<p>Vitamin B12 is essential for maintaining nervous system health and is involved in important methylation reactions, DNA synthesis, and the hydrogenation of various biosubstrates. Therefore, understanding the biochemical mechanisms involving vitamin B12 during patient treatment is crucial for neurochemistry and medicine. Since studying these processes in vivo is very challenging experimentally, theoretical studies based on reliable models can provide valuable insights into the biochemistry of vitamin B12-dependent processes. For this purpose, multiconfigurational geometric optimization calculations were performed on the forms of vitamin B12 administered to patients during their interaction with active biosubstrates at the final stage of absorption in the human body. CASSCF(14,13) geometry optimization of one form of vitamin B12 and models of glutathione, NADPH, FMN, or FAD shows that all forms interact with these agents by breaking Co-C or Co-O bonds and accepting one electron or significant electron density, increasing electron transfer toward the end of the reactions. The cleavage of Co-C and Co-O bonds and the substantial transfer of electron density occur under the influence of a strong pseudo-Jahn-Teller effect between two intermolecular HOMO-LUMO orbitals, starting from the very beginning of the reactions. Electronic structure calculations show that cyanocobalamin does not interact with three potential substrates that could convert it into a form of vitamin B12 easily absorbed by the human body and capable of participating in the turnover of active vitamin B12 forms. The only substrate that converts cyanocobalamin into a biologically acceptable form is glutathionyl. This result aligns with experimental data from studies of patients with vitamin B12 deficiency.</p>