Background: In patients with the Congenital Sucrase-Isomaltase Deficiency (CSID), who
lack intestinal sucrase-isomaltase enzyme, a suspension of yeast sucrase is applied as a drug to
compensate the enzyme deficiency. While antipsychotic drugs are used for the treatment of
schizophrenia, administering multiple drugs at the same time may counteract each other.
Methods: In this study, the interaction between trifluoperazine and haloperidol as antipsychotic drugs
on oral drug yeast sucrase was investigated. In this regard, the kinetic parameters of enzyme were
determined in the presence or absence of the drugs. The kinetic parameters of the drugs such as Ki
and IC50 were also calculated. Lineweaver - Burk plot was used to reveal the type of inhibition.
Results: The results showed that both drugs could reduce sucrase activity and decrease the Vmax of
the enzyme by non-competitive inhibition. The IC50 and Ki values of the drugs were determined to be
0.7 and 0.068 mM and 0.45 and 0.063 mM for haloperidol and trifluoperazine, respectively. The
results suggested that trifluoperazine binds to the enzyme with higher affinity than haloperidol.
Fluorescence measurement was used for conformational investigations of the drugs and sucrase
interaction. It was shown that the drugs bind to free enzyme and enzyme-substrate complex which are
accompanied with hyperchromicity. This suggests that tryptophan residues of the enzyme transferred
to hydrophobic medium after binding of the drugs to the enzyme.
Conclusion: The finding of this research revealed that both trifluoperazine and haloperidol could
inhibit sucrase in non-competitive manner. The kinetic parameters and conformational changes due to
binding of trifluoperazine to the enzyme were different from that of haloperidol.