Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A gene for tryptophanyl-tRNA synthetase (EC 6.1.1.2), the enzyme which attaches tryptophan to its tRNA, has previously been assigned to human chromosome 14 by analysis of man-mouse somatic cell hybrids. We report here a method for the electrophoretic separation of Chinese hamster and human tryptophanyl-tRNA synthetases and its application to a series of independently derived Chinese hamster-human hybrids in which part of the human chromosome 14 has been translocated to the human X chromosome. When this derivative der (X),t(X;14) (Xqter leads to Xp22::14q21 leads to 14qter) chromosome carrying the human gene for hypoxanthine-guanine phosphoribosyltransferase was selected for and against in cell hybrid lines by the appropriate selective conditions, the human tryptophanyl-tRNA synthetase activity was found to segregate concordantly. These results provide additional confirmation for the assignment of the tryptophanyl-tRNA synthetase gene to human chromosome 14 and define its intrachromosomal location in the region 14q21 leads to 14qter. Our findings indicate that the genes for tryptophanyl-tRNA synthetase and for ribosomal RNA are not closely linked on chromosome 14.
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PMID:Intrachromosomal gene mapping in man: the gene for tryptophyl-tRNA synthetase maps in region q21 leads to qter of chromosome 14. 56 85

The behaviour of human cells arrested in mitosis can be severely perturbed so as to generate numerous small minisegregants containing very few chromosomes. These cells can be separated according to size and DNA content and fused with intact cells. In this paper we describe the production and some properties of proliferating cell hybrids generated by fusion of human minisegregant cells derived from a HeLa strain with mouse A9 cells deficient in hypoxanthine phosphoribosyltransferase (HPRT, EC 2.4.2.8). The hybrids were shown to contain up to 10 human chromosomes including a single X. Independently derived hybrid clones were quantitatively characterized and compared with the parental phenotypes with respect to HPRT. Human isozymes of each of the 3 enzymes HPRT, glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and phosphoglycerate kinase (EC 2,7.2.3) were found. Tests to evaluate both structure and function of HPRT were utilized. The specific activity of HPRT of more than 10 hybrids tested was approximately 10% that of the HeLa parent. Structural characterization of HPRT from hybrid cells as evidenced by heat inactivation and electrophoretic mobility results in a 'human-like' phenotype. Functional characterization of parental HPRT results in kinetic constants for cofactor and substrate which do not permit distinction of human and of human and mouse enzymes; HPRT from the minisegregant hybrids had normal kinetic constants. The reduced specific activity of HPRT in the hybrids is discussed in terms of the inability of the mouse environment to regulate the full expression of the human structural gene.
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PMID:Transfer of human chromosomes via human minisegregant cells into mouse cells and the quantitation of the expression of hypoxanthine phosphoribosyltransferase in the hybrids. 56 87

Human and mouse hypoxanthine-guanine phosphoribosyltransferase subunits combine to form an active heteropolymer. Dimers form the basic subunit structure of the enzymes, yet the dimers can readily associate to form tetramers. The equilibrium between dimers and tetramers is significantly influenced by the ionic strength of the enzyme solvent.
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PMID:Human and mouse hypoxanthine-guanine phosphoribosyltransferase: dimers and tetramers. 56 62

The availability of systems which permit the selective elimination of marsupial cells from fused cultures is an essential requirement for the production of marsupial X eutherian somatic cell hybrids. Such hybrids have particular advantages for genetic studies of mammalian cells. We describe the isolation and characterization of several drug-resistant marsupial cell strains. We have selected strains resistant to concentrations of 10 micrograms/ml of the purine analogues 8-azaguanine and 6-thioguanine. Several of these strains were found to be deficient in the enzyme hypoxanthine phosphoribosyltransferase and consequently sensitive to hypoxanthine-aminopterin-thymidine (HAT) selective medium. We have also isolated marsupial cell strains resistant to concentrations of 22 micrograms/ml of the thymidine analogue 5-bromodeoxyuridine. These strains were thymidine kinase deficient and HAT sensitive. Drug resistance was a stable characteristic maintained for many generations in the absence of the drug. However, inhibition of growth of these drug-resistant strains was strongly density dependent, a factor that caused difficulties in the selection of hybrids. We have also developed selective systems which exploit differences between marsupial and eutherian cells in sensitivity to growth in ouabain, and in adhesiveness and other growth properties. Marsupial cells were found to be naturally much more sensitive to ouabain than rodent cells, a phenomenon that should be useful in the selection of marsupial X rodent cellular hybrids. We discuss a number of difficulties associated with the derivation and use of variant marsupial cell strains.
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PMID:Fusion and hybridization of marsupial and eutherian cells. V. Development of selective systems. 56 74

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 mutagenicity of six heterocylic nitrogen mustards (ICR compounds) has been determined in a cultured mammalian cell system by use of resistance to the purine analog 6-thioguanine to select for mutation induction at the hypoxanthine-guanine phosphoribosyltransferase locus in Chinese hamster ovary cells. The six compounds tested are ICR 191, 170, 292, 372, 191-OH, and 170-OH. The first four contain a single 2-chloroethyl group (nitrogen half-mustard) on the side chain and are mutagenic, with the tertiary amine types (170 and 292) 3 to 5 times more mutagenic than the secondary amine types (191 and 372). The remaining two compounds (191-OH and 170-OH) are not mutagenic, indicating that the 2-chloroethyl group is needed for mutation induction.
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PMID:Mutagenicity of heterocyclic nitrogen mustards (ICR compounds) in cultured mammalian cells. 62 55

Hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) has been purified 23,000-fold from normal human erythrocytes. The purification includes affinity chromatography on a GMP column. The subunit molecular weight of the enzyme obtained from this purification is 24,000. The finding of four protein species after cross-linkage of the highly purified enzyme with dimethylsuberimidate, dimethyladipimidate, and glutaraldehyde suggests that the enzyme may exist in the native state as a tetramer.
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PMID:Human hypoxanthine-guanine phosphoribosyltransferase. Evidence for tetrameric structure. 65 26

A now 45-year-old man with marked chronic tophous gout and recurrent nephrolithiasis has been followed for 12 years. First gouty symptoms appeared at age 18. Uric-acid reducing treatment freed the patient of symptoms, and bony and soft-tissue tophi in part regressed. The early onset and high urinary uric-acid excretion indicated increased uric-acid production. Decreased activity of the enzyme hypo-xanthine-guanine-phosphoribosyl transferase was demonstrated to be the cause of the hyperuricaemia, which led to an excessive purine synthesis. An almost complete loss of activity of this enzyme is the basis of the Lesch-Nyhan syndrome. In the described patient all of the neurological and behavioural disorders of the Lesch-Nyhan syndrome were absent. A pheochromocytoma was found to be the cause of malignant hypertension, which had been present for many years.
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PMID:[Juvenile gout with decreased activity of hypoxanthine-guanine-phosphoribosyl transferase and pheochromocytoma: partial persistence of tophi despite uric-acid reducing treatment for 12 years (author's transl)]. 66 12

The behavioural symptoms in a 10-year-old boy with Lesch-Nyhan syndrome were effectively ameliorated by the behavior therapy techniques of systematic desensitization and extinction. Therapy was undertaken in a highly controlled environment. The hypothesis that the self-destructive behaviours in this syndrome were voluntary and maintained through continuous reinforcement was confirmed. Characteristic biting and other maladaptive behaviours were extinguished. Over a period of time it was possible to remove all the physical restraints previously used to prevent the boy injuring himself. During treatment his anxiety, associated with phobic reaction to being unrestrained, was reduced by nitrous oxide. At 1 1/2 years follow-up the boy continues to be symptom-free. He attends a special class at school and is learning to walk with crutches. It is emphasied that a trained and experienced therapist and a controlled environment are essential for the success of this form of behaviour therapy, and the dangers inherent in this method of treatment are discussed.
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PMID:Behavior therapy for a child with Lesch-Nyhan syndrome. 66 67

A steady state kinetic study of the hypoxanthine-guanine phosphoribosyltransferase-catalyzed reaction in the forward and the reverse directions was carried out. The results obtained favor a sequential mechanism where the monomagnesium complexes of IMP and PPi bind to the enzyme in a rapid equilibrium random fashion while products must dissociate from the enzyme in ordered sequence, first the purine base and then the magnesium complex(es) of P-Rib-PP.
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PMID:Human hypoxanthine-guanine phosphoribosyltransferase. Steady state kinetics of the forward and reverse reactions. 68 38


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