Determining the kinetic parameters of CD39 – an enzyme with multiple substrates and products – UROP Spring Symposium 2021

Determining the kinetic parameters of CD39 – an enzyme with multiple substrates and products

Anna McGuinness


Pronouns: She/Her

Research Mentor(s): Nadia Sutton, Assistant Professor
Research Mentor School/College/Department: Internal Medicine- Cardiology, Michigan Medicine
Presentation Date: Thursday, April 22, 2021
Session: Session 2 (11am – 11:50am)
Breakout Room: Room 14
Presenter: 3

Event Link


Enzyme kinetics are often summarized in the form a Michaelis-Menten type model with parameters representing the maximum velocity of the reaction and concentration of substrate where the reaction is at half of the maximum velocity. Traditionally, these parameters can be experimentally determined by using linear regression between the reciprocal of the rate of reaction and reciprocal of the concentration of substrate (ex: Woolf-Augustinsson-Hofstee plot, Lineweaver-Burk plot). Implicit within these methods is the assumption that the enzyme of interest has a single substrate and single product. For enzymes such as CD39 with multiple substrates and products, these methods are likely inappropriate to accurately determine their Michaelis-Menten parameters. CD39 is an ectonucleotides that can hydrolyze ATP and ADP into ADP and AMP, respectively. In this study, we develop and analyze the behavior of a model of CD39 enzyme kinetics accounting for substrate competition. Simulations with our model using Michaelis-Menten parameters for CD39 ATPase and ADPase activity determined by the Woolf-Augustinsson-Hofstee method do not acutely explain kinetic data of ATP, ADP, and AMP concentrations reported by Kukukski et al. Using non-linear parameter estimation, we determine parameters for our CD39 model that accurately capture the kinetic data. Uncertainty in our model predictions is quantified using 95% confidence and prediction intervals.

Authors: Andrew Marquis, Anna McGuinness, Aman Tahir
Research Method: Laboratory Research

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