APPARENT ABERRANCY IN THE KINETICS OF INTRACELLULAR METABOLISM OF A SINGLE SUBSTRATE BY 2 ENZYMES - AN ALTERNATIVE EXPLANATION FOR ANOMALIES IN THE KINETICS OF SULFATION AND GLUCURONIDATION

  • 1 January 1982
    • journal article
    • research article
    • Vol. 10  (4) , 330-335
Abstract
The intracellular metabolism of a substrate by 2 simultaneous, competing metabolic routes in intact isolated cells is analyzed by use of a kinetic model. It was assumed that: uptake and back-transport to the medium of the unchanged substrate are symmetrical and linear with the extracellular and intracellular concentrations, respectively; and 2 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. 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. The kinetics of metabolism show anomalous behavior when related to the extracellular substrate concentration. 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 were analyzed with the model; a good agreement was obtained between experimental results and values determined by extrapolation according to the model. [Implications for drug metabolism are discussed.].