Julia Zuercher

By William & Mary

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Connecting Energy Metabolism and Neurodegeneration: Pyruvate Kinase and Oxidative Stress

Pyruvate kinase (PK) is a key enzyme in glycolysis, the first step to converting sugar into energy. PK has sulfur-containing amino acids called cysteines that are key for its regulation and function. Normally in cells, these cysteines are reduced, which means that each sulfur is bound to a hydrogen atom. This gives the enzyme a specific structure and function. Sometimes, however, other processes in the cell err and produce oxygen molecules with an extra electron, called reactive oxygen species (ROS), which can cause significant damage. Stress caused by these oxidants increases with age and has been linked to cancer and neurodegenerative diseases. For PK, the strong attractive forces of an oxidant will take the hydrogen away from sulfur atoms in cysteines. To compensate for the loss, two cysteines will interact and form a disulfide bridge, which changes the shape of PK and potentially affects the enzyme’s ability to function. This project seeks to determine the extent to which an ROS changes the function of PK and whether or not a reduced environment could undo this damage. It is possible that PK protects itself and shields more sensitive molecules from oxidative damage, such as those involved in Alzheimer’s and Parkinson’s diseases.

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