Cytochrome c is a hemeprotein that plays vital roles in the cells. In the respiratory chain, bound to the inner mitochondrial membrane, cytochrome c act as an electron carrier and under specific stimulus can detach from that membrane and trigger the apoptosis in cytosol. Several works have related the influence of the redox state of the heme iron on the ability of cytochrome c to activate the apoptosis. Data from our laboratory have demonstrate that the reduction of the cytochrome c heme iron by diphenylacetaldehyde and the neutral radical of methylene blue is dependent on the interaction of the reducing agent with two tyrosine residues (Tyr67 and Tyr74). In the case of diphenylacetaldehyde the reaction is favored when one tyrosine residue is protonated and other is deprotonated and thus, the reducing process is pH-dependent with the optimal pH = 10.0. On the other hand, cytochrome c is reduced by thiol groups in a pH-independent manner. In this work, we investigated comparatively the effect of pH on the reduction of cytochrome c by two non-thiolic biological compounds, glucose, galactose and b-NADH. In the case of monosaccharides the pH curve for the reduction process exhibits optimal pH around 9.0 and the complete cytochrome c reduction is not attained. The reaction is accompanied by oxygen consumption suggesting the formation of free radicals intermediates. When b-NADH was used as the reducing agent, the optimal pH was determined as being 7.0. This result suggests that the cytochrome c reduction by b-NADH is not dependent on the ionization of tyrosine residues. However, the optimal pH value for this reducing agent is the pH value found in cytosol and suggests that b-NADH could play a role in the cytochrome c reduction in this cell compartment. The investigation of the reaction pathway for these substrates is our scope herein.