The report uses density functional theory to address the mechanism of heme degradation by the enzyme heme oxygenase (HO) using a model ferric hydroperoxide complex. HO is known to trap heme molecules and degrade them to maintain iron homeostasis in the biosystem (Ortiz de Montellano, P. R. Acc. Chem. Res. 1998, 31, 543). The degradation is initiated by complexation of the heme, then formation of the iron-hydroperoxo species, which subsequently oxidizes the meso position of the porphyrin by hydroxylation, thereby enabling eventually the cleavage of the porphyrin ring. Kinetic isotope effect studies (Davydov, R.; Matsui, T.; Fujii, H.; Ikeda-Saito, M.; Hoffman, B. M. J. Am. Chem. Soc. 2003, 125, 16208) indicate that the mechanism is assisted by general acid catalysis, via a chain of water molecules, and that all the events occur in concert. However, previous theoretical treatments indicated that the concerted mechanism has a high barrier, much higher than an alternative mechanism that is initiated by O-O bond homolysis of iron-hydroperoxide (Sharma, P. K.; Kevorkiants, R.; de Visser, S. P.; Kumar, D.; Shaik, S. Angew. Chem. Int. Ed. 2004, 43,1129). The present contribution studies the stepwise and concerted acid-catalyzed mechanisms using H3O+(H2O)(n), n = 0-2. The effect of the acid strength is tested using the H4N+(H2O)(2) cluster and a fully protonated ferric hydroperoxide. All the calculations show that a stepwise mechanism that involves proton relay and O-O homolysis, in the rate-determining step, has a much lower barrier (> 10 kcal/mol) than the corresponding fully concerted mechanism. The best fit of the calculated solvent kinetic isotope effect, to the experimental data, is obtained for the H3O+(H2O)(2) cluster. The calculated cc-deuterium secondary kinetic isotope effect is inverse (0.95-0.98), but much less so than the experimental value (0.7). Possible reasons for this quantitative difference are discussed. Some probes are suggested that may enable experiment to distinguish the stepwise from the concerted mechanism.