Disease relevance of GPI

• In pigs, the gene for glucosephosphate isomerase (GPI) is linked to the halothane (HAL) gene which is responsible for malignant hyperthermia (MH) [1].
• Linkage was demonstrated between the locus for F18 E. coli receptors and the loci S, RYR1, GPI, EAH, A1BG and PGD (Z > 20) [2].
• Pigs that inherited the GPI A allele from the sire had a 22-g higher daily live weight gain postweaning and reached 103 kg live weight in 2.6 fewer days than did pigs that inherited the GPI B allele (P less than .05), indicative of the presence of gene(s) that affect rate of gain linked to the GPI locus [3].

High impact information on GPI

• We have cloned the gene for pig muscle phosphohexose isomerase (PHI) (EC 5.3.1.9) which catalyses the conversion of glucose-6-phosphate to fructose-6-phosphate, an obligatory step in glycolysis, and determined its amino-acid sequence [4].
• Immunohistologic studies of HAR showed little effect of GPI 562 on platelet aggregation or activation and no effect on fibrin deposition [5].
• However, the combination of high-dose GPI 562 and CVF resulted in a significant decrease in intragraft platelet aggregation, P-selectin expression, and leukocyte infiltration compared with CVF alone [5].
• Similarly, whereas low-dose GPI 562 failed to prolong graft survival, high-dose GPI 562 showed a statistically significant increase in graft survival in both HAR and DXR groups [5].
• The bioassays employed were the guinea pig gallbladder (GPGB), stomach (GPS), and ileum (GPI) [6].

Biological context of GPI

• Fluorescence in situ hybridization (FISH) was applied, using genomic DNA clones, to precisely localize the genes for GPI, CRC, LIPE, and GH on pig chromosomes [7].
• A single copy DNA probe, designated GPI8R, has been isolated from a pig genomic library using a porcine GPI cDNA probe [1].
• FISH on metaphase and interphase chromosomes demonstrates the physical order of the genes for GPI, CRC, and LIPE in pigs [8].
• Localization on pig chromosome 6 of markers GPI, APOE, and ENO1, carried by human chromosomes 1 and 19, using in situ hybridization [9].
• We demonstrate synteny of the genes for CRC and GPI using somatic cell hybrid lines, and assign the CRC gene to chromosome 6p11----q21 by in situ hybridization [10].

Anatomical context of GPI

• The oxymorphamine bivalent ligands (1-8) behaved as mu agonists on the electrically stimulated guinea pig ileum longitudinal muscle preparation (GPI) [11].
• The potency and selectivity (delta vs mu opioid receptor) were evaluated by radioreceptor binding assays in the rat brain using [3H]CTOP (mu ligand) and [3H]DPDPE (delta ligand) and by bioassay with mouse vas deferens (MVD, delta receptor assay) and guinea pig ileum (GPI, mu receptor assay) [12].
• In isolated rat adipocytes, PIG(-P) induce the redistribution of GPI proteins from hcDIGs to low-cholesterol-containing DIGs (lcDIGs) and concomitantly provoke insulin-mimetic signaling and metabolic action [13].
• Coincidence cloning is a technique that permits the isolation of sequences common to two independent sources of complex DNA, and this method has been used to isolate a set of probes from a region of porcine Chromosome (Chr) 6 containing the loci for glucosephosphate isomerase (GPI) and the skeletal muscle calcium release channel (CRC) [14].
• The phosphoinositolglycan(-peptide) (PIG-P) portion of glycosylphosphatidylinositol-anchored plasma membrane (GPI) proteins or synthetic PIG(-P) molecules interact with proteinaceous binding sites which are located in high-cholesterol-containing detergent/carbonate-insoluble glycolipid-enriched raft domains (hcDIGs) of the plasma membrane [13].

Associations of GPI with chemical compounds

• The glucose phosphate isomerase (GPI) locus is closely linked to the halothane sensitivity locus in pig [15].
• On the other hand, in the bioassay systems, [(2S,3S)-beta-Me-p-NO2Phe4]DPDPE (5) is more potent than DPDPE and 8800-fold selective for the MVD (delta receptor) vs the GPI (mu receptor), making it the most highly selective ligand in this series for the delta opioid receptor on the basis of these bioassays [12].
• The 1,4-dihydropyridine VSCC antagonist (-) 202-791 (0.1-1.0 microM) inhibited the GPI twitch height, reduced contractions to exogenous ACh, but failed to affect ACh release [16].
• Next, successive chemical treatments allowed us to remove the neutral glycan moiety of thyroidal GPI, and its composition was obtained by gas chromatography [17].
• Synthesis and biological activity in the GPI test of scyliorhinin I and its Val7 and Ile7 analogs [18].

Regulatory relationships of GPI

• (2) Both TEA 0.05-0.5 mmol.L-1 and 4-AP 1-10 mumol.L-1 enhanced GPI contractions induced by the selective 5-HT3 receptor agonists 2-methyl-5-HT in concentration-dependent manners [19].

Other interactions of GPI

• The GPI and LIPE genes, which are closely linked to the CRC gene, were also mapped to the same band (6q12), using genomic lambda clones [7].
• In man, ENO1-PGD and APOE-GPI constitute two syntenic groups situated on different chromosomes (1 and 19, respectively) [9].
• Og showed identical G6PD, GPI and MDH isoenzymatic pattern as Od [20].
• Allele frequencies were analyzed in seven different pig breeds for these loci and for a polymorphism already described for GPI and for three polymorphic sites already reported at the PRKAG3 locus (T30N, G52S and I199V) [21].
• On the other hand, [Cys8,Cys13]Dyn A1-13-NH2 and [D-Cys8,D-Cys13]Dyn A1-13-NH2 (5) display high kappa potencies and selectivities at the peripheral (GPI) but not at the central (GPB) kappa opioid receptor [22].

Analytical, diagnostic and therapeutic context of GPI

• We therefore tested the effects of a specific GPIIbIIIa antagonist (SDZ GPI 562) during xenograft rejection [5].
• A protocol is described for the isolation and purification of free GPI using differential polarity of lipids and sequential thin layer chromatography [17].
• Long range restriction maps of the calcium release channel (CRC) and glucosephosphate isomerase (GPI) loci have been constructed using pulsed field electrophoresis, Southern blotting and CRC- and GPI-specific probes [23].
• METHODS: GPI contractions were recorded with a chart recorder through isometric transducers [19].

References