The metabolic pathways that shape how our bodies use nutrients and energy are under constant adjustment, with metabolites pay a key role in managing their function and activity. There are thousands of metabolites inside our cells, and surprisingly little is known about how most of them interact with other cellular components, even though when these interactions with proteins are disrupted, it can leave us more vulnerable to disease. New technology developed by U of U Health science faculty Jared Rutter, PhD, and Kevin Hicks, PhD, is changing that, allowing researchers to systematically identify which metabolites interact with particular proteins.
Rutter, Hicks, and their team used their platform, which they named MIDAS, to test for interactions between metabolites and the enzymes involved in carbohydrate metabolism. They found more than 800, many of which were previously unknown to researchers. With further experiments, they figured out exactly how several of the metabolites interact with enzymes to increase or dampen their activity. Their findings don’t just help explain how healthy cells work. By revealing specific ways in which metabolic pathways can be modulated, they suggest how drug developers might target the same pathways to treat disease. Atavistik, a company cofounded by Rutter, builds on this knowledge to explore potential treatments for cancer and metabolic diseases.
References:
Protein-metabolite interactomics of carbohydrate metabolism reveals regulation of lactate dehydrogenase. Hicks KG, Cluntun AA, Schubert HL, Hackett SR, Berg JA, Leonard PG, Ajalla Aleixo MA, Zhou Y, Bott AJ, Salvatore SR, Chang F, Blevins A, Barta P, Tilley S, Leifer A, Guzman A, Arok A, Fogarty S, Winter JM, Ahn H-C, Allen KN, Block S, Cardoso IA, Ding J, Dreveny I, Gasper C, Ho Q, Matsuura A, Palladino MJ, Prajapati S, Sun P, Tittmann K, Tolan DR, Unterlass J, VanDemark AP, Vander Heiden MG, Webb BA, Yun C-H, Zhap P, Wang B, Schopfer FJ, Hill CP, Nonato MC, Muller FL, Cox JE, and Rutter J. Science 2023 Mar 10;379(6636):996-1003. doi: 10.1126/science.abm3452.
