ABSTRACT
Control of glucose metabolism in rat liver under different glucose concentrations was studied. Flux Control Coefficients of glucokinase, glucose 6-phosphate isomerase and phosphofructokinase were determined by the 'shortening and enzyme titration' method. Results obtained show that glucose concentration in liver can play an important role in control of liver glycolysis by enhancing the Flux Control Coefficient of phosphofructokinase. Possible physiological significance of this fact is discussed.
Subject(s)
Glucokinase/metabolism , Glucose/metabolism , Glycolysis , Liver/metabolism , Phosphofructokinase-1/metabolism , Animals , Female , In Vitro Techniques , Liver/enzymology , Models, Theoretical , Rats , Rats, Inbred StrainsABSTRACT
1. The transition state of the glycolytic pathway, under FDP saturating conditions, from no ADP to ADP-saturating levels, is studied in a metabolic model in vitro obtained from rat skeletal muscle. 2. When ADP is absent from the reaction mixture a steady state for NADH concentration is observed. After ADP addition, a new steady state is reached. The transition state from the first steady state to the second one shows a pulse of NADH. Both the profile and the size of this pulse depend on the enzyme concentration. 3. A kinetic model of the lower part of glycolysis (after PFK reaction) is proposed, and this is described by a set of first order coupled nonlinear differential equations. The results obtained through stability analysis and numerical integration of these equations agree with the experimental ones. 4. The possible role of the above mentioned transition state on the transmitter mechanism of glycolytic oscillations from PFK to the lower part of the glycolysis is discussed.
Subject(s)
Fructosediphosphates/metabolism , Glycolysis , Hexosediphosphates/metabolism , Adenosine Diphosphate/metabolism , Algorithms , Animals , Kinetics , Male , Models, Biological , NAD/metabolism , Rats , Rats, Inbred StrainsABSTRACT
1. Transient response of the glycolytic system, after phosphofructokinase reaction, to ADP input was studied in a metabolic model in vitro, obtained from rat muscle. 2. Under ADP addition to the system, NADH concentration is largely enhanced to be decreased later, showing a very characteristic pulse whose parameters can be used to describe some features of the transition state. 3. NADH pulse was repeatedly obtained by means of successive ADP inputs to the system. 4. The effect of different variables on NADH pulse was studied, these results suggesting a possible role for different steps on this response. 5. The possible relation between the pulse of NADH and oscillatory behaviour of glycolysis is discussed.
Subject(s)
Adenosine Diphosphate/pharmacology , Glycolysis/drug effects , Muscles/metabolism , Phosphofructokinase-1/metabolism , Animals , Kinetics , Muscles/drug effects , NAD/metabolism , NAD/pharmacology , RatsABSTRACT
A metabolic system in vitro, which converts fructose 1,6-biphosphate into the two alternative products, lactate and glycerol phosphate, was designed to study the distribution of metabolic fluxes and, specifically, the control of glycerol phosphate production rate in rat muscle extract. Experiments were carried out at several protein concentrations by dilution of rat muscle extract, showing non-linear behaviours of flux versus protein concentration. These were hyperbolic for glycerol phosphate and logarithmic for L-lactate. The influence of the flux towards any alternate product on the rate giving the other was studied by stimulation of each. Results obtained show that in this system, flux towards glycerol phosphate is not affected by lactate production and the same occurs for the contrary case. Glycerol phosphate dehydrogenase seems to be the only enzyme in this system whose activity controls the flux towards glycerol phosphate.
