title: Interaction of Antipsychotic Drugs with Sucrase, Kinetics and Structural Study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: BioResearch Lab, Faculty of Biological Sciences & Technology, Shahid Beheshti University, G.C. Tehran, Iran.
authors.forename: Narges
authors.initials: N
authors.lastname: Jafari
authors.affiliation: BioResearch Lab, Faculty of Biological Sciences & Technology, Shahid Beheshti University, G.C. Tehran, Iran.
authors.forename: Helia
authors.initials: H
authors.lastname: Dehganpour
authors.affiliation: BioResearch Lab, Faculty of Biological Sciences & Technology, Shahid Beheshti University, G.C. Tehran, Iran.
authors.forename: Nava
authors.initials: N
authors.lastname: Ghavanini
authors.affiliation: Protein Research Center, Shahid Beheshti University, Tehran, Iran.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Mollasalehi
authors.affiliation: BioResearch Lab, Faculty of Biological Sciences & Technology, Shahid Beheshti University, G.C. Tehran, Iran.
authors.forename: Dariush
authors.initials: D
authors.lastname: Minai-Tehrani
mesh_terms: D000494:Allosteric Regulation; D014150:Antipsychotic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D056947:Enzyme Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D006220:Haloperidol / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D011487:Protein Conformation; D018570:Risk Assessment; D013329:Structure-Activity Relationship; D013393:Sucrase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014268:Trifluoperazine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D014150:Antipsychotic Agents; D004791:Enzyme Inhibitors; D014268:Trifluoperazine; D013393:Sucrase; D006220:Haloperidol
keywords: Enzyme; conformational changes; drug; inhibition; kinetics; schizophrenia