Evaluation of the toxicity of 5-fluorouracil on three digestive enzymes from the view of side effects

Among the side effects of 5-fluorouracil (5-FU), the performance of the gastrointestinal reactions is faster and more obvious than others. In this work, the effects of 5-FU on the activities and conformational structures of the important digestive enzymes including α-amylase, pepsin and trypsin were studied to analyze the mechanism of the gastrointestinal adverse effects causing by 5-FU binding. The results showed that the enzymatic activity of pepsin was obviously reduced by the presence of 5-FU that bound directly to the enzyme activity cavity site. The molecular modeling and fluorescence quenching data indicated that the hydrophobic, polar and hydrogen bonding forces were involved in the ground state complex formation between proteases and 5-FU. In addition, 5-FU changed the tertiary structures of α-amylase, pepsin, and trypsin.