Related Experiment Video
Updated: Jul 30, 2025

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
Identifiability of enzyme kinetic parameters in substrate competition: a case study of CD39/NTPDase1
Anna N McGuinness1, Aman Tahir1, Nadia R Sutton1,2,3
1Division of Cardiovascular Medicine, Department of Medicine, Michigan Medicine, Ann Arbor, MI, USA.
Abstract:
CD39 (NTPDase1-nucleoside triphosphate diphosphohydrolase 1) is a membrane-tethered ectonucleotidase that hydrolyzes extracellular ATP to ADP and ADP to AMP. This enzyme is expressed in a variety of cell types and tissues and has broadly been recognized within vascular tissue to have a protective role in converting "danger" ligands (ATP) into neutral ligands (AMP). In this study, we investigate the enzyme kinetics of CD39 using a Michaelis-Menten modeling framework. We show how the unique situation of having a reaction product also serving as a substrate (ADP) complicates the determination of the governing kinetic parameters. Model simulations using values for the kinetic parameters reported in the literature do not align with corresponding time-series data. This dissonance is explained by CD39 kinetic parameters previously being determined by graphical/linearization methods, which have been shown to distort the underlying error structure and lead to inaccurate parameter estimates. Modern methods of estimating these kinetic parameters using nonlinear least squares are still challenging due to unidentifiable parameter interactions. We propose a workflow to accurately determine these parameters by isolating the ADPase and ATPase reactions and estimating the respective ADPase parameters and ATPase parameters with independent data sets. Theoretically, this ensures all kinetic parameters are identifiable and reliable for future prospective model simulations involving CD39. These kinds of mathematical models can be used to understand how circulating purinergic nucleotides affect disease etiology and potentially inform the development of corresponding therapies.
More Related Videos
Related Concept Videos
Introduction to Enzyme Kinetics
The experimenter can then plot the initial reaction rate or velocity (Vo) of a given trial against the substrate concentration ([S]) to obtain a graph of the reaction properties. For many enzymatic reactions involving a...
Enzyme Kinetics
Scientists typically study enzyme kinetics with a fixed amount of enzyme in the controlled environment of a test tube. When more reactant, or substrate, is...
Turnover Number and Catalytic Efficiency
Chymotrypsin is a pancreatic enzyme that breaks down proteins during digestion....
Catalytically Perfect Enzymes
Most enzymes...
Enzyme Inhibition
Enzymes
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...

