Catalase is a crucial antioxidant enzyme that protects life against detrimental effects of H2O2 by disproportionating it into water and molecular oxygen. Effect of proline as a compatible and histidine as a non compatible osmolyte on the electron transferring and midpoint potential of catalase has been investigated. Proline increases the midpoint potential (Delta E-m > 0), therefore causing the Delta G(ET), to be less positive and making the electron transfer reaction more facile whereas histidine decreases the E-m (Delta E-m < 0) and consequently a causes a pronounced increase in Delta G(ET), thereby rendering the electron transfer reaction less efficient. These results indicate the inhibitory effect of histidine evident by a -37% decrease in the cathodic peak current compared to 16% increase in the case of proline indicative of activation. The insight paves the tedious way towards our ultimate goal of elucidating a correlation between biological activity and electron transferring. (C) 2013 Elsevier Ltd. All rights reserved.