Apparent aberrancy in the kinetics of intracellular metabolism of a single substrate by two enzymes. An alternative explanation for anomalies in the kinetics of sulfation and glucuronidation.
The intracellular metabolism of a substrate by two simultaneous, competing metabolic routes in intact isolated cells is analyzed by use of a kinetic model. The following assumptions were made: 1) uptake and back-transport to the medium of the unchanged substrate are symmetrical and linear with the extracellular and intracellular concentrations, respectively; 2) two metabolic routes convert the substrate simultaneously, according to Michaelis-Menten kinetics, from the same intracellular substrate pool. Equations describing transport and metabolism of the substrate are derived for a steady-state situation. It is shown that the intracellular substrate concentration increases more than proportionally with the extracellular concentration when the metabolic reaction with high affinity becomes saturated. This causes the conversion via unsaturated routes (low-affinity conversion) also to increase more than proportionally. Thus, the kinetics of metabolism show anomalous behavior when related to the extracellular substrate concentration. Furthermore, the model suggests that the apparent KM value of a metabolic conversion in an intact cell, expressed and determined as the extracellular substrate concentration at half the maximal velocity of the reaction, is not a true Michaelis-Menten constant; its value is determined by the kinetic parameters of competing reactions. Some results from the literature on anomalous behavior of sulfation and glucuronidation in different preparations have been analyzed with our model; a good agreement was obtained between experimental results and values determined by extrapolation according to our model.
D001692:Biological Transport; D005965:Glucuronates / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D013464:Sulfuric Acids / Q000378:metabolism*
D005965:Glucuronates; D004364:Pharmaceutical Preparations; D013464:Sulfuric Acids