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bioRxiv · 10.1101/227058

Catalytic potential and disturbance rejection of glycolytic kinases in the human red blood cell

Yurkovich, J. T.·Alcantar, M. A.·Haiman, Z. B.·Palsson, B. O.
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Abstract

The allosteric regulation of metabolic enzymes plays a key role in controlling the flux through metabolic pathways. The activity of such enzymes is traditionally described by allosteric rate laws in complex kinetic models of metabolic network function. As an alternative, we describe the fraction of the regulated enzyme that is in an active form by developing a detailed reaction network of all known ligand binding events to the enzyme. This fraction is the fundamental result of metabolic regulation as it represents the \"tug of war\" among the various regulators and substrates that determine the utilization of the enzyme. The active fraction corresponds to the utilization of the catalytic potential of the enzyme. Using well developed kinetic models of human red blood cell (RBC) glycolysis, we characterize the catalytic potential of its three key kinases: hexokinase (HEX), phosphofructokinase (PFK), and pyruvate kinase (PYK). We then compute their time-dependent interacting catalytic potentials. We show how detailed kinetic models of the management of the catalytic potential of the three kinases elucidates disturbance rejection capabilities of glycolysis. Further, we examine the sensitivity of the catalytic potential through an examination of existing personalized RBC models, providing a physiologically-meaningful sampling of the feasible parameter space. The graphical representation of the dynamic interactions of the individual kinase catalytic potential adjustment provides an easy way to understand how a robust homeostatic state is maintained through interacting allosteric regulatory mechanisms.

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Yurkovich, J. T., Alcantar, M. A., Haiman, Z. B., Palsson, B. O.. 2017-11-30. Catalytic potential and disturbance rejection of glycolytic kinases in the human red blood cell. https://doi.org/10.1101/227058

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