Modafinil as an Inhibitor of Glycogen Phosphorylase b 

Voiceover

Presenter(s)

Allison Babbit

Abstract or Description

Glycogen phosphorylase b (GPb) is responsible for the breakdown of glycogen into glucose-1-phosphate and is regulated by numerous effectors in response to changes in cellular states. The inactive GPb is converted to its active form, GPa, through phosphorylation, a process that is enhanced by molecules like AMP and epinephrine. This study aims to investigate how AMP, epinephrine, and modafinil modulate GPb activity, providing broader insights into metabolic regulation and potential therapeutic applications. GPb activity was measured in the reverse reaction, using G1P as the substrate and inorganic phosphate as the product to determine kinetic constants. Using spectrophotometric enzyme kinetics assays, the effect of AMP and epinephrine on GPb, which are known activators of GPb, was measured. Modafinil, a wakefulness-promoting agent that influences dopamine and catecholamine signaling, was also tested for its effects on GPb. Both epinephrine and AMP were proven to be activators of GPb, and Modafinil was shown to be a competitive inhibitor of GPb, as an increase in modafinil concentration resulted in an increase in Km for an inhibition test. This could open avenues for investigating how modafinil influences glycogen storage particularly in individuals with metabolic conditions.

Mentor

Dr. Roberto DeGuzman