scholarly journals Maximum activities of key enzymes of glycolysis, glutaminolysis, pentose phosphate pathway and tricarboxylic acid cycle in normal, neoplastic and suppressed cells

1990 ◽  
Vol 265 (2) ◽  
pp. 503-509 ◽  
Author(s):  
M Board ◽  
S Humm ◽  
E A Newsholme
Keyword(s):  
Pyruvate Kinase ◽  
Pentose Phosphate Pathway ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Pentose Phosphate ◽  
Neoplastic Cells ◽  
Acid Cycle ◽  
Key Enzymes ◽  
Metastatic Cells ◽  
Tumorigenic Cells

1. Maximal activities of some key enzymes of glycolysis, the pentose phosphate pathway, the tricarboxylic acid cycle and glutaminolysis were measured in homogenates from a variety of normal, neoplastic and suppressed cells. 2. The relative activities of hexokinase and 6-phosphofructokinase suggest that, particularly in neoplastic cells, in which the capacity for glucose transport is high, hexokinase could approach saturation in respect to intracellular glucose; consequently, hexokinase and phosphofructokinase could play an important role in the regulation of glycolytic flux in these cells. 3. The activity of pyruvate kinase is considerably higher in tumorigenic cells than in non-tumorigenic cells and higher in metastatic cells than in tumorigenic cells: for non-tumorigenic cells the activities range from 28.4 to 574, for tumorigenic cells from 899 to 1280, and for metastatic cells from 1590 to 1627 nmol/min per mg of protein. 4. The ratio of pyruvate kinase activity to 2 x phosphofructokinase activity is very high in neoplastic cells. The mean is 22.4 for neoplastic cells, whereas for muscle from 60 different animals it is only 3.8. 5. Both citrate synthase and isocitrate dehydrogenase activities are present in non-neoplastic and neoplastic cells, suggesting that the full complement of tricarboxylic-acid-cycle enzymes are present in these latter cells. 6. In neoplastic cells, the activity of glutaminase is similar to or greater than that of hexokinase, which suggests that glutamine may be as important as glucose for energy generation in these cells.

Carbohydrate metabolism in Acanthamoeba castellanii. 1. The activity of key enzymes and [14C]-glucose metabolism

1973 ◽  
Vol 19 (9) ◽  
pp. 1131-1136 ◽  
Author(s):  
Lansing M. Prescott ◽  
Harold E. Hoyme ◽  
Darlene Crockett ◽  
Elena Hui
Keyword(s):  
Carbohydrate Metabolism ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Fumarate Hydratase ◽  
Acanthamoeba Castellanii ◽  
Tricarboxylic Acid ◽  
Pentose Phosphate ◽  
Acid Cycle ◽  
Key Enzymes ◽  
Glyceraldehydephosphate Dehydrogenase

The specific activities of a number of the key enzymes involved in carbohydrate metabolism in Acanthamoeba castellanii (Neff clone I–12) have been determined. The following Embden–Meyerhof and pentose phosphate pathway enzymes were present: glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, hexokinase, phosphofructokinase, hexose diphosphatase, aldolase, glyceraldehydephosphate dehydrogenase, pyruvate kinase, and pyruvate-phosphate dikinase. The following tricarboxylic acid cycle enzymes were also found: citrate synthase, aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase, and malate dehydrogenase. The degradation of glucose-U-14C to 14CO2 was examined. Aerobic 14CO2 production from glucose-U-14C was 3.4-fold greater than anaerobic production. The data provide further evidence that the Embden–Meyerhof, pentose phosphate, and tricarboxylic acid cycle pathways are probably functional in A. castellanii.

Upregulation of Pentose Phosphate Pathway and Preservation of Tricarboxylic Acid Cycle Flux after Experimental Brain Injury

2005 ◽  
Vol 22 (10) ◽  
pp. 1052-1065 ◽  
Author(s):  
Brenda L. Bartnik ◽  
Richard L. Sutton ◽  
Masamichi Fukushima ◽  
Neil G. Harris ◽  
David A. Hovda ◽  
...  
Keyword(s):  
Brain Injury ◽  
Pentose Phosphate Pathway ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Pentose Phosphate ◽  
Acid Cycle

Ontogeny of pyruvate dehydrogenase complex and key enzymes involved in glycolysis and tricarboxylic acid cycle in rabbit fetal lung, heart, and liver

1990 ◽  
Vol 68 (10) ◽  
pp. 1210-1217 ◽  
Author(s):  
Bhagu R. Bhavnani ◽  
Duncan G. Wallace
Keyword(s):  
Pyruvate Kinase ◽  
Pyruvate Dehydrogenase ◽  
Fetal Liver ◽  
Tricarboxylic Acid Cycle ◽  
Pyruvate Dehydrogenase Complex ◽  
Fetal Lung ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Key Enzymes ◽  
Dehydrogenase Complex

The metabolic pathways by which the glycogen is utilized by fetal tissues is not well established. In the present study the ontogeny of seven key enzymes involved in glycolysis and the tricarboxylic acid cycle has been established for rabbit fetal lung, heart, and liver. In the fetal lung the activities of phosphofructokinase, pyruvate kinase, lactic dehydrogenase, citrate synthase, and malate dehydrogenase increase from day 21 to 25. Thereafter the levels either drop to day 19 levels or do not change. The isocitrate dehydrogenase activity continues to increase from day 19 of gestation to maximum level on day 31 of gestation. In fetal heart the pattern of activity is similar, but in fetal liver most of the enzymes reach maximum levels earlier and, with the exception of pyruvate kinase, do not show a significant fall in activity near term. The pattern of development of pyruvate dehydrogenase complex is different; maximum activity is observed on day 27 in fetal lung and heart and on day 21 in fetal liver. These results indicate that all three fetal tissues can oxidize glucose. Also, the accumulation of glycogen, particularly in fetal lung, appears to ensure that at specific times during gestation adequate quantities of energy (ATP) and substrates, required for surfactant phospholipid synthesis, are available independent of maternal supply of glucose or during brief episodes of hypoxia.Key words: glycogen, glycolysis, tricarboxylic acid cycle, pyruvate dehydrogenase, surfactant.

scholarly journals Biochemical adaptation in rat liver in response to marginal oxygen toxicity

1971 ◽  
Vol 125 (2) ◽  
pp. 439-447 ◽  
Author(s):  
R. R. Gorman ◽  
J. P. Jordan ◽  
J. B. Simmons ◽  
D. P. Clarkson
Keyword(s):  
Sea Level ◽  
Pentose Phosphate Pathway ◽  
Tricarboxylic Acid Cycle ◽  
Oxygen Toxicity ◽  
Liver Glycogen ◽  
Tricarboxylic Acid ◽  
Pentose Phosphate ◽  
Acid Cycle ◽  
Biochemical Adaptation ◽  
Glucose 6 Phosphate Dehydrogenase

1. Hepatic glucose 6-phosphate dehydrogenase activity was increased in rats exposed to 5lb/in2 (equivalent to 27000ft), 100% O2 when compared with control animals in a 14.7lb/in2 (sea level), air environment. Glyceraldehyde 3-phosphate dehydrogenase, isocitrate dehydrogenase, and succinate dehydrogenase were not affected by the 5lb/in2, 100% O2 environment. 2. Animals exposed to the hyperoxic environment consumed food, expired CO2 and gained weight at the same rate as normoxic control animals. Additionally, blood glucose and liver glycogen concentrations were unchanged in the hyperoxic animals. The only readily apparent physiological difference in the hyperoxic animals was a decreased haematocrit. 3. The increase in glucose 6-phosphate dehydrogenase was eliminated by the injection of actinomycin D or cycloheximide. 4. Expiration of 14CO2 from [1-14C]glucose was approximately the same in hyperoxic and normoxic rats. However, 14CO2 expiration from [6-14C]glucose was markedly decreased in the animals exposed to the hyperoxic environment. 5. Calculations of the relative importance of the pentose phosphate pathway versus the tricarboxylic acid cycle plus glycolysis indicated that the livers from animals in the 5lb/in2, 100% O2 environment metabolized twice as much carbohydrate by way of the pentose phosphate pathway as did those from the sea-level air control animals. 6. In livers of rats exposed to 5lb/in2, 100% O2 the concentrations of pyruvate, citrate and 2-oxoglutarate were increased, that of isocitrate was slightly elevated, whereas the concentrations of succinate, fumarate and malate were decreased. 7. An inactivation of both tricarboxylic acid cycle lipoate-containing dehydrogenases, pyruvate and 2-oxoglutarate, under hyperoxic conditions is proposed. 8. The adaptive significance of the induction of glucose 6-phosphate dehydrogenase and the resultant production of NADPH under hyperoxic conditions is discussed.

scholarly journals Dual metabolomic profiling uncovers Toxoplasma manipulation of the host metabolome and the discovery of a novel parasite metabolic capability

2018 ◽  
Author(s):  
William J. Olson ◽  
David Stevenson ◽  
Daniel Amador-Noguez ◽  
Laura J. Knoll
Keyword(s):  
Pentose Phosphate Pathway ◽  
Time Course ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Pentose Phosphate ◽  
Acid Cycle ◽  
Obligate Intracellular ◽  
Host Parasite ◽  
Host Metabolism ◽  
Sedoheptulose Bisphosphatase

AbstractThe obligate intracellular parasite Toxoplasma gondii is auxotrophic for several key metabolites and must scavenge these from the host. It is unclear how Toxoplasma manipulates host metabolism for its overall growth rate and non-essential metabolites. To address this question, we measured changes in the joint host-parasite metabolome over a time course of infection. Host and parasite transcriptomes were simultaneously generated to determine potential changes in metabolic enzyme levels. Toxoplasma infection increased activity in multiple metabolic pathways, including the tricarboxylic acid cycle, the pentose phosphate pathway, glycolysis, amino acid synthesis, and nucleotide metabolism. Our analysis indicated that changes in some pathways, such as the tricarboxylic acid cycle, derive from the parasite, while changes in others, like the pentose phosphate pathway, were host and parasite driven. Further experiments led to the discovery of a Toxoplasma enzyme, sedoheptulose bisphosphatase, which funnels carbon from glycolysis into ribose synthesis through a energetically driven dephosphorylation reaction. This second route for ribose synthesis resolves a conflict between the Toxoplasma tricarboxylic acid cycle and pentose phosphate pathway, which are both NADP+ dependent. During periods of high energetic and ribose need, the competition for NADP+ could result in lethal redox imbalances. Sedoheptulose bisphosphatase represents a novel step in Toxoplasma central carbon metabolism that allows Toxoplasma to satisfy its ribose demand without using NADP+. Sedoheptulose bisphosphatase is not present in humans, highlighting its potential as a drug target.Author SummaryThe obligate intracellular parasite Toxoplasma is commonly found among human populations worldwide and poses severe health risks to fetuses and individuals with AIDS. While some treatments are available they are limited in scope. A possible target for new therapies is Toxoplasma’s limited metabolism, which makes it heavily reliant in its host. In this study, we generated a joint host/parasite metabolome to better understand host manipulation by the parasite and to discover unique aspects of Toxoplasma metabolism that could serve as the next generation of drug targets. Metabolomic analysis of Toxoplasma during an infection time course found broad activation of host metabolism by the parasite in both energetic and biosynthetic pathways. We discovered a new Toxoplasma enzyme, sedoheptulose bisphosphatase, which redirects carbon from glycolysis into ribose synthesis. Humans lack sedoheptulose bisphosphatase, making it a potential drug target. The wholesale remodeling of host metabolism for optimal parasite growth is also of interest, although the mechanisms behind this host manipulation must be further studied before therapeutic targets can be identified.

Biosynthesis of ε-rhodomycinone from glucose by Streptomyces C5 and comparison with intermediary metabolism of other polyketide-producing streptomycetes

1988 ◽  
Vol 34 (11) ◽  
pp. 1235-1240 ◽  
Author(s):  
Michael L. Dekleva ◽  
William R. Strohl
Keyword(s):  
Pentose Phosphate Pathway ◽  
Enzyme Activities ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Pentose Phosphate ◽  
Anthracycline Antibiotics ◽  
Glyoxylate Bypass ◽  
Acid Cycle ◽  
Minor Contribution ◽  
A Minor

The catabolism of glucose by Streptomyces C5, a producer of anthracycline antibiotics, was investigated to determine the pathways that supply precursors for anthracycline biosynthesis. Carbons for the biosynthesis of ε-rhodomycinone, an anthracycline aglycone, from radiolabelled glucose were derived primarily from the Embden–Meyerhof–Parnas pathway, with a minor contribution from the pentose phosphate pathway. Furthermore, the anthracycline-producing strain, Streptomyces C5, as well as Streptomyces aureofaciens and Streptomyces lividans, strains that produce nonanthracycline polyketide antibiotics, displayed enzyme activities indicative of the Embden–Meyerhof–Parnas and pentose phosphate glycolytic pathways. As determined from labelling patterns, Streptomyces C5 apparently has a complete tricarboxylic acid cycle, but does not have a glyoxylate bypass pathway.

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