Regulation of glycolysis by adenosine diphosphate in Pisum sativum

The role of ADP in controlling glycolysis has been examined in a soluble extract of germinating pea seeds. A shortage of ADP appears to retard glycolysis principally by restricting the conversion of phosphopyruvate to pyruvate rather than by restricting formation of phosphoglycerate. Upon addition of ADP to the extract there is an immediate decrease in the concentration of phosphopyruvate accompanied by an increase in pyruvate. Apparently the pyruvate-kinase step shows the most marked response to fluctuations in ADP availability. The glycolytic response to ADP depends on the concentration of ATP magnesium ions. The relation of magnesium-ion availability to adenine-nucleotide control of glycolysis is discussed.     

Fibrinogen and fibrinogen-fibrin degradation products in experimental African trypanosomiasis

Fibrinogen and fibrinogen/fibrin degradation products in experimental African trypanosomiasis. International Journal for Parasitology4: 143–151. Studies have been carried out on some components of the fibrinolytic system of rabbits infected with two strains of Trypanosoma (Trypanozoon) brucei. Significant increases in fibrinogen/ fibrin degradation products (FDP) occur with a peak of activity 14–21 days after infection. Plasma fibrinogen concentrations increase during the infection. Measurement of plasminogen concentrations and experimental inhibition of plasmin by drugs suggests that plasminogen is being activated during the infection giving rise to FDP production. Administration of the trypanocidal drug Mel B to infected rabbits did not cause a rapid change in FDP levels. The results suggest an increased synthesis of fibrinogen. This, together with the increased amount of FDP, may be indicative of an increased fibrinolytic activity suggesting the formation of microthrombi in the circulation.     

Changes in energy metabolism due to anthelmintics in Fasciola hepatica maintained in vitro

The effects of rafoxanide (RFX), nitroscanate (NSC) and mebendazole (MBZ) on oxidative pathways in whole F. hepatica maintained in a simple salt solution have been examined. The anthelmintics did not alter glucose uptake or glycogen mobilization. NSC and RFX depressed ATP and increased AMP levels. MBZ behaved similarly at first, but later depressed the total adenine nucleotides. All three drugs influenced end product formation, increasing it initially, although by different mechanisms. With NSC, early increases in lactate and acetate excretion were later abolished. With RFX, there was an initial increased production of acetate and propionate. Later, excretion of propionate was reduced and that of succinate was increased. MBZ also increased succinate excretion, but to a much greater extent. In addition, it inhibited lactate production. A number of effects of the drugs on the internal concentrations of metabolic intermediates are described. The mechanisms of action of the drugs are discussed.     

A path analysis of the causal relationships between red cell glycolytic intermediates, ADP and ATP in sickle cell anemia

The statistical relationships among the glycolytic intermediates (GI)) of the Embden-Meyerhof pathway, adenine nucleotides (ANs) and various hematological measures were estimated for 34 sickle cell anemia patients. Heterogeneity in linear and quadratic regressions of hemoglobin and hematocrit, both singly and jointly, on the GI and AN variables implied 1) that any single formula to standardize optical density measures of the GIs and ANs on a per gram hemoglobin or per liter cell water basis would not uniformly remove hemoglobin and hematocrit effects: 2) that ignoring significant hematological effects could bias the estimates of correlation among GIs and ANs; and 3) that hemoglobin and hematocrit measures do not reflect the same source of variability. The correlations among the GIs and ANs, after adjustment for hematological variability, were analyzed by path analysis to determine which of five proposed path models for cause and effect relationships were compatible with the data. AMP had a greater influence on ADP (coefficient of determination (CD) = 23%) than all the GIs together, while G6P and ADP influenced ATP variability the most (CD = 33% and 12%). The contributions of unknown factors to ADP and ATP variability were large for all models (CD = 56--77%) possibly due to stress of sickle cell disease. The path model with AMP and the four GIs (G6P, F6P, FDP, DHAP) influencing ADP variation, and the same GIs and ADP influencing ATP was the model most compatible with the data.     

The response of oscillating glycolysis to perturbations in the NADH/NAD system: a comparison between experiments and a computer model.

The glycolytic pathway is described by a set of coupled non linear differential equations of first order with respect to time. The individual terms of these equations consist of enzyme velocities assuming a steady state hypothesis for the enzymatic forms. These are specified and the system is solved numerically. Oscillations are explained by interaction of PFK with the adenylate system. The conditions for the occurrence of oscillations are tested in a series of computer runs. The phase relations between intermediates of the model agree with those found in yeast cells. As an application of the model the disturbation of oscillations by the addition of acetaldehyde is simulated. The predictions of the model agree with experimental results.     

Fructose-1,6-diphosphate as an in vitro and in vivo anti-alcohol agent in the rat

Fructose-1, 6-diphosphate (FDP) decreases the effect of ethanol on Ca++ entry and inhibits the ethanol-stimulated phosphate efflux in rat heart slices. FDP also inhibits the ethanol-stimulated [36Cl-]-uptake by rat brain microvesicles and affects the isolated GABA-receptor in a way opposite to that of ethanol. The in vivo effects of FDP include a dose-dependent decrease in ethanol-induced gastric ulcers and a decrease in the serum transaminase levels raised by chronic ethanol administration. Other central actions of ethanol such as diuresis, narcosis, dependence and withdrawal symptoms are also counteracted by FDP.     

The metabolic integrity of Fasciola hepatica during in vitro maintenance

Levels of metabolic intermediates and end products in F. hepatica after 24 and 48 h in Hédon-Fleig salt solution with added glucose were compared with levels obtained immediately on removal from the host. Glycogen levels dropped initially, probably due to the expulsion of eggs; thereafter they remained constant. Internal glucose concentrations increased as the parasites equilibrated with the medium. Other changes in internal pool sizes were consistent with regulation to the in vitro conditions. ATP levels increased; ATP/ADP ratios were maintained. Comparisons of mass action ratios and equilibrium constants suggest that hexokinase, pyruvate kinase and phosphofructokinase are regulatory. Output of excretory products approached linearity; from the calculated regressions the proportions of lactate, acetate and propionate were 1: 2: 4. The implications for metabolic regulation in F. hepatica are briefly discussed, and it is concluded that, for at least 48 h in vitro, energy metabolism is not adversely affected.