The Experts below are selected from a list of 102 Experts worldwide ranked by ideXlab platform
Fernando Climent - One of the best experts on this subject based on the ideXlab platform.
-
Phosphoglycerate mutase 2 3 bisPhosphoglycerate phosphatase creatine kinase and enolase activity and isoenzymes in breast carcinoma
British Journal of Cancer, 2000Co-Authors: N Durany, Fernando Climent, J Joseph, O M Jimenez, P L Fernandez, F Rivera, José CarrerasAbstract:We have compared the levels of Phosphoglycerate mutase (EC 5.4.2.1), 2,3-bisPhosphoglycerate phosphatase (EC 3.1.3.13), creatine kinase (EC 2.7.3.2) and enolase (EC 4.2.1.11) activities and the distribution of their isoenzymes in normal breast tissue and in breast carcinoma. Tumour tissue had higher Phosphoglycerate mutase and enolase activity than normal tissue. Creatine kinase activity was higher in seven out of 12 tumours. In contrast 2,3-bisPhosphoglycerate phosphatase activity was lower. Phosphoglycerate mutase, enolase and 2,3-bisPhosphoglycerate phosphatase presented greater changes in the oestrogen receptor-negative/progesterone receptor-negative breast carcinomas than in the steroid receptor-positive tumours. Determined by electrophoresis, type BB Phosphoglycerate mutase, type BB creatine kinase and αα-enolase were the major isoenzymes detected in normal breast tissue. Types αγ and γγ enolase, types MB and MM Phosphoglycerate mutase were detected in much lower proportions. In tumours a decrease of Phosphoglycerate mutase isoenzymes possessing M-type subunit and some increase of enolase isoenzymes possessing γ-type subunit was observed. No detectable change was observed in the creatine kinase phenotype. © 2000 Cancer Research Campaign
-
Thyroid hormone stimulates Phosphoglycerate mutase activity and isozyme transition in rat muscle tissues.
Life sciences, 1994Co-Authors: Manel Esteller, Jesús M. Ureña, José Carreras, Isabelle Martelly, Fernando ClimentAbstract:Triiodothyronine (T3) increases Phosphoglycerate mutase (PGAM) specific activity in rat skeletal and cardiac muscles. This increase is concomitant with an increase in the proportion of Phosphoglycerate mutase isozymes which contain type-M subunit. Propylthiouracil (PTU), an anti-hormone, not only decreases Phosphoglycerate mutase activity with respect to control rats, but also decreases the total M subunit contents. In liver, which only possesses type-B subunit Phosphoglycerate mutase, none of the effects were detected.
-
Phosphoglycerate mutase activity and mRNA levels during germination of maize embryos
Plant Science, 1993Co-Authors: Xavier Graña, Cristina Broceño, Judit Garriga, Pablo Pérez De La Ossa, Fernando ClimentAbstract:Abstract Phosphoglycerate mutase activity and mRNA levels during maize embryo germination were studied. Enzyme levels, activity and mRNA were found to be markedly increased during germination although in dry embryos Phosphoglycerate mutase was detected in the absence of mRNA. The results here reported demonstrate that the enzyme was present in dry embryos but new synthesis of the Phosphoglycerate mutase was required to permit the progress of germination.
-
Nuclear location of Phosphoglycerate mutase BB isozyme in rat tissues.
Histochemistry, 1992Co-Authors: Gustavo Egea, Jesús M. Ureña, José Carreras, Xavier Graña, J. Marsal, Fernando ClimentAbstract:We have previously reported (Urena et al. Eur. J. Cell Biol. 1990) that in skeletal muscle, type MM Phosphoglycerate mutase isozyme is present in the nucleus as well as in the cytosol. To determine whether type BB Phosphoglycerate mutase isozyme is also present in nucleus, the subcellular location of this isozyme was studied in different rat tissues by cell fractionation and immunogold techniques. With the aid of high affinity-purified anti-Phosphoglycerate mutase BB isozyme antibodies, the isozyme was located in the nucleus of neuronal, astroglial and liver cells but not in the nucleus of oligodendroglial and endothelial cells. Biochemical studies on purified nuclear fractions also demonstrated the presence of Phosphoglycerate mutase activity in the nucleus. Both immunocytochemical and biochemical techniques showed that nuclear Phosphoglycerate mutase-specific activity depended on the type of cell.
José Carreras - One of the best experts on this subject based on the ideXlab platform.
-
Phosphoglycerate mutase 2 3 bisPhosphoglycerate phosphatase creatine kinase and enolase activity and isoenzymes in breast carcinoma
British Journal of Cancer, 2000Co-Authors: N Durany, Fernando Climent, J Joseph, O M Jimenez, P L Fernandez, F Rivera, José CarrerasAbstract:We have compared the levels of Phosphoglycerate mutase (EC 5.4.2.1), 2,3-bisPhosphoglycerate phosphatase (EC 3.1.3.13), creatine kinase (EC 2.7.3.2) and enolase (EC 4.2.1.11) activities and the distribution of their isoenzymes in normal breast tissue and in breast carcinoma. Tumour tissue had higher Phosphoglycerate mutase and enolase activity than normal tissue. Creatine kinase activity was higher in seven out of 12 tumours. In contrast 2,3-bisPhosphoglycerate phosphatase activity was lower. Phosphoglycerate mutase, enolase and 2,3-bisPhosphoglycerate phosphatase presented greater changes in the oestrogen receptor-negative/progesterone receptor-negative breast carcinomas than in the steroid receptor-positive tumours. Determined by electrophoresis, type BB Phosphoglycerate mutase, type BB creatine kinase and αα-enolase were the major isoenzymes detected in normal breast tissue. Types αγ and γγ enolase, types MB and MM Phosphoglycerate mutase were detected in much lower proportions. In tumours a decrease of Phosphoglycerate mutase isoenzymes possessing M-type subunit and some increase of enolase isoenzymes possessing γ-type subunit was observed. No detectable change was observed in the creatine kinase phenotype. © 2000 Cancer Research Campaign
-
Distribution of Phosphoglycerate mutase isozymes in rat, rabbit and human tissues
Comparative biochemistry and physiology. Part B Biochemistry & molecular biology, 1996Co-Authors: N Durany, José CarrerasAbstract:The distribution of Phosphoglycerate mutase isozymes (types MM, MB and BB) in rat, rabbit and human tissues has been studied by electrophoresis on cellulose acetate and by highly-resolutive ion exchange chromatography. In the three species, muscle is the tissue with higher Phosphoglycerate mutase activity. Heart is the only tissue with the three Phosphoglycerate mutase isozymes in substantial amounts. Skeletal muscle contains mostly type MM isozyme and the other tissues possess almost exclusively type BB isozyme. Even in the presence of inhibitors, adenylate kinase can interfere with the staining reactions when large samples are analyzed and a long period of incubation is required.
-
Thyroid hormone stimulates Phosphoglycerate mutase activity and isozyme transition in rat muscle tissues.
Life sciences, 1994Co-Authors: Manel Esteller, Jesús M. Ureña, José Carreras, Isabelle Martelly, Fernando ClimentAbstract:Triiodothyronine (T3) increases Phosphoglycerate mutase (PGAM) specific activity in rat skeletal and cardiac muscles. This increase is concomitant with an increase in the proportion of Phosphoglycerate mutase isozymes which contain type-M subunit. Propylthiouracil (PTU), an anti-hormone, not only decreases Phosphoglycerate mutase activity with respect to control rats, but also decreases the total M subunit contents. In liver, which only possesses type-B subunit Phosphoglycerate mutase, none of the effects were detected.
-
Nuclear location of Phosphoglycerate mutase BB isozyme in rat tissues.
Histochemistry, 1992Co-Authors: Gustavo Egea, Jesús M. Ureña, José Carreras, Xavier Graña, J. Marsal, Fernando ClimentAbstract:We have previously reported (Urena et al. Eur. J. Cell Biol. 1990) that in skeletal muscle, type MM Phosphoglycerate mutase isozyme is present in the nucleus as well as in the cytosol. To determine whether type BB Phosphoglycerate mutase isozyme is also present in nucleus, the subcellular location of this isozyme was studied in different rat tissues by cell fractionation and immunogold techniques. With the aid of high affinity-purified anti-Phosphoglycerate mutase BB isozyme antibodies, the isozyme was located in the nucleus of neuronal, astroglial and liver cells but not in the nucleus of oligodendroglial and endothelial cells. Biochemical studies on purified nuclear fractions also demonstrated the presence of Phosphoglycerate mutase activity in the nucleus. Both immunocytochemical and biochemical techniques showed that nuclear Phosphoglycerate mutase-specific activity depended on the type of cell.
Mariette Robbi - One of the best experts on this subject based on the ideXlab platform.
-
Cloning, sequencing and expression of rat liver 3-Phosphoglycerate dehydrogenase.
Biochemical Journal, 1997Co-Authors: Younes Achouri, Mark H. Rider, Emile Van Schaftingen, Mariette RobbiAbstract:Rat liver d-3-Phosphoglycerate dehydrogenase was purified to homogeneity and digested with trypsin, and the sequences of two peptides were determined. This sequence information was used to screen a rat hepatoma cDNA library. Among 11 positive clones, two covered the whole coding sequence. The deduced amino acid sequence (533 residues; Mr 56493) shared closer similarity with Bacillus subtilis 3-Phosphoglycerate dehydrogenase than with the enzymes from Escherichia coli, Haemophilus influenzae and Saccharomyces cerevisiae. In all cases the similarity was most apparent in the substrate- and NAD+-binding domains, and low or insignificant in the C-terminal domain. A corresponding 2.1 kb mRNA was present in rat tissues including kidney, brain and testis, whatever the dietary status, and also in livers of animals fed a protein-free, carbohydrate-rich diet, but not in livers of control rats, suggesting transcriptional regulation. The full-length rat 3-Phosphoglycerate dehydrogenase was expressed in E. coli and purified. The recombinant enzyme and the protein purified from liver displayed hyperbolic kinetics with respect to 3-Phosphoglycerate, NAD+ and NADH, but substrate inhibition by 3-phosphohydroxypyruvate was observed; this inhibition was antagonized by salts. Similar properties were observed with a truncated form of 3-Phosphoglycerate dehydrogenase lacking the C-terminal domain, indicating that the latter is not implicated in substrate inhibition or in salt effects. By contrast with the bacterial enzyme, rat 3-Phosphoglycerate dehydrogenase did not catalyse the reduction of 2-oxoglutarate, indicating that this enzyme is not involved in human D- or L-hydroxyglutaric aciduria.
Yibin Kang - One of the best experts on this subject based on the ideXlab platform.
-
bisPhosphoglycerate mutase controls serine pathway flux via 3 Phosphoglycerate
Nature Chemical Biology, 2017Co-Authors: Rob C Oslund, Michael Haugbro, Jungmin Kee, Mark Esposito, Yael David, Boyuan Wang, David H Perlman, Yibin KangAbstract:Lower glycolysis involves a series of reversible reactions, which interconvert intermediates that also feed anabolic pathways. 3-Phosphoglycerate (3-PG) is an abundant lower glycolytic intermediate that feeds serine biosynthesis via the enzyme Phosphoglycerate dehydrogenase, which is genomically amplified in several cancers. Phosphoglycerate mutase 1 (PGAM1) catalyzes the isomerization of 3-PG into the downstream glycolytic intermediate 2-Phosphoglycerate (2-PG). PGAM1 needs to be histidine phosphorylated to become catalytically active. We show that the primary PGAM1 histidine phosphate donor is 2,3-bisPhosphoglycerate (2,3-BPG), which is made from the glycolytic intermediate 1,3-bisPhosphoglycerate (1,3-BPG) by bisPhosphoglycerate mutase (BPGM). When BPGM is knocked out, 1,3-BPG can directly phosphorylate PGAM1. In this case, PGAM1 phosphorylation and activity are decreased, but nevertheless sufficient to maintain normal glycolytic flux and cellular growth rate. 3-PG, however, accumulates, leading to increased serine synthesis. Thus, one biological function of BPGM is controlling glycolytic intermediate levels and thereby serine biosynthetic flux.
-
Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth
Cancer Cell, 2012Co-Authors: Taro Hitosugi, Lu Zhou, Heebum Kang, Changliang Shan, Liang Zhang, Tinglei Gu, Masa Aleckovic, Gary Leroy, Yibin KangAbstract:It is unclear how cancer cells coordinate glycolysis and biosynthesis to support rapidly growing tumors. We found that the glycolytic enzyme Phosphoglycerate mutase 1 (PGAM1), commonly upregulated in human cancers due to loss of TP53, contributes to biosynthesis regulation in part by controlling intracellular levels of its substrate, 3-Phosphoglycerate (3-PG), and product, 2-Phosphoglycerate (2-PG). 3-PG binds to and inhibits 6-phosphogluconate dehydrogenase in the oxidative pentose phosphate pathway (PPP), while 2-PG activates 3-Phosphoglycerate dehydrogenase to provide feedback control of 3-PG levels. Inhibition of PGAM1 by shRNA or a small molecule inhibitor PGMI-004A results in increased 3-PG and decreased 2-PG levels in cancer cells, leading to significantly decreased glycolysis, PPP flux and biosynthesis, as well as attenuated cell proliferation and tumor growth.
Paul A M Michels - One of the best experts on this subject based on the ideXlab platform.
-
compartmentation of Phosphoglycerate kinase in trypanosoma brucei plays a critical role in parasite energy metabolism
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Judith Blattner, Sandra Helfert, Paul A M Michels, Christine ClaytonAbstract:African trypanosomes compartmentalize glycolysis in a microbody, the glycosome. When growing in the mammalian bloodstream, trypanosomes contain only a rudimentary mitochondrion, and the first seven glycolytic enzymes, including Phosphoglycerate kinase, are located in the glycosome. Procyclic trypanosomes, growing in the gut of tsetse flies, possess a fully developed mitochondrion that is active in oxidative phosphorylation. The first six glycolytic enzymes are still glycosomal, but Phosphoglycerate kinase is now found in the cytosol. We demonstrate here that bloodstream trypanosomes are killed by expression of cytosolic Phosphoglycerate kinase. The toxicity depends on both enzyme activity and cytosolic location. One possible explanation is that cytosolic Phosphoglycerate kinase creates an ATP-generating shunt in the cytosol, thus preventing full ATP regeneration in the glycosome and ultimately inhibiting the first, ATP-consuming, steps of glycolysis.
-
synergistic effects of substrate induced conformational changes in Phosphoglycerate kinase activation
Nature, 1997Co-Authors: Bradley E Bernstein, Paul A M MichelsAbstract:Phosphoglycerate kinase (PGK), a key enzyme in glycolysis, catalyses the transfer of a phosphoryl-group from 1,3-bis-Phosphoglycerate to ADP to form 3-Phosphoglycerate and ATP. Despite extensive kinetic and structural investigations over more than two decades, the conformation assumed by this enzyme during catalysis remained unknown. Here we present the 2.8 Angstrom crystal structure of a ternary complex of PGK from Trypanosoma brucei, the causative agent of sleeping sickness. This structure determination relied on a procedure in which fragments containing less than 10% of the scattering mass were successively positioned in the unit cell to obtain phases. The PGK ternary complex exhibits a dramatic dosing of the large cleft between the two domains seen in all previous studies(1-6), thereby bringing the two ligands, 3-Phosphoglycerate and ADP into dose proximity. Our results demonstrate that PGK is a hinge-bending enzyme, reveal a novel mechanism in which substrate-induced effects combine synergistically to induce major conformational changes and, to our knowledge, afford the first observation of the PGK active site in a catalytic conformation.
