Disease relevance of GNPDA1

• Recombinant GPI-anchored HLA-A2.1 (HLA-A2.1-GPI/beta 2m) was used as a protein transfer vehicle to deliver a hepatitis B virus antigenic peptide to the surfaces of cytotoxic T cell targets [1].
• Survival of Helicobacter pylori From complement lysis by binding of GPI-anchored protectin (CD59) [2].
• A knock-out model of paroxysmal nocturnal hemoglobinuria: Pig-a(-) hematopoiesis is reconstituted following intercellular transfer of GPI-anchored proteins [3].
• Type B antibodies recognize other parts of beta2-GPI and are not associated with thrombosis [4].
• METHODS: Six human affinity-purified polyclonal anti-beta 2 GPI IgG and 2 IgM monoclonal antibodies (MAb) were obtained from patients with the antiphospholipid syndrome [5].

Psychiatry related information on GNPDA1

• In one, patients with moderately severe Parkinson's disease showed no overall improvement in fine motor skills following 6 months of treatment by the neuroimmunophilin GPI 1485 [6].
• Symptoms and signs differ in many respects from those generally observed in GPI deficiency, as mental retardation, drug sensitivity and increased susceptibility to infections were present [7].

High impact information on GNPDA1

• Nanoscale organization of multiple GPI-anchored proteins in living cell membranes [8].
• Compartmentalized signaling by GPI-anchored ephrin-A5 requires the Fyn tyrosine kinase to regulate cellular adhesion [9].
• Vanin-1, a novel GPI-linked perivascular molecule involved in thymus homing [10].
• Autoantibodies to GPI and creatine kinase in RA [11].
• In addition, discordant expression of GPI-linked molecules in individual cells is not restricted to PMN since DAF+/CD14- monocytes were observed in one PNH patient [12].

Chemical compound and disease context of GNPDA1

• Erythrocytes that do not express GPI-linked proteins, obtained from patients with paroxysmal nocturnal hemoglobinuria (PNH), release between 10% and 50% of the quantity of vesicles as normal cells in response to the Ca2+ ionophore A23187 [13].
• Glycosphingolipids are not essential for formation of detergent-resistant membrane rafts in melanoma cells. methyl-beta-cyclodextrin does not affect cell surface transport of a GPI-anchored protein [14].
• Oscillin, an extracellular, Ca2+-binding glycoprotein essential for the gliding motility of cyanobacteria [15].
• Systemic administration of GPI 15427, a novel poly(ADP-ribose) polymerase-1 inhibitor, increases the antitumor activity of temozolomide against intracranial melanoma, glioma, lymphoma [16].
• We wanted to examine whether increased levels of antibodies to negatively-charged phospholipids (cardiolipin), to phospholipid-binding plasma proteins beta2-GPI and prothrombin and to oxidised low-density lipoprotein (LDL) were associated with risk of deep venous thrombosis or pulmonary embolism in subjects with no previous thrombosis [17].

Biological context of GNPDA1

• The genomic structure of the human glucosamine-6-phosphate deaminase has been mapped and the gene was localized by fluorescence in situ hybridization (FISH) to chromosome 5q31 [18].
• The human Oscillin gene (HGMW-approved symbol GNPI) spans 12.4 kb and consists of eight exons [19].
• A hamster sperm-derived protein (Oscillin) with high similarity to bacterial GNPI has been proved to be capable of inducing calcium oscillation in eggs at fertilization [20].
• From the cDNA library of human dendritic cells (DC), we isolated a novel full-length cDNA encoding a 276-amino acid-residue protein that shares high homology with human GNPI/Oscillin [20].
• GNPI/Oscillin was supposed to be an important factor in starting embryonic development [20].

Anatomical context of GNPDA1

• Heterologous expression of the human testis 33 kDa protein produced a glucosamine-6-phosphate deaminase activity [18].
• Glucosamine 6-phosphate deaminase in normal human erythrocytes [21].
• In situ hybridization and immunohistochemistry localize GNPDA selectively to tissues with high energy requirements such as the apical zone of transporting epithelia in the proximal convoluted tubules of the kidney and the small intestine; to neurons (but not glia) and especially to nerve terminals in the brain; and to motile sperm [22].
• Molecularly cloned mammalian glucosamine-6-phosphate deaminase localizes to transporting epithelium and lacks oscillin activity [22].
• Oscillin was identified from hamster sperm as a factor responsible for oocyte calcium oscillations [19].

Associations of GNPDA1 with chemical compounds

• Glucosamine-6-phosphate deaminase (EC 3.5.99.6) is an allosteric enzyme that catalyzes the reversible conversion of D-glucosamine-6-phosphate into D-fructose-6-phosphate and ammonium [23].
• Like GNPI, the recombinant GNPI2 has been proved to have the enzymatic activity to catalyze the conversion of GNP to fructose-6-phosphate [20].
• Since GNPDA is the sole enzyme linking hexosamine systems with glycolytic pathways, we propose that it provides a source of energy in the form of phosphosugar derived from the catabolism of hexosamines found in glycoproteins, glycolipids, and sialic acid-containing macromolecules [22].
• GPI-deficient erythrocytes incubated with glucose in the medium showed an accentuation of membrane protein aggregate formation; however, this was almost completely reversed by the addition of adenine and inosine to the incubation medium or by the use of fructose, the intermediate just distal to the "block" in glycolysis, as the sole substrate [24].
• ATP and reduced glutathione levels in the GPI-deficient erythrocytes incubated with glucose were similar to that found in the low and high reticulocyte controls [24].

Other interactions of GNPDA1

• However, intracellular levels of N-acetylglucosamine-6-phosphate deacetylase and glucosamine-6-phosphate deaminase were markedly higher in S. mutans grown on glucose and GlcNAc than in S. sobrinus: 34 and 398 and 8 and 17 nmol of NADPH formed per mi per mg of protein for S. mutans and S. sobrinus, respectively [25].

Analytical, diagnostic and therapeutic context of GNPDA1

• Sequence analysis of the hamster sperm 33 kDa protein indicated no similarity to any known cell signalling molecule, however, it displayed extensive homology with a bacterial glucosamine-6-phosphate deaminase [18].
• Northern blot analysis indicated that the tissue distribution of GNPI2 mRNA is different from that of human GNPI or Oscillin mRNA [20].
• The concentration of GPI-related antigen was as reduced as the GPI enzymatic activity, and the defect was not improved by any treatment (cross-incubation of red cells or treatment of the hemolysate by SH reagents); the residual enzyme had a normal stability to heat, and a normal electrophoretic and electrofocusing pattern [26].
• Digestion of platelet membrane glycoproteins (GP(s] with chymotrypsin demonstrated that upon removal of GPI, RIPA was absent, CIPA retained and the CoI-PAR was progressive inhibition, with no enhancement [27].
• The reactivity of monoclonal aCL with various PLs, with DNA, and with beta 2-GPI was examined by enzyme-linked immunosorbent assay (ELISA) [28].

References