Metabolism of the acutely ischemic dog heart. II. Interpretation of a model

1979 ◽  
Vol 236 (1) ◽  
pp. R31-R39
Author(s):  
D. Garfinkel ◽  
M. J. Achs
Keyword(s):  
Computer Model ◽  
Glycolytic Enzymes ◽  
Glycolytic Pathway ◽  
Muscle Proteins ◽  
Dog Heart ◽  
Phosphohexose Isomerase ◽  
Glycolytic Oscillations ◽  
Pathway Flux ◽  
Reducing Equivalents

The glycolytic oscillations occurring in an acutely ischemic dog heart are analyzed with a computer model. The major regulations of the glycolytic pathway flux occur at phosphohexose isomerase, which is inhibited by accumulated pentose shunt intermediates; at phosphorylase, which shapes the first cycle of the oscillation; and at aldolase, which shapes the last two cycles. Aldolase is not under normal substrate control. Its activity, and that of some subsequent glycolytic enzymes, appears to be regulated by known interactions with the muscle proteins. The mitochondria become reduced as a result of anoxia, and their metabolism reorganizes to export rather than import reducing equivalents. It is in general feasible to account for the behavior of this preparation in terms of the known metabolism of less severely perturbed hearts, especially (but not completely) in terms of effects of anoxia. The reasons for the inapplicability of the crossover theorem previously used to analyze this preparation are described.

Metabolism of totally ischemic excised dog heart I. Construction of a computer model

1979 ◽  
Vol 237 (5) ◽  
pp. R318-R326 ◽  
Author(s):  
Murray J. Achs ◽  
David Garfinkel
Keyword(s):  
Computer Model ◽  
Metabolic Regulation ◽  
Krebs Cycle ◽  
The Body ◽  
Heavy Sedation ◽  
Dog Heart ◽  
Rat Hearts ◽  
Heart Preparation ◽  
Time Courses ◽  
Underlying Mechanisms

Construction and fit to the experimental data of a computer model of glycolysis, the Krebs cycle, and related metabolism in an ischemic dog heart preparation, involving 122 metabolites, 65 enzymes, and 406 chemical reactions, is described. The experimental preparation simulated is a dog heart excised from the body, placed in a beaker of Tyrode's solution, and sampled for 100 min; the model required only moderate modification from models representing perfused rat hearts, and little modification from a model of another ischemic dog heart preparation. Common underlying mechanisms for the ischemia are indicated, although this preparation appears to evolve more slowly with time, perhaps owing to heavy sedation and diffusion-limited transport. Lactate is, at first, exported and then accumulates intracellularly; pH falls, but not as much in the mitochondria as the cytoplasm; redox couples go reduced, but with counterintuitive time courses; calcium phosphate is calculated to precipitate, as often observed in cardiac ischemia enzymes; glycolysis; simulation; metabolic regulation Submitted on October 24, 1978 Accepted on May 21, 1979

CARBOHYDRATE METABOLISM IN THE TWO-SPOTTED SPIDER MITE, TETRANYCHUS TELARIUS L.: II. EMBDEN–MEYERHOF PATHWAY

1963 ◽  
Vol 41 (7) ◽  
pp. 1595-1602 ◽  
Author(s):  
K. N. Mehrotra
Keyword(s):  
Carbohydrate Metabolism ◽  
Spider Mite ◽  
Lactic Dehydrogenase ◽  
Glycolytic Enzymes ◽  
Glycolytic Pathway ◽  
Glycerophosphate Dehydrogenase ◽  
End Products ◽  
Two Spotted Spider Mite

Evidence demonstrating the occurrence of some of the glycolytic enzymes in the two-spotted spider mite, Tetranychus telarius L., has been obtained. The glycolytic pathway in mites appears to be similar to the Embden–Meyerhof type described for other organisms.The enzymes shown to be present in the mite are: phosphohexoisomerase, phosphofructokinase, aldolase, α-glycerophosphate dehydrogenase, and glyceraldehyde-3-phosphate dehydrogenase. The hexokinase and lactic dehydrogenase, if present, are in very low titre. The end products of glycolysis in the mites were shown to be α-glycerophosphate and pyruvate.

scholarly journals Anti-malarial drugs as potential inhibitors of leishmania glycolytic enzymes: Development of new anti-leishmanial agents

2020 ◽  
Vol 5 (3) ◽  
pp. 77
Author(s):  
Bashir Alsiddig Yousef ◽  
Tanzeel Haider Elwaseela ◽  
Tagwa Abdalla Ali ◽  
Fatima Elamin Mohammed ◽  
Wala Osman Mohammed ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Leishmania Donovani ◽  
Triosephosphate Isomerase ◽  
Antimalarial Drugs ◽  
Binding Energies ◽  
Glycolytic Enzymes ◽  
Glycolytic Pathway ◽  
Glycerol 3 Phosphate Dehydrogenase ◽  
Antileishmanial Activities

Leishmaniasis is one of the most important endemic diseases in Sudan. The glycolytic pathway is one of the essential pathways in the survival and pathogenicity of the leishmania parasite. This study aimed to evaluate the antileishmanial activities of three antimalarial drugs through targeting the glycolytic pathway inside the parasite. Antileishmanial activities of artesunate, quinine and mefloquine were evaluated using an in vitro anti-promastigote assay. Then, in silico molecular docking was conducted using Autodock 4.0 software to study the molecular interactions of antimalarial drugs to different key glycolytic enzymes. The results of the current study, Artesunate, quinine, and mefloquine showed effective inhibitory activities against L. donovani with IC50 values of 58.85, 40.24, and 20.06 μg/ml, respectively. Molecular docking analysis revealed interesting interactions between different antimalarial drugs and various glycolytic enzymes (Glucose-6-phosphate isomerase, Triosephosphate isomerase, Glycerol-3-phosphate dehydrogenase, Glyceraldehyde-3-phosphate dehydrogenase and Pyruvate kinase). Moreover, these drugs interact with different amino acid residues of the proteins with satisfactory binding energies, particularly with artesunate. According to binding energies, Glycerol-3-phosphate dehydrogenase was represented the most potential target for three tested drugs. Collectively, our results showed promising antileishmanial activities of different antimalarial that may mediated through inhibition of glycolysis process in leishmania donovani promastigote.

scholarly journals Expression of glycolytic enzymes in ovarian cancers and evaluation of the glycolytic pathway as a strategy for ovarian cancer treatment

BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Chrysi Xintaropoulou ◽  
Carol Ward ◽  
Alan Wise ◽  
Suzanna Queckborner ◽  
Arran Turnbull ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Treatment ◽  
Glycolytic Enzymes ◽  
Glycolytic Pathway ◽  
Ovarian Cancers

CARBOHYDRATE METABOLISM IN THE TWO-SPOTTED SPIDER MITE, TETRANYCHUS TELARIUS L.: II. EMBDEN–MEYERHOF PATHWAY

1963 ◽  
Vol 41 (1) ◽  
pp. 1595-1602
Author(s):  
K. N. Mehrotra
Keyword(s):  
Carbohydrate Metabolism ◽  
Spider Mite ◽  
Lactic Dehydrogenase ◽  
Glycolytic Enzymes ◽  
Glycolytic Pathway ◽  
Glycerophosphate Dehydrogenase ◽  
End Products ◽  
Two Spotted Spider Mite

Evidence demonstrating the occurrence of some of the glycolytic enzymes in the two-spotted spider mite, Tetranychus telarius L., has been obtained. The glycolytic pathway in mites appears to be similar to the Embden–Meyerhof type described for other organisms.The enzymes shown to be present in the mite are: phosphohexoisomerase, phosphofructokinase, aldolase, α-glycerophosphate dehydrogenase, and glyceraldehyde-3-phosphate dehydrogenase. The hexokinase and lactic dehydrogenase, if present, are in very low titre. The end products of glycolysis in the mites were shown to be α-glycerophosphate and pyruvate.

scholarly journals Reconstructing the Mosaic Glycolytic Pathway of the Anaerobic Eukaryote Monocercomonoides

2006 ◽  
Vol 5 (12) ◽  
pp. 2138-2146 ◽  
Author(s):  
Natalia A. Liapounova ◽  
Vladimir Hampl ◽  
Paul M. K. Gordon ◽  
Christoph W. Sensen ◽  
Lashitew Gedamu ◽  
...  
Keyword(s):  
Tricarboxylic Acid Cycle ◽  
Glycolytic Enzymes ◽  
Glycolytic Pathway ◽  
Phosphoglycerate Mutase ◽  
Fructose Bisphosphate ◽  
Pyruvate Orthophosphate Dikinase ◽  
Orthophosphate Dikinase ◽  
Fructose Bisphosphate Aldolase ◽  
Efficient Alternative ◽  
Eukaryotic Supergroup

ABSTRACT All eukaryotes carry out glycolysis, interestingly, not all using the same enzymes. Anaerobic eukaryotes face the challenge of fewer molecules of ATP extracted per molecule of glucose due to their lack of a complete tricarboxylic acid cycle. This may have pressured anaerobic eukaryotes to acquire the more ATP-efficient alternative glycolytic enzymes, such as pyrophosphate-fructose 6-phosphate phosphotransferase and pyruvate orthophosphate dikinase, through lateral gene transfers from bacteria and other eukaryotes. Most studies of these enzymes in eukaryotes involve pathogenic anaerobes; Monocercomonoides, an oxymonad belonging to the eukaryotic supergroup Excavata, is a nonpathogenic anaerobe representing an evolutionarily and ecologically distinct sampling of an anaerobic glycolytic pathway. We sequenced cDNA encoding glycolytic enzymes from a previously established cDNA library of Monocercomonoides and analyzed the relationships of these enzymes to those from other organisms spanning the major groups of Eukaryota, Bacteria, and Archaea. We established that, firstly, Monocercomonoides possesses alternative versions of glycolytic enzymes: fructose-6-phosphate phosphotransferase, both pyruvate kinase and pyruvate orthophosphate dikinase, cofactor-independent phosphoglycerate mutase, and fructose-bisphosphate aldolase (class II, type B). Secondly, we found evidence for the monophyly of oxymonads, kinetoplastids, diplomonads, and parabasalids, the major representatives of the Excavata. We also found several prokaryote-to-eukaryote as well as eukaryote-to-eukaryote lateral gene transfers involving glycolytic enzymes from anaerobic eukaryotes, further suggesting that lateral gene transfer was an important factor in the evolution of this pathway for denizens of this environment.

scholarly journals Core Fermentation (CoFe) granules focus coordinated glycolytic mRNA localization and translation to fuel glucose fermentation

2019 ◽  
Author(s):  
Fabian Morales-Polanco ◽  
Christian Bates ◽  
Jennifer Lui ◽  
Joseph Casson ◽  
Clara A. Solari ◽  
...  
Keyword(s):  
Metabolic Pathway ◽  
Mrna Localization ◽  
Enzyme Synthesis ◽  
Human Cells ◽  
Live Cell ◽  
Glycolytic Enzymes ◽  
Glycolytic Pathway ◽  
Glucose Fermentation ◽  
High Level ◽  
And Control

SummaryGlycolysis is a fundamental metabolic pathway for glucose catabolism across biology, and glycolytic enzymes are amongst the most abundant proteins in cells. Their expression at such levels provides a particular challenge. Here we demonstrate that the glycolytic mRNAs are localized to granules in yeast and human cells. Detailed live cell and smFISH studies in yeast show that the mRNAs are actively translated in granules, and this translation appears critical for the localization. Furthermore, this arrangement is likely to facilitate the higher level organisation and control of the glycolytic pathway. Indeed, the degree of fermentation required by cells is intrinsically connected to the extent of mRNA localization to granules. On this basis, we term these granules, Core Fermentation (CoFe) granules; they appear to represent translation factories allowing high-level co-ordinated enzyme synthesis for a critical metabolic pathway.

Metabolism of the acutely ischemic dog heart. I. Construction of a computer model

1979 ◽  
Vol 236 (1) ◽  
pp. R21-R30
Author(s):  
M. J. Achs ◽  
D. Garfinkel
Keyword(s):  
Computer Model ◽  
Experimental Error ◽  
Krebs Cycle ◽  
Pyridine Nucleotides ◽  
Dog Heart ◽  
Glycolytic Intermediates ◽  
Metabolic Difference ◽  
Principal Change ◽  
Underlying Mechanisms ◽  
Large Animals

Construction of a computer model of glycolysis, the Krebs cycle, and related metabolism in acutely ischemic dog heart, involving 122 metabolites, 65 enzymes, and 406 chemical reactions, is described. A previous model of the same metabolism in normal-flow rat heart was modified to fit ischemic dog heart experimental data to within experimental error. The result resembles other models of ischemic heart preparations, implying common underlying mechanisms. The principal change made was reduction of enzyme amounts, consistent with the generally slower metabolism of large animals, suggesting that differing enzyme amounts are a major component of interspecies metabolic difference. Glycolytic intermediates oscillate, asynchronously and with large changes in level; pyridine nucleotides become highly reduced; pH falls, but mitochondria stay alkaline relative to cytoplasm even after oxidative phosphorylation stops.

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