Protein-Metobolite Interactions in the Urea Cycle

The proper regulation of cellular metabolism is essential for overall health. When disruptions in metabolism occur, it can lead to the development of complex diseases, such as cancer. A highly dysregulated pathway that occurs in cancers is within the urea cycle. Located in the liver, the urea cycle serves as a detoxification mechanism to rid the body of the toxic byproduct of metabolism, ammonia. In the context of cancer, instead of using this cycle to use ammonia to excrete urea, it is rewired to support the synthesis of building blocks that allow for rapid cell growth.

Another classic hallmark of cancer development is increased breakdown of sugar through the metabolic pathway, glycolysis. This increased flux through glycolysis increases the levels of glycolytic intermediates that serve as substrates for important chemical processes. Because these pathways are dysregulated in the context of cancer, understanding how they are regulated is essential. Much of the time, metabolic pathways are studied in isolation, when in reality they all work together for cell processes to take place properly.

This project focuses on uncovering the novel relationship between glycolysis and the urea cycle during cancer development, and how this ultimately drives regulation of these metabolic pathways. We aim to understand how these interactions ultimately regulate metabolism and promote cancer at the molecular level using different biological approaches. Preliminary data demonstrates that a glycolytic intermediate interacts and regulates the activity of a urea cycle enzyme. Further investigations will elucidate how this occurs, and what metabolic contexts favor this interaction.