Quantum Chemical Study of the Mechanism of Action of Vitamin K Carboxylase (VKC). IV. Intermediates and Transition States

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• 作者：Charles H. Davis ; David Deerfield II ; Darrel W. Stafford ; Lee G. Pedersen
• 刊名：Journal of Physical Chemistry A
• 出版年：2007
• 出版时间：August 9, 2007
• 年：2007
• 卷：111
• 期：31
• 页码：7257 - 7261
• 全文大小：128K
• 年卷期：v.111,no.31(August 9, 2007)
• ISSN：1520-5215

文摘

We studied proposed steps for the enzymatic formation of G SRC="/images/gifchars/gamma.gif" BORDER=0 >-carboxyglutamic acid by density functionaltheory (DFT) quantum chemistry. Our results for one potentially feasible mechanism show that a vitamin Kalkoxide intermediate can abstract a proton from glutamic acid at the ges/gifchars/gamma.gif" BORDER=0 >-carbon to form a carbanion andvitamin K epoxide. The hydrated carbanion can then react with CO₂ to form ges/gifchars/gamma.gif" BORDER=0 >-carboxyglutamic acid.Computations at the B3LYP/6-311G** level were used to determine the intermediates and transition statesfor the overall process. The activation free energy for the gas-phase path is 22 kcal/mol, with the rate-limiting step for the reaction being the attack of the carbanion on CO₂. Additional solvation studies, however,indicate that the formation of the carbanion step can be competitive with the CO₂ attack step in high-dielectricsystems. We relate these computations to the entire vitamin K cycle in the blood coagulation cascade, whichis essential for viability of vertebrates.