[Clinical and biochemical studies of glucosephosphate isomerase of normal human erythrocytes and in glucosephosphate isomerase deficiency].
Explore the source record for details and available documents.
Adult↗
SEARCH · Search PubMed
Results for “Glucosephosphates”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Behaviour of the glycolytic system of rat brain and kidney in vivo after inhibition of the glucosephosphate isomerase. I. Kinetic studies on rat brain glucosephosphate isomerase.
Explore the source record for details and available documents.
Animals↗
Mild purification procedure and subunit structure of glucosephosphate isomerase from baker's yeast.
A mild procedure for the purification of glucosephosphate isomerase from baker's yeast (Saccharomyces cerevisiae) is reported. The purified enzyme was homogeneous and did not contain charge isomers as shown by polyacrylamide gel electrophoresis as well as DEAE-Sepharose column chromatography. Its molecular weight determined by gel filtration and sucrose density gradient centrifugation was approximately 120 000, which agreed with that of the enzyme in the crude extract as well as that of the renatured enzyme. Gel filtration in 6M guanidine/HCl as well as acrylamide gel electrophoresis of sodium dodecyl sulfate denatured glucosephosphate isomerase showed one single peak and gave a subunit molecular weight of 60 000. Cross-linking patterns obtained with yeast glucosephosphate isomerase after treatment with dimethyl suberimidate resulted in the appearance of dimers as the largest-linked product of the enzyme subunit. After dissociation the enzyme can readily be reassociated and renatured with a yield of maximum 73% and a pseudo first order rate constant of 0.12 min-1 at 25 degrees C.
Chemical Phenomena↗
Sugar synthesis in Leptospira. I. Presence of glucosephosphate isomerase.
The presence of glucosephosphate isomerase, one of the key enzymes in carbohydrate metabolism, was confirmed for the first time in the cell-free extract of Leptospira biflexa. The glucosephosphate isomerase of L. biflexa was heat-labile and its optimum pH was about 8.5. The enzyme showed an optimal temperature of about 45 C but was more stable at 30 C. Km value of the enzyme was 5.6 X 10(-3)M. The activity of the enzyme was inhibited by the inhibitor, 6-phosphogluconate. From this study, the presence of a metabolic pathway, the phosphogluconate pathway, other than non-oxidative pentose phosphate pathway presented by Baseman and Cox was suggested.
Citric Acid Cycle↗
Clinical symptoms and biochemical properties of three new glucosephosphate isomerase variants.
Glucosephosphate isomerase deficiency as the cause of macrocytic congenital nonspherocytic hemolytic anemia is described in three unrelated families. The biochemical properties of the variant glucosephosphate isomerases indicate that the patients have new variants, designated as GPI Kiel, GPI Hamburg, and GPI Homburg. The severity of the clinical symptoms depended on the amount of residual GPI activity and the biochemical properties of the variant enzyme. Thus the patient with GPI Kiel (34% residual activity) whose variant GPI was slightly unstable showed a mild chronic hemolytic anemia. The patient with GPI Homburg (7% residual activity) whose variant enzyme was stable and had a reduced specific activity, suffered from severe congenital hemolytic anemia and neuromuscular symptoms. Due to the special properties of GPI Homburg, we assume that both the hematological and neuromuscular symptoms of the patient with GPI Homburg are caused by his GPI deficiency. The twins with GPI Hamburg (27% residual activity) had a distinctly unstable variant enzyme and had suffered from hemolytic crises since birth. Only GPI Homburg showed an altered electrophoretic mobility and an increased affinity for fructose-6-phosphate. The other two variants had normal values.
Adolescent↗
Biochemical genetics of a new glucosephosphate isomerase allele (Gpi-1c) from wild mice.
We have found a new allele at the structural locus for glucosephosphate isomerase (called Gpi-1c) in a population of wild mice. The Gpi-1c allele codes for an enzyme of greater cathodal electrophoretic mobility than either the Gpi-1a or Gpi-1b alleles found in the wild and in the SM/J and C57BL/6J inbred strains. Mice homozygous for Gpi-1c have erythrocyte enzyme activity reduced to 33% of normal levels, altered pH profile, lowered heat stability, and normal Km's when compared with SM/J and C57BL/6J mice. The activity of the enzyme in brain, liver, and kidney is not so markedly lowered, although the electrophoretic mobility, pH profile, and heat stability are altered in these tissues. Deficiencies of erythrocyte glucosephosphate isomerase in man, to this level, can cause severe hemolytic anemia. Homozygotes for Gpi-1c show only mild hematological symptoms. The frequency of Gpi-1c in wild populations of mice is discussed and the occurrence of a further rare allele Gpi-1d is reported.
Alleles↗
A biochemical comparison of glucosephosphate isomerase isozymes from Trypanosoma cruzi.
The glucosephosphate isomerase (D-glucose-6-phosphate Ketol-isomerase, EC 5.3.1.9) isozymes of Trypanosoma cruzi were characterized with respect to their native and subunit molecular size, isoelectric point and in vitro thermostability. The molecular weight data are consistent with a dimeric enzyme structure. The apparent native and subunit size homogeneity and differences in pI values imply that the electrophoretic mobility differences of isozymes in native gels are determined by their molecular charge. Minor differences in peptide maps indicate the existence of some heterogeneity in the primary structure of the isozymes. The stability of triple-banded glucosephosphate isomerase electrophoretic profiles was confirmed, supporting the view that these phenotypes represent non-interconvertible enzyme species.
Animals↗
Glucosephosphate isomerase deficiency in a Dutch family.
A mentally retarded girl with severe hemolytic anemia due to glucosephosphate isomerase deficiency is described. The deficiency was detected in erythrocytes, leukocytes, thrombocytes, liver and muscle tissues. Besides the glucosephosphate isomerase deficiency, a glutathione instability of unknown origin was found in the erythrocytes of the propositus.
Anemia, Hemolytic, Congenital↗
An immunofluorescence procedure for the tissue localization of glucosephosphate isomerase.
Anti-glucosephosphate isomerase antibodies have been used to reveal the presence of the glycolytic and gluconeogenic enzyme, glucosephosphate isomerase (GPI) in mouse tissues by an indirect immunofluorescence technique. The enzyme was localized in 6-micron sections from tissues embedded in paraffin. GPI was observed in the sarcoplasm of skeletal muscle, all hepatocytes of the liver, and in the granulosa cells and oocytes of growing ovarian follicles. The immunofluorescence procedure circumvents the problems associated with the conventional localization of GPI by histochemistry and appears to be a more sensitive procedure for the detection of low concentrations of GPI, as demonstrated by the staining of the ovarian follicles.
Animals↗
Isolation and characterization of tissue-specific isozymes of glucosephosphate isomerase from catfish and conger.
In teleosts glucosephosphate isomerase exists as two tissue-specific isozymes. Most tissues contain the more acidic liver-type isozyme, while white muscle contains the more basic isozyme; and a few tissues contain both the liver- and muscle-type isozymes as well as a hybird. The isozymes were isolated from catfish liver and muscle and from conger muscle and shown to be homogeneous by polyacrylamide gel electrophoresis, isoelectric focusing, analytical ultracentrifugation, and rechromatography. Both isozymes are of molecular weight 132,000 (S020,w = 7.0 S) and composed of two subunits of Mr approximately 65,000. The muscle and liver isozymes were shown to have distinct isoelectric points (catfish liver = 6.2; muscle = 7.0) and amino acid compositions. Tryptic peptide maps, after S-carboxymethylation and carbamylation, revealed several distinct differences in the primary structures of the isozymes. Although the isozymes could also be distinguished on the basis of their stabilities, most of their basic catalytic properties were found to be similar. A conger was obtained which was heterozygous for the variant allele at the muscle-glucosephosphate isomerase locus. A comparison of the variant conger muscle isozyme with the wild type revealed a single altered peptide, suggesting a point mutation. The structure-function studies, as well as the genetic studies, clearly establish that the two types of isozymes are of independent genetic origin.
Alleles↗
Concurrent measurements of carcinoembryonic antigen, glucosephosphate isomerase, gamma-glutamyltransferase, and lactate dehydrogenase in malignant, normal adult, and fetal colon tissues.
Carcinoembryonic antigen and activities of glucosephosphate isomerase (EC 5.3.1.9), gamma-glutamyltransferase (EC 2.3.2.2), and lactate dehydrogenase (EC 1.1.1.27) were measured in aqueous extracts of fetal, normal adult, and malignant human colon tissues. Fetal colon, as well as primary and metastatic colon tumor tissue, showed higher activities of these analytes than did normal adult human colon. Liver metastases of colon cancer gave the highest values, normal adult human colon the lowest. Statistically, these differences were more striking in the case of carcinoembryonic antigen and glucosephosphate isomerase than for gamma-glutamyltransferase or lactate dehydrogenase. In contrast to the other markers, gamma-glutamyltransferase activity was lower in fetal organs than in normal adult colon and colon tumors. These results are consistent with earlier observations that activities of these markers are significantly increased in the blood of patients with metastatic colon cancer.
Adult↗
Affinity labeling and characterization of the active site histidine of glucosephosphate isomerase. Sequence homology with triosephosphate isomerase.
N-Bromoacetylethanolamine phosphate was found to act as a specific affinity label for the active center of glucosephosphate isomerase. The inactivation process followed pseudo-first order kinetics, was irreversible and exhibited rate saturation kinetics with minimal half-lives of inactivation of 4.5 and 6.3 min for the enzyme isolated from human placenta and rabbit muscle, respectively. The pH dependence of the inactivation process closely paralleled the pH dependence of the overall catalytic process with pKa values at pH 6.4 and 9.0. The stoichiometry of labeling of either enzyme, as determined with N-bromo[14C2]acetylethanolamine phosphate, was 1 eq of the affinity label/subunit of enzyme. After acid hydrolysis and amino acid analysis of the radioactive affinity-labeled human enzyme, only radioactive 3-carboxymethyl histidine was found. In the case of the rabbit enzyme, the only radioactive derivative obtained was 1-carboxymethyl histidine. Active site tryptic peptides were isolated by solvent extraction, thin layer peptide fingerprinting, and ion exchange chromatography before and after removal of the phosphate from the active site peptide. Amino acid analysis of the labeled peptides from the two species were very similar. Using high sensitivty methods for sequence analysis, the primary structure of the active site was established as Val-Leu-His-Ala-Glu-Asn-Val-Asp (Gly,Thr,Ser) Glu-Ile (Thr-Gly-His-Lys-Glx)-Tyr-Phe. Apparent sequence homology between the catalytic center of glucosephosphate isomerase and triosephosphate isomerase suggest that the two enzymes may have evolved from a common ancestral gene.
Affinity Labels↗
Combined erythrocyte glucosephosphate isomerase (GPI) and glucose-6-phosphate dehydrogenase (G6PD) deficiency in an Italian family.
A severe hemolytic crisis was observed in a 5-year-old boy of Italian origin. Analysis of his hemolysate revealed a hemizygous deficiency of glucose-6-phosphate dehydrogenase (G6PD) and a heterozygous deficiency of glucosephosphate isomerase (GPI). According to the literature this is the fourth family with a combined deficiency of these two enzymes located on different chromosomes. Only the G6PD deficiency seems to be responsible for the hemolytic crisis.
Anemia, Hemolytic↗
A new mutant erythrocyte glucosephosphate isomerase (GPI) associated with GSH abnormality.
A case of congenital nonspherocytic haemolytic anaemia associated with a new abnormal glucosephosphate isomerase (GPI), GSH (reduced glutathione) deficiency, and instability and altered carbohydrate membrane composition is reported. The only functional abnormality of the mutant enzyme seems to be a marked instability to heat, urea, and guanidine-HCl. Family studies suggest that the propositus is doubly heterozygous for a maternal gene producing an inactive enzyme and a paternal gene responsible for a structural alteration causing marked lability of the coded enzyme. Experiments of incubation of normal GPI and the propositus's GPI with oxidizing and reducing agents seem to indicate that the abnormality resides in the SH groups of the mutant GPI.
Adolescent↗
Glucosephosphate isomerase (GPI) deficiency mutations associated with hereditary nonspherocytic hemolytic anemia (HNSHA).
Five unrelated patients with hereditary glucosephosphate isomerase (GPI) deficiency resulting in nonspherocytic hemolytic anemia were studied. Three new mutations were found in the coding region of the GPI gene: two patients were heterozygous for 223 A-->G (R75G) and 898 G-->C(R300P), respectively and one was homozygous for 1415G-->A(R472H). Surprisingly, 2 previously reported mutations, 286 C-->T and 1039 C-->T, were found in 2 and 3 patients respectively. Until now only 4 of 18 GPI mutations had been found more than once in unrelated patients and these 4 in only 2 patients each. Eleven of the 20 known point mutations have occurred at CpG "hot spots" and the 286 C-->T and 1039 C-->T are among these. The 489 G/A polymorphism in the GPI coding region was used to demonstrate unequivocally that the 1039 C-->T mutation occurred in both haplotypes and therefore probably originated more than once. Because no common GPI mutation has been found we suggest that heterozygosity for GPI confers little if any selective advantage.
Adult↗
Characterization of a porcine glucosephosphate isomerase-processed pseudogene at chromosome 1q1.6-1.7.
A porcine glucosephosphate isomerase-processed pseudogene has been isolated and sequenced. The pseudogene has several base substitutions as well as an insertion and deletions, and is 83% homologous to the corresponding cDNA. It contains an intervening sequence of 565 bp, is truncated at the 3' end, and is flanked by direct repeats of seven nucleotides. Fluorescent in situ hybridization to porcine metaphase chromosomes localized the processed pseudogene to Chromosome (Chr) 1q1.6-1.7. A (GT)14(AT)15 microsatellite was detected close to the processed pseudogene.
Animals↗
Generalised glucosephosphate isomerase (GPI) deficiency causing haemolytic anaemia, neuromuscular symptoms and impairment of granulocytic function: a new syndrome due to a new stable GPI variant with diminished specific activity (GPI Homburg).
A new glucosephosphate isomerase (GPI) variant is described which is characterised by very low specific activity in erythrocytes, granulocytes and muscle tissue, nearly normal stability, normal kinetic properties and a decreased electrophoretic mobility. The propositus suffers from a complex syndrome involving erythrocytes (congenital haemolytic anaemia), granulocytes (decreased production of superoxide anion and reduced bactericidal activity in vitro) and the neuromuscular system (myopathy, mental retardation). It is suggested that the clinical syndrome results from generalised GPI deficiency due to a decreased specific activity of the variant enzyme, which cannot be compensated by an increase of de-novo synthesis of GPI protein even in cells exhibiting active protein synthesis such as granulocytes and muscle cells.
Adolescent↗
Glucosephosphate isomerase deficiency, a new variant in a Dutch family. Case report.
The clinical course and the biochemical findings are reported from a patient suffering from glucosephosphate isomerase (G.P.I EC 5.3.1.9) deficiency type Nijmegen. This disorder decleares itself as a non-spherocytic hemolytic anemia, presenting in the neonatal period. In the patient hemolysis was of the same degree during the years. However, trivial infections could often trigger an increase in hemolysis requiring treatment by blood transfusions. Enzyme studies revealed that the GPI deficiency in this patient was caused by a double heterozygous state for two different GPI deficient alleles. The presence of one of these deficient alleles in the proband's parents and grandparents, was not accompanied by any sign of hemolysis, as for instance a shortened red-cell survival.
Alleles↗