereby ATP is formed from deoxyadenosine: namely binding to the enzyme S-adenosylhomocysteine hydrolase with subsequent release of adenine and further conversion to ATP via APRT.
Biochem Pharmacol 1990 Dec 15
PMID:S-adenosylmethionine increases erythrocyte ATP in vitro by a route independent of adenosine kinase. 226 Sep 86

A mouse adenine phosphoribosyltransferase (aprt) pseudogene that had previously been recovered from a BALB/c sperm DNA library possessed several unusual features. Its nucleotide sequence, like that of other processed pseudogenes, was colinear with its corresponding mRNA, but it was truncated at its 3' end and lacked a poly(A) tail. The pseudogene was 82% homologous with corresponding regions of the functional gene and had incurred mutations that included transitions, transversions, deletions, and a point insertion. Even though the pseudogene was truncated within the protein-coding region of the corresponding functional gene, it was flanked at both ends by 13-base-pair direct repeats. Curiously, the direct repeats exhibited homology to APRT mRNA at the site of pseudogene divergence. The pseudogene appeared to be common to BALB/c and A/J mice, but it was contained on a 3-kilobase EcoRI fragment in the former strain and a 4.5-kilobase EcoRI fragment in the latter. The BALB/c and apparently the A/J pseudogene both mapped to chromosome 8, which also contains the functional aprt gene. The DNA sequences immediately surrounding the pseudogene in the two strains appeared to be similar, suggesting that the BALB/c and A/J pseudogenes are allelic. However, DNA sequences more distal to the pseudogene in the two strains appeared to vary. Thus, the EcoRI polymorphism was not due to simple loss of an EcoRI site, but was more complex. The pattern of flanking restriction sites was different for each of several enzymes, consistent with extensive DNA rearrangement. Double digests of BALB/c and A/J genomic DNAs revealed complex polymorphisms on both sides of the pseudogene. The results were consistent with insertion, deletion, or other rearrangement of DNA sequences that flank the pseudogene and suggest that this region of mouse chromosome 8 may be a region active for mutation or recombination.
Mol Cell Biol 1986 Dec
PMID:An unusual adenine phosphoribosyltransferase pseudogene is syntenic with its functional gene and is flanked by highly polymorphic DNAs. 302 40

2,8-Dihydroxyadenine urolithiasis is caused by genetic deficiencies of adenine phosphoribosyl-transferase. This disease has occurred in a large number of Japanese patients and more than half of all families with this disease are only partially deficient in enzyme activities (Japanese type adenine phosphoribosyltransferase deficiency). To clarify the reasons for the preponderance of Japanese cases we sent questionnaires to 948 Japanese urological departments. The data thus obtained indicated that 76 families had 2,8-dihydroxyadenine lithiasis and of 51 families in which adenine phosphoribosyltransferase activities were assayed 76 per cent were only partially deficient in adenine phosphoribosyltransferase activities. The distribution of the 2,8-dihydroxyadenine families was roughly similar to that of the population in Japan and the rates of the Japanese type adenine phosphoribosyltransferase deficiency families were not significantly different among the various parts of Japan. These data indicate that the wide distribution of the unique mutant gene, APRT*J, that was created many years ago in a Japanese ancestor, explains at least in part the large number of 2,8-dihydroxyadenine lithiasis and adenine phosphoribosyltransferase deficiency families among the Japanese.
J Urol 1988 Dec
PMID:Distribution of patients with 2,8-dihydroxyadenine urolithiasis and adenine phosphoribosyltransferase deficiency in Japan. 276 81

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.
Br J Urol 1988 Dec
PMID:Adenine phosphoribosyltransferase deficiency: 2,8-dihydroxyadenine urolithiasis in a 48-year-old woman. 280 78

A screening method using high-performance liquid chromatography (HPLC) for the simultaneous detection of deficiencies of adenine phosphoribosyltransferase (APRT) and hypoxanthine phosphoribosyltransferase (HPRT) activities in human erythrocytes is described. Both enzyme reactions of APRT and HPRT in lysates treated with a charcoal-dextran were simultaneously carried out in the same reaction tube and the enzyme activities were determined by measuring the increases in absorbance at 260 nm of adenosine and inosine converted from adenosine-5'-monophosphate and inosine-5'-monophosphate with alkaline phosphatase. Adenosine and inosine were separated from adenine and hypoxanthine by a reversed-phase column. The method could detect 1% of normal APRT activity and 0.3% of normal HPRT activity. The within-run coefficients of variation for APRT and HPRT activities were 3.2 and 3.4%, respectively.
Clin Chim Acta 1987 Dec
PMID:Screening for adenine and hypoxanthine phosphoribosyltransferase deficiencies in human erythrocytes by high-performance liquid chromatography. 343 62

We have used a rapid in vivo recombinational method to clone and completely sequence 34 UV-induced mutants at the adenine phosphoribosyltransferase (APRT) locus of Chinese hamster ovary cells. Among the mutants recovered, 26 were single base substitutions including 17 G.C----A.T transitions and a single A.T----G.C transition. Three of the 4 possible transversions accounted for the remaining 8 mutations. The G.C----T.A transversion was not recovered. Six tandem double or closely neighboring double-base substitutions, one double mutation consisting of a G.C----T.A transversion and an adjacent frameshift, as well as one single frameshift mutation were also recovered. UV-induced mutation appears to be targeted to dipyrimidine sites with only two exceptions. These include two double mutations where only one of the base substitutions occurred at a dipyrimidine site. The observed specificity of UV-light-induced mutations at the APRT locus is consistent with the argument that G.C----A.T transitions result primarily from the (6-4) pyrimidine pyrimidone lesion. A striking resemblance in the distribution of UV-induced mutants and a collection of 30 spontaneous mutants identified recently in our laboratory was noted. Both share a common strong site of multiple occurrence and a considerable degree of overlap with respect to site specificity. We speculate therefore that DNA context plays a significant role in mutation fixation in mammalian cells.
Proc Natl Acad Sci U S A 1987 Dec
PMID:The specificity of UV-induced mutations at an endogenous locus in mammalian cells. 348 May 33

Exogenous adenine strongly inhibited mitogen-stimulated transformation, cytoplasmic immunoglobulin production, and natural killer activity of human mononuclear leukocytes at the high concentration of 1.0 mM. These inhibitions by adenine were not due to cytotoxicity, because the viability of cultured cells was not affected by adenine up to 1.0 mM. As the magnitude of inhibition by adenine of these in vitro immunological functions was similar in normal and adenine phosphoribosyltransferase-deficient cells, its inhibition was not mediated by corresponding nucleotides. Adenine at the concentration of 0.1 mM caused 50% inhibition of cytoplasmic immunoglobulin production without alternating cell proliferation or viability. This suggests that an appropriate concentration of adenine may inhibit the differentiation of B cells to plasma cells rather than affecting cell proliferation. Understanding the mechanisms of adenine inhibition may lead to new approaches for the regulation of immune responses.
Immunopharmacology 1985 Dec
PMID:Inhibition by adenine of in vitro immunological functions of normal and adenine phosphoribosyltransferase-deficient human lymphocytes. 383 54

Genomic libraries of Plasmodium falciparum were constructed in the pBR322 plasmid. Using the DNA-mediated gene transfer technique, the genomic libraries were introduced into tissue-cultured mouse cells lacking the enzyme adenine phosphoribosyltransferase. Following selection for the adenine phosphoribosyltransferse phenotype, several colonies were isolated. All clones were shown to possess adenine phosphoribosyltransferase activity and pBR322 sequences. In addition, the Km value of adenine phosphoribosyltransferase (for adenine) from a transformant was found to be identical to that from P. falciparum. These results indicate that the adenine phosphoribosyltransferase gene of P. falciparum was successfully cloned and expressed in a mammalian system.
Exp Parasitol 1985 Dec
PMID:Plasmodium falciparum: expression of the adenine phosphoribosyltransferase gene in mouse L cells. 390 33


<< Previous 1 2 3 4 5 Next >>