Metal oxides as a rule oxidize and oxygenate substrates via the Mars-van Krevelen mechanism. A well-defined alpha-Keggin polyoxometalate, H5PV2Mo10O40, can be viewed as an analogue of discrete structure that reacts via the Mars van Krevelen mechanism both in solution and in the gas phase. Guided by previous experimental observations, we have studied the key intermediates on the reaction pathways of its reduction by various compounds using high-level DFT calculations. These redox reactions of polyoxometalates require protons, and thus such complexes were explicitly considered. First, the energetics of outer-sphere proton and electron transfer as well as coupled proton and electron transfer were calculated for seven substrates. This was followed by identification of possible key intermediates on the subsequent reaction pathways that feature displacement of the metal atom from the Keggin structure and coordinatively unsaturated sites on the H5PV2Mo10O40 surface. Such metal defects are favored at vanadium sites. For strong reducing agents the initial outer-sphere electron transfer, alone or possibly coupled with proton transfer, facilitates formation of metal defects. Subsequent coordination allows for formation of reactive ensembles on the catalyst surface, for which the selective oxygen-transfer step becomes feasible. Weak reducing agents do not facilitate defect formation by outer-sphere electron and/or proton transfers, and thus formation of metal defect structures prior to the substrate activation is suggested as an initial step. Calculated geometries and energies of metal defect structures support experimentally observed intermediates and demonstrate the complex nature of the Mars-van Krevelen mechanism.