A Comprehensive Computational Study on the Thermodynamics and Kinetics of Tetrahydrobiopterin Regeneration Process.
Autor: | Samanta S; Department of Chemistry, Indian Institute of Science Education and Research (IISER), Tirupati, India., Mondal P; Department of Chemistry, Indian Institute of Science Education and Research (IISER), Tirupati, India.; Center for Atomic, Molecular and Optical Sciences and Technologies, Indian Institute of Science Education and Research (IISER), Tirupati, India. |
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Jazyk: | angličtina |
Zdroj: | Chemphyschem : a European journal of chemical physics and physical chemistry [Chemphyschem] 2024 Jun 11, pp. e202400401. Date of Electronic Publication: 2024 Jun 11. |
DOI: | 10.1002/cphc.202400401 |
Abstrakt: | One of the most crucial enzymatic cofactors in the human body is tetrahydrobiopterin, which is acquired through biological synthesis and self-regeneration. During this regenerative process, it undergoes oxidation, deprotonation, further oxidation, and subsequent deprotonation, resulting in the formation of quinonoid-dihydrobiopterin, which then undergoes tautomerization to yield dihydrobiopterin. This study presents the thermodynamic and kinetic properties associated with each stage of the regeneration process using theoretical calculations. The redox potentials for oxidation steps and the pKa values for deprotonation steps are determined employing the Born-Haber cycle and the direct change of free energy in implicit solvent models. The redox metabolites are characterized and confirmed from their calculated absorption spectra using the time-dependent density functional theory method. For the tautomerization steps, an IRC calculation is executed, and rate constants are computed using Eyring's Transition State Theory (TST). The tunnelling probability of the H atom during the tautomerization process is incorporated using Wigner's tunnelling correction in the calculation of the rate constant. Notably, we identify the N3 atom as the most probable deprotonation site for H (© 2024 Wiley-VCH GmbH.) |
Databáze: | MEDLINE |
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