Postnatal Behaviour of Guanase Activity in Rat Tissues

Nardiello, S; Galanti, B; Russo, M.; Guarino, F

doi:10.1159/000458600

Cited by 6 publications

(3 citation statements)

References 3 publications

(5 reference statements)

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“…GAH catalyzes the hydrolytic deamination of guanine, yielding xanthine and ammonium, and is considered to be involved in a major pathway for producing uric acid (30). As consistent with our findings, GAH was shown to be abundant in brain, and its activity was detected in both nuclear and cytosolic fractions (31)(32)(33), although the biological significance has been largely unknown.…”

Section: Discussionsupporting

confidence: 90%

A Novel NE-dlg/SAP102-associated Protein, p51-nedasin, Related to the Amidohydrolase Superfamily, Interferes with the Association between NE-dlg/SAP102 and N-Methyl-d-aspartate Receptor

Kuwahara¹,

Araki²,

Makino³

et al. 1999

Journal of Biological Chemistry

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The membrane-associated guanylate kinase proteins have been known to interact various membrane receptors with their N-terminal segments designated the PDZ domains and to cluster these receptors at the target site of the cell membrane. NE-dlg/SAP102, a neuronal and endocrine tissue-specific MAGUK family protein, was found to be expressed in both dendrites and cell bodies in neuronal cells. Although NE-dlg/SAP102 localized at dendrites was shown to interact with N-methyl-D-aspartate receptor 2B via the PDZ domains to compose postsynaptic density, the binding proteins existing in the cell body of the neuron are still unknown. Here we report the isolation of a novel NE-dlg/SAP102-associated protein, p51-nedasin. Nedasin has a significant homology with amidohydrolase superfamily proteins and shows identical sequences to a recently identified protein that has guanine aminohydrolase activity. Nedasin has four alternative splice variants (S, V1, V2, and V3) that exhibited different C-terminal structures. NE-dlg/ SAP102 is shown to interact with only the S form of nedasin which is predominantly expressed in brain. The expression of nedasin in neuronal cells increases in parallel with the progress of synaptogenesis and is mainly detected in cell bodies where it co-localizes with NE-dlg/ SAP102. Furthermore, nedasin interferes with the association between NE-dlg/SAP102 and NMDA receptor 2B in vitro. These findings suggest that alternative splicing of nedasin may play a role in the formation and/or structural change in synapses during neuronal development by modifying clustering of neurotransmitter receptors at the synaptic sites.At the sites of cell-cell contacts of epithelial cells or the synaptic junctions of neuronal cells, several membrane receptors and channels are clustered into multiprotein complexes linked to the cytoskeleton via interactions of their C-terminal cytoplasmic tails with a novel protein family called membraneassociated guanylate kinase homologues (MAGUK) 1 (1). The MAGUK family proteins contain three distinct domains as follows: an N-terminal segment comprised of one or three copies of an 80 -90-amino acid motif called the PDZ (PSD-95/Dlg/ ZO-1) domain, an src homology 3 (SH3) domain, and a region with high similarity to guanylate kinases (GK) (2, 3). The PDZ domain is utilized as a module for interacting with the Cterminal Xaa-(Ser/Thr)-Xaa-Val (X(S/T)XV) motif of various proteins and generating multiprotein complexes (4, 5).Each MAGUK protein is thought to perform a distinct function depending upon its tissue distribution, cellular localization, and associated molecules. For instance, PSD-95/SAP90, which is one of the MAGUK proteins, is predominantly expressed in the brain and localizes at the postsynaptic membrane and presynaptic axon terminals of inhibitory neurons (6 -8). PSD-95/SAP90 binds to the cytoplasmic tail of both Shaker-type voltage-gated K ϩ channels and the 2B subunit of N-methyl-D-aspartate (NMDA)-type glutamate receptors (7, 9 -11). PSD-95/SAP90 expressed in neuronal cells is therefo...

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Section: Discussionsupporting

confidence: 90%

A Novel NE-dlg/SAP102-associated Protein, p51-nedasin, Related to the Amidohydrolase Superfamily, Interferes with the Association between NE-dlg/SAP102 and N-Methyl-d-aspartate Receptor

Kuwahara¹,

Araki²,

Makino³

et al. 1999

Journal of Biological Chemistry

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“…It is a cytosolic enzyme with a K, of 5-10 pA4 for guanine. Its activity is especially high in the brain, liver, myocardium, and kidney (Nardiello et al, 1978). In the brain, its distribution is uneven, with highest activities in the thalamus and cerebral hemispheres and lacking activity in the cerebellum, medulla, and spinal cord (Dawson,197 1).…”

Section: Discussionmentioning

confidence: 99%

Metabolism of Guanine and Guanine Nucleotides in Primary Rat Neuronal Cultures

Brosh

Sperling²,

Dantziger³

et al. 1992

Journal of Neurochemistry

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The metabolic fate of guanine and of guanine ribonucleotides (GuRNs) in cultured rat neurons was studied using labeled guanine. 8-Aminoguanosine (8-AGuo), an inhibitor of purine nucleoside phosphorylase, was used to clarify the pathways of GMP degradation, and mycophenolic acid, an inhibitor of IMP dehydrogenase, was used to assess the flux from IMP to GMP and, indirectly, the activity of the guanine nucleotide cycle (GMP----IMP----XMP----GMP). The main metabolic fate of guanine in the neurons was deamination to xanthine, but significant incorporation of guanine into GuRNs, at a rate of approximately 8.5-13.1% of that of the deamination, was also demonstrated. The turnover rate of GuRNs was fast (loss of 80% of the radioactivity of the prelabeled pool in 22 h), reflecting synthesis of nucleic acids (32.8% of the loss in radioactivity) and degradation to xanthine, guanine, hypoxanthine, guanosine, and inosine (49.3, 4.3, 4.1, 1.1, and 0.5% of the loss, respectively). Of the radioactivity in GuRNs, 7.9% was shifted to adenine nucleotides. The accumulation of label in xanthine indicates (in the absence of xanthine oxidase) that the main degradative pathway from GMP is that to xanthine through guanosine and guanine. The use of 8-AGuo confirmed this pathway but indicated the operation of an additional, relatively slower degradative pathway, that from GMP through IMP to inosine and hypoxanthine. Hypoxanthine was incorporated mainly into adenine nucleotide (91.5%), but a significant proportion (6%) was found in GuRNs.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…There are greater than 50-fold differences in guanine deaminase among different regions of the mouse brain; the cerebral cortex and amygdala have the highest activity (4), whereas there is essentially no activity in the cerebellum of the mouse or cat (4,5). There are greater than 10-fold increases in the level of expression of guanine deaminase in the liver, kidney, and brain during the 40-day postnatal development of the rat (6), and alterations in embryonic expression have also been characterized (7). In the adult mouse, fractional increases in brain and liver enzyme activity occur in response to intraperitoneal administration of a bolus of guanine (8).…”

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confidence: 99%

Cloning and Characterization of Human Guanine Deaminase

Yuan

Bin

McKay

et al. 1999

Journal of Biological Chemistry

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Mouse erythrocyte guanine deaminase has been purified to homogeneity. The native enzyme was dimeric, being comprised of two identical subunits of approximately 50,000 Da. The protein sequence was obtained from five cyanogen bromide cleavage products giving sequences ranging from 12 to 25 amino acids in length and corresponding to 99 residues. Basic Local Alignment Search Tool (BLAST) analysis of expressed sequence databases enabled the retrieval of a human expressed sequence tag cDNA clone highly homologous to one of the mouse peptide sequences. The presumed coding region of this clone was used to screen a human kidney cDNA library and secondarily to polymerase chain reaction-amplify the full-length coding sequence of the human brain cDNA corresponding to an open reading frame of 1365 nucleotides and encoding a protein of 51,040 Da. Comparison of the mouse peptide sequences with the inferred human protein sequence revealed 88 of 99 residues to be identical. The human coding sequence of the putative enzyme was subcloned into the bacterial expression vector pMAL-c2, expressed, purified, and characterized as having guanine deaminase activity with a K m for guanine of 9.5 ؎ 1.7 M. The protein shares a 9-residue motif with other aminohydrolases and amidohydrolases (PGX[VI]DXH[TVI]H) that has been shown to be ligated with heavy metal ions, commonly zinc. The purified recombinant guanine deaminase was found to contain approximately 1 atom of zinc per 51-kDa monomer.Guanine deaminase (guanine aminohydrolase, EC 3.5.4.3) catalyzes the hydrolytic deamination of guanine. By producing xanthine and ammonia, this reaction irreversibly eliminates the guanine base from further reutilization as a guanylate nucleotide in mammals. The product xanthine is a substrate for xanthine oxidase in the production of uric acid. Although it is an enzyme of purine catabolism, guanine deaminase is not ubiquitously expressed and exhibits a general absence in lymphoid tissues and variable expression elsewhere (1, 2). The highest levels of expression were found in the proximal section of the small intestine of the mouse (3). There are greater than 50-fold differences in guanine deaminase among different regions of the mouse brain; the cerebral cortex and amygdala have the highest activity (4), whereas there is essentially no activity in the cerebellum of the mouse or cat (4, 5). There are greater than 10-fold increases in the level of expression of guanine deaminase in the liver, kidney, and brain during the 40-day postnatal development of the rat (6), and alterations in embryonic expression have also been characterized (7). In the adult mouse, fractional increases in brain and liver enzyme activity occur in response to intraperitoneal administration of a bolus of guanine (8). The tissue-specific expression and the developmental and induced changes in expression suggest a potential role for guanine deaminase in the regulation of the guanine nucleotide pool. Cellular GTP has an important role not only in specific enzyme reactions and protein synth...

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Postnatal Behaviour of Guanase Activity in Rat Tissues

Cited by 6 publications

References 3 publications

A Novel NE-dlg/SAP102-associated Protein, p51-nedasin, Related to the Amidohydrolase Superfamily, Interferes with the Association between NE-dlg/SAP102 and N-Methyl-d-aspartate Receptor

A Novel NE-dlg/SAP102-associated Protein, p51-nedasin, Related to the Amidohydrolase Superfamily, Interferes with the Association between NE-dlg/SAP102 and N-Methyl-d-aspartate Receptor

Metabolism of Guanine and Guanine Nucleotides in Primary Rat Neuronal Cultures

Cloning and Characterization of Human Guanine Deaminase

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