Human fumarase (FH), an enzyme in the citric acid cycle, is an essential component in this metabolic pathway that fuels cell throughout the human body. Previous research indicates that mutated FH enzyme (R444G) results in a decreased quality of life likely caused by the deficiency of FH function. The relationship between the structure and function of this mutation and how this impacts the decreased FH activity observed is not well understood. Circular dichroism, non-denaturing gels, and Michaelis-Menten kinetics were utilized to better understand the specific impacts that this mutation has on the structure and function of FH. These experiments demonstrated that this variant had quaternary structure, which is crucial to enzyme functionality. However, exploring several additive screens, which encompass chemical compounds that are similar to FH substate in shape and size, showed there were observed structural changes in the R444G mutation compared to the normal FH. Additionally, kinetic experiments showed this variant also had a 47.3-fold decrease in overall catalytic ability in comparison to the normal FH enzyme. This decreased catalytic ability results in a buildup of fumarate in cells which may cause decrease cellular functions such as DNA repair. Overall, this demonstrates the importance of conserved structure and function for essential metabolic enzymes in the human body and these mutations compromise this structure.