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[Quantitative model of human erythrocyte glycolysis. II. Effect of arsenate on glycolysis. Experimental study of the relationship between the rate of glycolysis and the ATP concentration].

The effect of arsenate on human erythrocyte glycolysis was studied. The stationary rate of glucose consumption rises and then drops with a gradual increase of arsenate concentration while ATP and glucose-6-phosphate concentrations drop monotonically. A plot of glucose consumption rate against ATP concentration gives a bell-like curve. This curve is the same for different donors if it is plotted in relative units with values at zero arsenate concentration taking for 100%, while the absolute values obtained for separate donors are very different. The normal (physiological) point is situated on the steeply descending part of the curve.

Adenosine Triphosphate↗

AMP deaminase as a control system of glycolysis in yeast. Mechanism of the inhibition of glycolysis by fatty acid and citrate.

The role of fatty acid and citrate on the interaction of the AMP deaminase (EC 3.5.4.6) reaction with glycolysis was investigated using permeabilized yeast cells. (a) Linolenate and citrate inhibited glycolytic flux and the recovery of the adenylate energy charge; however, linolenate remarkably retarded the depletion of the total adenylate pool, which was not at all affected by the addition of citrate. (b) Linolenate inhibited AMP deaminase activity in situ, resulting in the subsequent decrease in ammonium production, which reduced the activity of 6-phosphofructokinase (EC 2.7.1.11), whereas linolenate itself had no ability to inhibit the phosphofructokinase activity in the presence of excess ammonium concentration. (c) Citrate inhibited the activity of phosphofructokinase in situ in the presence and absence of ammonium ion, followed by an inhibition of glycolysis; however, AMP deaminase activity was not inhibited by citrate. The inhibition of glycolysis by fatty acids can be accounted for by the lowered activity of phosphofructokinase as a result of the decreased level of ammonium ion through the inhibition of the AMP deaminase reaction by these ligands, whereas the effect of citrate on glycolysis is a direct inhibition of phosphofructokinase without affecting the activity of AMP deaminase. Fatty acid and citrate, a principal metabolic product of fatty acid oxidation, can be responsible for the control of glycolysis in two different manners.

AMP Deaminase↗

Glycolysis of red cells suspended in solutions of impermeable solutes. Intracellular pH and glycolysis.

The glycolytic rate human red cells suspended in a sucrose medium of low or physiological pH was higher than that of the cells suspended in Ringer's medium of the same. pH. The medium pHP-glycolytic rate curve of red cells suspended in soucrose media shifted to the acidic side by about one unit compared with that of cells suspended in Ringer's medium. Similarly, the pattern of glycolytic intermediates in red cells suspended in a sucrose medium resembled that in cells suspended in Ringer's solution of about one unit higher pH. These phenomena could be ascribed to the change of intracellular pH, which was measured by the 5,5'-dimethyl-oxazolidine-2,4-dione method. A similar stimulation of glycolysis was observed when sodium citrate was added to red cells suspended in Ringer's solution at constant pH. These observations indicate that membrane-impermeable non-electrolytes or anions stimulate glycolysis of red cells by elevation ofthe intracellular pH. Red cell glycolysis is influenced mainly by the intracellular pH rather than by the pH of the suspending medium.

Adenosine Triphosphate↗

[Experimental study on the mechanisms of enhancement of aerobic glycolysis of muscles in burns and sepsis--the verification of the existence and the enhancement of the aerobic glycolysis of muscles in early postburn period and sepsis].

OBJECTIVE: To verify if aerobic glycolysis exists in the muscle cells in normal rats and to analyze the changes in aerobic glycolysis in the muscle cells in the early postburn period and in septic states. METHOD: Using septic model of rats, we established the in vitro muscle incubation system with sufficient oxygen supply as well as the NADH fluoremetric method for the detection of trace amount of lactate in the samples. Extensor digitorium longus (EDL) and soleus muscles which represent two types of muscle fiber were studied. RESULTS: In the early postburn period as well as in septic states, the lactate production of muscle cells was significantly elevated as compared to the normal controls even though the muscles were incubated in a fully oxygenated media. The levels of aerobic glyoclysis, as well as its changes in postburn period and in septic states, vary depending on the difference in the fiber composition of the muscles. CONCLUSION: Muscle cells might develop a kind of metabolic enhancement which is referred to as aerobic glycolysis rather than the metabolic defect which results from tissue hypoperfusion and hypoxia in the early postburn period as well as in septic states. This provides us a special insight to elucidate the mechanisms of the metabolic derangement in the early postburn period and in sepsis.

Animals↗

Glycolysis and brain function: [K+]o stimulation of protein synthesis and K+ uptake require glycolysis.

Glucose is essentially the sole energy substrate in the normally functioning brain. There are, however, situations in which other substrates can partially substitute for glucose and maintain an apparently normal brain function. However, in no case has it been possible to completely substitute other substrates for glucose and maintain normal brain function. Studies on insulin-induced hypoglycemia suggest that this glucose dependence does not result from its involvement in ATP generation. Two explantation that have been offered are that toxic catabolites arise if nonglucose substrates are oxidized or that glycolysis is necessary to maintain neurotransmitter metabolism. We consider a third basis for the glucose requirement: our past studies have shown that hippocampal slice protein synthesis is activated by small increases in extracellular [K+] ([K+]o), and that this results from activation of K+ uptake into brain cells. We find that this process specifically requires aerobic glycolysis. The basis for the requirement appears to be that [K+]o activation of the Na+-K+ pump is specifically dependent on glycolytically generated energy. Thus, it is possible that glucose is required to maintain normal K+ clearance from the extracellular space during neural activity. This could partially account for the dependence of brain function on glycolysis.

Adenosine Triphosphate↗

Tumor Treatment Response Based on Visual and Quantitative Changes in Global Tumor Glycolysis Using PET-FDG Imaging. The Visual Response Score and the Change in Total Lesion Glycolysis.

"Functional" tumor treatment response parameters have been developed to measure treatment induced biochemical changes in the entire tumor mass, using positron emission tomography (PET) and [F-18] fludeoxyglucose (FDG). These new parameters are intended to measure global changes in tumor glycolysis. The response parameters are determined by comparing the pre- and posttreatment PET-FDG images either visually from the change in image appearance in the region of the tumor, or quantitatively based on features of the calibrated digital PET image. The visually assessed parameters are expressed as a visual response score (VRS), or visual response index (VRI), as the estimated percent response of the tumor. Visual Response Score (VRS) is recorded on a 5 point response scale (0-4): 0: no response or progression; 1: 1-33%; 2: >33%-66%; 3: >66%-99%; and 4: >99%, estimated response, respectively. The quantitative changes are expressed as total lesion glycolysis TLG or as the change in TLG during treatment, also called deltaTLG or Larson-Ginsberg Index (LGI), expressed as percent response. The volume of the lesion is determined from the PET-FDG images by an adaptive thresholding technique. This response index is computed as, deltaTLG (LGI) = {[(SUV(ave))(1) * (Vol)(1) - (SUV(ave))(2) * (Vol)(2)]/[(SUV(ave))(1) * (Vol)(1)]} * 100. Where "1" and "2" denote the pre- and posttreatment PET-FDG, scans respectively. Pre- and posttreatment PET-FDG scans were performed on a group of 41 locally advanced lung (2), rectal (17), esophageal (16) and gastric (6) cancers. These patients were treated before surgery with neoadjuvant chemo-radiation. Four experienced PET readers determined individual VRS and VRI blinded to each other as well as to the clinical history. Consensus VRS was obtained based on a discussion. The interobserver variability captured by intraclass correlation coefficient was 89.7%. In addition, reader reliability was assessed for the categorized VRS using Kendall's coefficient of concordance for ordinal data and was found to be equal to 85% This provided assurance that these response parameters were highly reproducible. The correlation of deltaTLG with % change in SUV(ave) and % change in SUV(max), as widely used parameters of response, were 0.73 and 0.78 (P <.0001) respectively. The corresponding correlation of VRI were 0.63 and 0.64 (P <.0001) respectively. Both deltaTLG and VRI showed greater mean changes than SUV maximum or average (59.7% and 76% vs. 46.9% and 46.8%). We conclude that VRS and deltaTLG are substantially correlated with other response parameters and are highly reproducible. As global measures of metabolic response, VRS, VRI and deltaTLG (LGI) should provide complementary information to more commonly used PET response parameters like the metabolic rate of FDG (MRFDG), or the standardized uptake value (SUV), that are calculated as normalized per gram of tumor. These findings set the stage for validation studies of the VRS and deltaTLG as objective measures of clinical treatment response, through comparison to the appropriate gold standards of posttreatment histopathology, recurrence free survival, and disease specific survival in well characterized populations of patients with locally advanced cancers.

Journal Article↗

Studies on human platelet glycolysis. Effect of glucose, cyanide, insulin, citrate, and agglutination and contraction on platelet glycolysis.

Evidence for a metabolically active plasma-free platelet system is presented. Glycogenolysis was found to be a potent pathway for lactate production. Aerobic glycolysis constituted a major fraction of glucose metabolized. Both insulin and cyanide increased lactate production in the presence of glucose. The Krebs cycle appeared to be operative for ATP synthesis when citrate was used as substrate. The first stages of gluconeogenesis were noted to be present. Glucose uptake contributed to increased lactate production.Thrombin, epinephrine, and ADP resulted in platelet agglutination and contraction and increased platelet glycogenolysis (phosphorylase activity). Epinephrine appeared to be a more potent activator of phosphorylase, resulting in a 70% increase in glucose 6-phosphate levels. Thrombin and epinephrine both increased glucose uptake and lactate production. Glucose uptake decreased in the presence of ADP. Except for incubations with epinephrine, glucose 6-phosphate remained constant under conditions in which lactate flux increased 3-fold and glucose uptake increased 2-fold. Thrombin, epinephrine, and ADP decreased ATP levels in the presence or absence of glucose.

Adenine Nucleotides↗

[Glycolysis in the eye tissues of the rabbit in ontogeny. I. The enzymes of glycolysis and hexosemonophosphate shunt].

The activity of the enzymes of glycolysis (phosphofructokinase, aldolase, pyruvate kinase, lactate dehydrogenase) and hexose monophosphate shunt (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase) was determined in the eye tissues of the rabbit at different stages of ontogenesis. The activity of these enzymes in the retina was shown to be higher than in other eye tissues. In the uveal tract (iris, ciliary bodies, uvea) the activity of glycolytic enzymes changes with the age. The greatest changes in the activity of enzymes were found during the period of the opening of eyelids. The activity of the enzymes of hexose monophosphate shunt in the eye tissues increases with the age. The relative activity of dehydrogenases of the hexose monophosphate shunt after the establishment of visual function is, however, not high and does not exceed that of phosphofructokinase and pyruvate kinase in the eye tissues of the rabbit.

Age Factors↗

[Glycolysis in the eye tissues of the rabbit in ontogeny. II. The dynamics of the changes in the level of glycolysis and lactic acid intermediates].

The level of intermediates of glycolysis (hexose monophosphates, fructose-1,6-diphosphate, pyruvate) and the rate of lactic acid synthesis (under the aerobic conditions without substrates and in the presence of glucose, glucose-6-phosphate and fructose-1,6-diphosphate) were measured in the eye tissues (retina, iris, ciliary bodies, uvea) of rabbits of different age. The rate of lactic acid synthesis under the aerobic conditions in the retina and uveal tract increases of the latter the rate of lactic acid synthesis was the highest. The greatest increase in the lactic acid content was observed during the first 15 days of postnatal development.

Aerobiosis↗

Post-mortem glycolysis in skeletal muscle. The extent of glycolysis in diluted preparation of mammalian muscle.

1. Sheep-, rabbit- and ox-muscle minces prepared soon after slaughter were diluted with 1 vol. of 0.16 m-potassium chloride in the absence (potassium chloride mince) and presence of added cofactor or glycolysable substrate, and the effects on the ultimate pH were examined. 2. Changes in the concentrations of glycogen and lactate and the concentrations of some phosphorus-containing fractions were determined in ox-muscle preparations. 3. Glycolysis ceased at appreciably higher pH in the potassium chloride mince than in undiluted mince. The inclusion of glycogen, ATP, ADP, NAD or magnesium chloride in the diluent had little effect on the ultimate pH of the diluted mince. 4. Lactic acid production continued at lower pH values in diluted mince containing added glucose 1-phosphate, fructose 1,6-diphosphate or glucose plus hexokinase than in potassium chloride mince. 5. The evidence points to failure of the phosphorylase step being responsible for the dilution effect.

Journal Article↗