Enzyme mutations often lead to dysfunction and catalytic efficiency changes, which can cause diseases such as cancer. Here two enzymes were studied, isocitrate dehydrogenase (IDH) and receptor tyrosine kinase Tie2 (Tie2). IDH enzymes are a class of metabolic dehydrogenase that include IDH1 and IDH2. IDH1 localizes to the cytosol and peroxisomes while IDH2 exists in the mitochondria. IDH1 and IDH2 are both homodimeric enzymes that are responsible for the reversible NADP+- and Mg2+-dependent conversion of isocitrate (ICT) to α-ketoglutarate (α-KG). Mutations in IDH1 and IDH2 have been found in gliomas, secondary glioblastomas and acute myeloid leukemia (AML). One mutation hot spot for IDH is at residue R132 or R172 for IDH1 and IDH2, respectively. These IDH1/2 mutants can produce oncometabolite (R)-2-hydroxyglutarate (D2HG) which is known as the neomorphic reaction. The second enzyme studied, Tie2, is a member of the receptor tyrosine kinase (RTK) family, which plays an important role in maintaining healthy vascular formation and development. The most common germline mutation, R849W Tie2, causes venous malformations. In this work, I used two expression systems and kinetic methods to investigate the differences in catalytic efficiency among the WT and mutants. For IDH1, two mutants (R132Y and R132E) were studied and they both demonstrated a slower normal reaction rate while favoring the neomorphic reaction. Also, R132Y IDH1 showed a higher catalytic efficiency for both normal and neomorphic reaction than R132E IDH1. For Tie2, though there was no major difference of the catalytic efficiency between WT and R849W Tie2, the kcat value of R849W was 3.2-fold higher than that measured for WT. These results provide insights on the molecular mechanism of these enzymes. The long-term goal of this work is to identify the relationship between catalytic efficiency and the severity of phenotypes in vitro and in vivo observed in IDH- and Tie2-related disorders.