Abstract 2409 Connecting clinically observed metabolic deficiencies to protein structure and function

Human fumarase (FH), an enzyme in the citric acid cycle, is an essential component in this metabolic pathway that fuels cells throughout the human body. Single-site amino acid replacements of FH have led to two functionally deficient clinical outcomes. One outcome is the buildup of fumarate in cells which may cause decrease cellular functions such as DNA repair. Another observed outcome of FH dysfunction is a failure to thrive and often premature death. Previous clinical research indicates that a single-site replacement of arginine → → glycine at position 444 (R444G) falls into the failure to thrive category.