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Query: UNIPROT:P06889 (Mol)
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PgiC, a complex gene with 23 coding exons and 22 intervening introns, encodes the cytosolic isozyme of phosphoglucose isomerase (EC 5.3.1.9) in higher plants. Here, we report RNA ligase-mediated rapid amplification of cDNA ends experiments that showed that PgiC in Clarkia (Onagraceae) and Arabidopsis thaliana has an intron in the 5' leader. Comparison of the EMBL accessions of the cDNA and genomic sequences showed that this is also the case in rice (Oryza sativa), suggesting that a leader intron is generally present in higher plant PgiC. The intron is bounded by consensus 5'-GT and AG-3' splice sites but showed alternative splicing in Clarkia, resulting in mature transcripts that differ by 8-19 nt in length. The intron is located 18 or 10 nt upstream of the start codon in Clarkia, 2 nt upstream in Arabidopsis, and 9 nt in rice. PgiC in Clarkia was duplicated before the divergence of the extant species, many of which have two expressed genes PgiC1 and PgiC2. Full-length transcripts of both genes identified the transcription start and made it possible to identify the leader intron and leader exon (between the transcription start and leader intron) from previously obtained genomic sequences of both genes in other Clarkia species. These data permit the comparison of evolution in the leader exon and intron with the exons and introns of the coding region, a topic that has not been studied previously. Both the leader exon and the leader intron resemble introns of the coding region in base substitution rate and accumulation of gaps. But the leader intron splice junctions are not strictly conserved in position as are those of the coding region introns. Also, in base composition, the leader intron resembles the other introns, whereas the leader exon more nearly resembles the coding exons. A difference in base composition between coding exons and flanking introns is known to be important for the recognition of splice sites. Thus, the marked difference in base composition between the leader exon and leader intron is probably maintained by selection despite a high rate of sequence divergence.
Mol Biol Evol 2002 Sep
PMID:The 5' leader of plant PgiC has an intron: the leader shows both the loss and maintenance of constraints compared with introns and exons in the coding region. 1220 Apr 88

Phosphoglucose isomerase (PGI; EC 5.3.1.9) is the second enzyme in glycolysis, where it catalyzes the isomerization of D-glucose-6-phosphate to D-fructose-6-phosphate. It is the same protein as autocrine motility factor, differentiation and maturation mediator, and neuroleukin. Here, we report a new X-ray crystal structure of rabbit PGI (rPGI) without ligands bound in its active site. The structure was solved at 1.8A resolution by isomorphous phasing with a previously solved X-ray crystal structure of the rPGI dimer containing 6-phosphogluconate in its active site. Comparison of the new structure to previously reported structures enables identification of conformational changes that occur during binding of substrate or inhibitor molecules. Ligand binding causes an induced fit of regions containing amino acid residues 209-215, 245-259 and 385-389. This conformational change differs from the change previously reported to occur between the ring-opening and isomerization steps, in which the helix containing residues 513-521 moves toward the bound substrate. Differences between the liganded and unliganded structures are limited to the region within and close to the active-site pocket.
J Mol Biol 2002 Oct 11
PMID:Conformational changes in phosphoglucose isomerase induced by ligand binding. 1236

Natural genetic variants at the phosphoglucose isomerase, PGI, gene differ in spatial patterning of their polymorphism among species complexes of Colias butterflies in North America. In both lowland and alpine complexes, molecular-functional properties of the polymorphic genotypes can be used to predict genotype-specific adult flight performances and resulting large genotypic differences in adult fitness components. In the lowland species complex, there is striking uniformity of PGI polymorph frequencies at a number of sites across the American West; this fits with earlier findings of strong, similar differences in fitness components over this range. In an alpine complex, Colias meadii shows similar uniformity of PGI frequencies within habitat types, either montane steppe or alpine tundra, over several hundred kilometres in the absence of dispersal. At the same time, large shifts (10-20%) in frequency of the most common alleles occur between steppe and tundra populations, whether these are isolated or, as in some cases, are in contact and exchange many dispersing adults each generation. Data on male mating success of common C. meadii PGI genotypes in steppe and tundra show heterozygote advantage in both habitat types, with shifts in relative homozygote disadvantage between habitats which are consistent with observed frequency differences. Nonadaptive explanations for this situation are rejected, and alternative, thermal-ecology-based adaptive hypotheses are proposed for later experimental test. These findings show that strong local selection may dominate dispersal as an evolutionary agent, whether or not dispersal is present, and that selection may often be the major force promoting 'cohesion' of species over long distances. This case offers new opportunities for integrating studies of molecular structure and function with ecological aspects of natural selection in the wild, both within and among species.
Mol Ecol 2003 May
PMID:Adaptation at specific loci. VII. Natural selection, dispersal and the diversity of molecular-functional variation patterns among butterfly species complexes (Colias: Lepidoptera, Pieridae). 1269 89

Adriamycin, which is widely used in the treatment of various neoplastic conditions, exerts toxic effects in several organs. Adriamycin nephrotoxicity has been recently documented in a variety of animal species. The present study was designed to investigate the effect of lipoic acid on the nephrotoxic potential of adriamycin. The study was carried out with adult male albino rats of Wistar strain. Test animals were divided into four groups of six rats each as follows: Group I (control) received only normal saline throughout the course of the experiment. Group II (ADR) received intravenous injections of adriamycin through the tail vein (1 mg kg(-1) body wt day(-1)) once a week for a period of 12 weeks. Group III (LA) received lipoic acid (35 mg kg(-1) body wt day(-1)) intraperitoneally once a week for a period of 12 weeks. Group IV (ADR + LA) received a single injection of lipoic acid intraperitoneally 24 h prior to the administration of adriamycin through the tail vein once a week for a period of 12 weeks. Intravenous injections of adriamycin resulted in decreased activities of the glycolytic enzymes; hexokinase, phosphoglucoisomerase, aldolase and lactate dehydrogenase in the rat renal tissue. The gluconeogenic enzymes, glucose-6-phosphatase and fructose-1,6-diphosphatase, showed a decline in their activities on adriamycin administration. The transmembrane enzymes namely the Na+,K+-ATPase, Ca2+-ATPase, Mg2+-ATPase and the brush-border enzyme alkaline phosphatase also showed a decrease in their activities. This decrease in the activities of ATPases and alkaline phosphatase suggests basolateral and brush-border membrane damage. Decreased activities of the TCA cycle enzymes isocitrate dehydrogenase, succinate dehydrogenase and malate dehydrogenase, suggest a loss in mitochondrial function and integrity. Nephrotoxicity was evident from the increased excretions of N-acetyl-beta-D-glucosaminidase and gamma-glutamyl transferase in the urine of adriamycin administered rats. These biochemical disturbances were effectively counteracted on pre-treatment with lipoic acid, which brought about an increase in the activities of glycolytic enzymes, ATPases and the TCA cycle enzymes. On the other hand, the gluconeogenic enzymes showed a further decrease in their activities on lipoic acid pretreatment. LA pretreatment also restored the activities of the urinary enzymes to normal. These observations shed light on the nephroprotective action of lipoic acid rendered against experimental aminoglycoside toxicity.
Mol Cell Biochem 2003 May
PMID:The influence of lipoic acid on adriamycin induced nephrotoxicity in rats. 1284 26

A mutational block in the early stages of the glycolytic pathway facilitates the degradation of the ptsG mRNA encoding the major glucose transporter IICBGlc in Escherichia coli. The degradation is RNase E dependent and is correlated with the accumulation of either glucose-6-P or fructose-6-P (Kimata et al., 2001, EMBO J 20: 3587-3595; Morita et al., 2003, J Biol Chem 278: 15608-15614). In this paper, we investigate additional physiological effects resulting from the accumulation of glucose-6-P caused by a mutation in pgi encoding phosphoglucose isomerase, focusing on changes in gene expression. The addition of glucose to the pgi strain caused significant growth inhibition, in particular in the mlc background. Cell growth then gradually resumed as the level of IICBGlc decreased. We found that the transcription of the cps operon, encoding a series of proteins responsible for the synthesis of colanic acid, was markedly but transiently induced under this metabolic stress. Both genetic and biochemical studies revealed that the metabolic stress induces cps transcription by activating the RcsC/YojN/RcsB signal transduction system. Overexpression of glucose-6-P dehydrogenase eliminated both growth inhibition and cps induction by reducing the glucose-6-P level. Mutations in genes responsible for the synthesis of glucose-1-P and/or dTDP-glucose eliminated the activation of the Rcs system by the metabolic stress. Taken together, we conclude that an increased synthesis of dTDP-glucose activates the Rcs phosphorelay system, presumably by affecting the synthesis of oligosaccharides for enterobacterial common antigen and O-antigen.
Mol Microbiol 2004 Feb
PMID:Metabolic block at early stages of the glycolytic pathway activates the Rcs phosphorelay system via increased synthesis of dTDP-glucose in Escherichia coli. 1476 84

This study aims at assessing the conversion of exogenous D-[1-13C]fructose, D-[2-13C]fructose or D-[6-13C]-fructose (10 mM) to 13C-enriched and either hydrogenated or deuterated D-glucose, L-lactate and L-alanine released by rat liver cells prepared from Goto-Kakizaki rats and incubated for 120 min in the presence of unlabelled D-glucose (also 10 mM) and D2O. The results of this study are relevant to the relative contribution of fructokinase and hexokinase isoenzyme to the phosphorylation of D-fructose, the capacity of D-glucose to confer to glucokinase positive cooperativity towards D-fructose, the circulation of D-fructose 6-phosphate in the pentose phosphate pathway, the regulation of the cytosolic NADD/NADH ratio, the respective fate of D-fructose-derived D-glyceraldehyde and dihydroxyacetone phosphate, the deuteration of fructose-derived glycolytic intermediates at the phosphoglucoisomerase, phosphomannoisomerase, enolase, pyruvate kinase and glutamate-alanine transaminase levels, and the unequal generation of L-[1-13C]lactate by cells exposed to D-[1-13C]fructose or D-[6-13C]fructose versus D-[2-13C]-fructose.
Int J Mol Med 2004 May
PMID:Metabolism of 13C-enriched D-fructose in hepatocytes from Goto-Kakizaki rats. 1506 73

It was recently proposed that alpha-D-glucose 6-phosphate may undergo enzyme-to-enzyme channelling between glucokinase and phosphoglucoisomerase in rat pancreatic islets. The present study aims at exploring whether a different situation prevails in cells deprived of glucokinase, namely in erythrocytes. At anomeric equilibrium, the ratio between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH was lower in rat erythrocytes incubated for 60 min at 4 degrees C in the presence of 2.8 mM, rather than 8.3 mM, D-glucose. This coincided with both a greater relative increase in beta-D-[5-3H]glucose, as compared to alpha-D-[5-3H]glucose, conversion to 3HOH and an increase in the beta/alpha ratio for 3HOH generation from D-[5-3H]glucose in response to an increase in the anomeric concentration from 2.8 to 8.3 mM, the suppression of the difference between the beta/alpha ratios for 3HOH generation from D-[2-3H]glucose and D-[5-3H]glucose in the erythrocytes incubated at 8.3 mM, as distinct from 2.8 mM, alpha- and beta-D-glucose, and a [2-3H]/[5-3H] ratio for 3HOH generation lower than unity in erythrocytes exposed to alpha-D-glucose but not significantly different from unity in the presence of beta-D-glucose. These findings emphasize the relevance of alpha-D-glucose 6-phosphate channelling between hexokinase and phosphoglucoisomerase as a determinant of the difference between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH, and reveal that the regulation of such a tunnelling process by the concentration of the D-glucose represents, in rat erythrocytes, a mirror image of that observed in rat pancreatic islets. The regulation of this process thus tightly depends on the identity of the hexokinase enzyme mainly responsible for the phosphorylation of D-glucose in distinct cell types.
Mol Cell Biochem 2004 Apr
PMID:Metabolism of tritiated D-glucose anomers in rat erythrocytes. 1512 13

Based on the measurement of 3HOH generation from the alpha- and beta-anomer of D-[2-3H]glucose and D-[5-3H] glucose by rat pancreatic islets, it was recently proposed that alpha-D-glucose 6-phosphate may undergo enzyme-to-enzyme channelling between hexokinase isoenzymes and phosphoglucoisomerase. Taking into account the results of such measurements, the present study aims at defining a model for the metabolism of alpha- and beta-D-glucose in islets exposed to 2.8 or 8.3 mM equilibrated D-glucose. It is proposed that, whilst keeping the activity of free phosphoglucoisomerase at its physiological value, all available experimental data can be adequately reproduced in a model in which all molecules of alpha-D-glucose 6-phosphate, whether unlabelled or tritiated on their C2 carbon atom, undergo, without isotopic discrimination, the postulated enzyme-to-enzyme channelling process. In such a model, the fractional intermolecular transfer of tritium at the phosphoglucoisomerase level amounts to 26%, suggesting that the intrinsic catalytic properties of the enzyme may be slightly different in the proposed metabolon than that prevailing for the unbound enzyme. These findings thus afford further support to the concept that alpha-D-glucose 6-phosphate, as distinct from beta-D-glucose 6-phosphate, is tunnelled, in rat pancreatic islets, in the sequence of reactions catalyzed by hexokinase isoenzymes, phosphoglucoisomerase and, possibly, phosphofructokinase.
Int J Mol Med 2004 Oct
PMID:Mathematical modelling of alpha- and beta-D-glucose metabolism in pancreatic islets exposed to equilibrated D-glucose. 1537 1

Pyrococcus furiosus phosphoglucose isomerase (PfPGI) is a metal-containing enzyme that catalyses the interconversion of glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P). The recent structure of PfPGI has confirmed the hypothesis that the enzyme belongs to the cupin superfamily and identified the position of the active site. This fold is distinct from the alphabetaalpha sandwich fold commonly seen in phosphoglucose isomerases (PGIs) that are found in bacteria, eukaryotes and some archaea. Whilst the mechanism of the latter family is thought to proceed through a cis-enediol intermediate, analysis of the structure of PfPGI in the presence of inhibitors has led to the suggestion that the mechanism of this enzyme involves the metal-dependent direct transfer of a hydride between C1 and C2 atoms of the substrate. To gain further insight in the reaction mechanism of PfPGI, the structures of the free enzyme and the complexes with the inhibitor, 5-phospho-d-arabinonate (5PAA) in the presence and absence of metal have been determined. Comparison of these structures with those of equivalent complexes of the eukaryotic PGIs reveals similarities at the active site in the disposition of possible catalytic residues. These include the presence of a glutamic acid residue, Glu97 in PfPGI, which occupies the same position relative to the inhibitor as that of the glutamate that is thought to function as the catalytic base in the eukaryal-type PGIs. These similarities suggest that aspects of the catalytic mechanisms of these two structurally unrelated PGIs may be similar and based on an enediol intermediate.
J Mol Biol 2004 Oct 22
PMID:The structures of inhibitor complexes of Pyrococcus furiosus phosphoglucose isomerase provide insights into substrate binding and catalysis. 1546 52

The anomeric specificity of D-glucose metabolism in intact hepatocytes remains a matter of debate. This issue was further investigated in the present study, which is based on the quantification of the alpha- and beta-anomers of the 13C-enriched isotopomers of D-glucose generated by rat liver cells exposed to either D-[1-13C] fructose or D-[2-13C] fructose in the presence of D2O. The D-[1-13C]glucose/D-[6-13C]glucose paired ratios found in the cells exposed to D-[1-13C] fructose and the D-[2-13C]glucose/D-[5-13C]glucose paired ratios found in the cells exposed to D-[2-13C] fructose yielded a paired beta/alpha ratio averaging (mean +/- S.E.M.) 79.3 +/- 6.1%. In the case of the isotopomers of D-glucose formed by gluconeogenesis, the D-[2-13C]glucose/D-[5-13C]glucose and D-[3-13C]glucose/D-[4-13C]glucose paired ratios found in cells exposed to D-[1-13C] fructose, as well as the D-[1-13C]glucose/D-[6-13C]glucose and D-[3-13C]glucose/D-[4-13C]glucose paired ratios found in cells exposed to D-[2-13C]fructose, yielded an alpha/beta paired ratio averaging 75.0 +/- 5.8%. Last, in the cells exposed to D-[2-13C]fructose, the beta/alpha ratio for the C2-deuterated isotopomers of D-[2-13C]glucose represented 78.9 +/- 3.7% of that for the C5-deuterated isotopomers of D-[5-13C]glucose. The three values representative of the anomeric specificity of D-glucose production by liver cells were not significantly different from one another, with an overall mean value of 76.9 +/- 3.6%. These findings unambiguously document that the anomeric specificity of phosphoglucoisomerase is operative in intact hepatocytes, resulting in a preferential output of the alpha-anomer of 13C-enriched D-glucose under the present experimental conditions.
Mol Cell Biochem 2004 Nov
PMID:Anomeric specificity of D-glucose production by rat hepatocytes. 1564 36


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