Title:Binding of Cimetidine to Balb/C Mouse Liver Catalase; Kinetics and Conformational Studies
Volume: 11
Issue: 1
Author(s): Mahboubeh Jahangirvand, Dariush Minai-Tehrani, Fatemeh Yazdi, Arash Minai-Tehrani and Nematollah Razmi
Affiliation:
Keywords:
Enzyme, inhibition, drug, hydrogen peroxide.
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.
