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Gene Review

GPI  -  glucose-6-phosphate isomerase

Sus scrofa

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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


Biological context of GPI


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].


  1. Porcine malignant hyperthermia carrier detection and chromosomal assignment using a linked probe. Davies, W., Harbitz, I., Fries, R., Stranzinger, G., Hauge, J.G. Anim. Genet. (1988) [Pubmed]
  2. Genes specifying receptors for F18 fimbriated Escherichia coli, causing oedema disease and postweaning diarrhoea in pigs, map to chromosome 6. Vögeli, P., Bertschinger, H.U., Stamm, M., Stricker, C., Hagger, C., Fries, R., Rapacz, J., Stranzinger, G. Anim. Genet. (1996) [Pubmed]
  3. Detection of linkage between genetic markers and genes that affect growth and carcass traits in pigs. Clamp, P.A., Beever, J.E., Fernando, R.L., McLaren, D.G., Schook, L.B. J. Anim. Sci. (1992) [Pubmed]
  4. The neurotrophic factor neuroleukin is 90% homologous with phosphohexose isomerase. Chaput, M., Claes, V., Portetelle, D., Cludts, I., Cravador, A., Burny, A., Gras, H., Tartar, A. Nature (1988) [Pubmed]
  5. Inhibition of platelet integrin GPIIbIIIa prolongs survival of discordant cardiac xenografts. Candinas, D., Lesnikoski, B.A., Hancock, W.W., Otsu, I., Koyamada, N., Dalmasso, A.P., Robson, S.C., Bach, F.H. Transplantation (1996) [Pubmed]
  6. N-methylated analogs of Ac[Nle28,31]CCK(26-33): synthesis, activity, and receptor selectivity. Ron, D., Gilon, C., Hanani, M., Vromen, A., Selinger, Z., Chorev, M. J. Med. Chem. (1992) [Pubmed]
  7. Precise localization of the genes for glucose phosphate isomerase (GPI), calcium release channel (CRC), hormone-sensitive lipase (LIPE), and growth hormone (GH) in pigs, using nonradioactive in situ hybridization. Chowdhary, B.P., Thomsen, P.D., Harbitz, I., Landset, M., Gustavsson, I. Cytogenet. Cell Genet. (1994) [Pubmed]
  8. FISH on metaphase and interphase chromosomes demonstrates the physical order of the genes for GPI, CRC, and LIPE in pigs. Chowdhary, B.P., de la Sena, C., Harbitz, I., Eriksson, L., Gustavsson, I. Cytogenet. Cell Genet. (1995) [Pubmed]
  9. Localization on pig chromosome 6 of markers GPI, APOE, and ENO1, carried by human chromosomes 1 and 19, using in situ hybridization. Yerle, M., Gellin, J., Dalens, M., Galman, O. Cytogenet. Cell Genet. (1990) [Pubmed]
  10. Assignment of the porcine calcium release channel gene, a candidate for the malignant hyperthermia locus, to the 6p11----q21 segment of chromosome 6. Harbitz, I., Chowdhary, B., Thomsen, P.D., Davies, W., Kaufmann, U., Kran, S., Gustavsson, I., Christensen, K., Hauge, J.G. Genomics (1990) [Pubmed]
  11. Opioid agonist and antagonist bivalent ligands. The relationship between spacer length and selectivity at multiple opioid receptors. Portoghese, P.S., Larson, D.L., Sayre, L.M., Yim, C.B., Ronsisvalle, G., Tam, S.W., Takemori, A.E. J. Med. Chem. (1986) [Pubmed]
  12. Topographically designed analogues of [D-Pen,D-Pen5]enkephalin. Hruby, V.J., Toth, G., Gehrig, C.A., Kao, L.F., Knapp, R., Lui, G.K., Yamamura, H.I., Kramer, T.H., Davis, P., Burks, T.F. J. Med. Chem. (1991) [Pubmed]
  13. Interaction of phosphatidylinositolglycan(-peptides) with plasma membrane lipid rafts triggers insulin-mimetic signaling in rat adipocytes. Müller, G., Jung, C., Frick, W., Bandlow, W., Kramer, W. Arch. Biochem. Biophys. (2002) [Pubmed]
  14. Isolation of region-specific probes from pig chromosome 6 by coincidence cloning. Frengen, E., Thomsen, P.D., Schmitz, A., Frelat, G., Davies, W. Mamm. Genome (1994) [Pubmed]
  15. Localization of the glucose phosphate isomerase gene to the p12----q21 segment of chromosome 6 in pig by in situ hybridization. Chowdhary, B.P., Harbitz, I., Mäkinen, A., Davies, W., Gustavsson, I. Hereditas (1989) [Pubmed]
  16. Evidence of omega-conotoxin GV1A-sensitive Ca2+ channels in mammalian peripheral nerve terminals. Lundy, P.M., Frew, R. Eur. J. Pharmacol. (1988) [Pubmed]
  17. Purification and analysis of the neutral glycan moiety of glycosyl phosphatidylinositol from porcine thyroid cells. Sartelet, H., Petitfrere, E., Martiny, L., Haye, B. Biomed. Chromatogr. (1999) [Pubmed]
  18. Synthesis and biological activity in the GPI test of scyliorhinin I and its Val7 and Ile7 analogs. Rolka, K., Kupryszewski, G., Janas, P., Myszor, J., Herman, Z.S. Polish journal of pharmacology and pharmacy. (1992) [Pubmed]
  19. Tetraethylammonium and 4-aminopyridine enhancement of 5-HT3 receptor-mediated contraction of guinea pig ileum in vitro. Yuan, Y.M., Yang, H.H., Hu, G.Y. Zhongguo yao li xue bao = Acta pharmacologica Sinica. (1998) [Pubmed]
  20. Characterization of porcine and ovine Oesophagostomum spp. by isoenzymatic patterns and restriction-fragment-length polymorphisms (RFLPs). Cutillas, C., Guevara-Martínez, D., Oliveros, R., Arias, P., Guevara, D.C. Acta Trop. (1999) [Pubmed]
  21. Study of candidate genes for glycolytic potential of porcine skeletal muscle: identification and analysis of mutations, linkage and physical mapping and association with meat quality traits in pigs. Fontanesi, L., Davoli, R., Nanni Costa, L., Scotti, E., Russo, V. Cytogenet. Genome Res. (2003) [Pubmed]
  22. Design and synthesis of highly potent and selective cyclic dynorphin A analogues. Kawasaki, A.M., Knapp, R.J., Kramer, T.H., Wire, W.S., Vasquez, O.S., Yamamura, H.I., Burks, T.F., Hruby, V.J. J. Med. Chem. (1990) [Pubmed]
  23. Long-range mapping of the calcium release channel and glucosephosphate isomerase loci using pulsed-field gel electrophoresis. Frengen, E., Davies, W. Anim. Genet. (1995) [Pubmed]
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