title: Binding of Cimetidine to Balb/C Mouse Liver Catalase; Kinetics and Conformational Studies.
abstract: Catalase is responsible for converting hydrogen peroxide (H2O2) into water and oxygen in cells. This enzyme has high affinity for hydrogen peroxide and can protect the cells from oxidative stress damage. Catalase is a tetramer protein and each monomer contains a heme group. Cimetidine is a histamine H2 receptor blocker which inhibits acid release from stomach and is used for gasterointestinal diseases. In this research, effect of cimetidine on the activity of liver catalase was studied and the kinetic parameters of this enzyme and its conformational changes were investigated. Cell free extract of mouse liver was used for the catalase assay. The activity of the catalase was detected in the absence and presence of cimetidine by monitoring hydrogen peroxide reduction absorbance at 240 nm. The purified enzyme was used for conformational studies by Fluorescence spectrophotometry. The data showed that cimetidine could inhibit the enzyme in a non-competitive manner. Ki and IC50 values of the drug were determined to be about 0.75 and 0.85 uM, respectively. The Arrhenius plot showed that activation energy was 6.68 and 4.77 kJ/mol in the presence and absence of the drug, respectively. Fluorescence spectrophotometry revealed that the binding of cimetidine to the purified enzyme induced hyperchromicity and red shift which determined the conformational change on the enzyme. Cimetidine could non-competitively inhibit the liver catalase with high affinity. Binding of cimetidine to the enzyme induced conformational alteration in the enzyme.
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Jahangirvand
authors.affiliation: BioResearch Lab, Faculty of Biological Sciences, Shahid Beheshti University, GC, Tehran, Iran. D_MTehrani@sbu.ac.ir.
authors.forename: Dariush
authors.initials: D
authors.lastname: Minai-Tehrani
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Yazdi
authors.forename: Arash
authors.initials: A
authors.lastname: Minai-Tehrani
authors.forename: Nematollah
authors.initials: N
authors.lastname: Razmi
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism*; D002927:Cimetidine / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding / Q000502:physiology; D011487:Protein Conformation
chemical_list: D002927:Cimetidine; D002374:Catalase