Reyes Archie C, Amyes Tina L, Richard John P
Department of Chemistry, University at Buffalo, SUNY, Buffalo, New York 14260-3000, USA.
Org Biomol Chem. 2017 Oct 31;15(42):8856-8866. doi: 10.1039/c7ob01652b.
There is no consensus of opinion on the origin of the large rate accelerations observed for enzyme-catalyzed hydride transfer. The interpretation of recent results from studies on hydride transfer reactions catalyzed by alcohol dehydrogenase (ADH) focus on the proposal that the effective barrier height is reduced by quantum-mechanical tunneling through the energy barrier. This interpretation contrasts sharply with the notion that enzymatic rate accelerations are obtained through direct stabilization of the transition state for the nonenzymatic reaction in water. The binding energy of the dianion of substrate DHAP provides 11 kcal mol stabilization of the transition state for the hydride transfer reaction catalyzed by glycerol-3-phosphate dehydrogenase (GPDH). We summarize evidence that the binding interactions between (GPDH) and dianion activators are utilized directly for stabilization of the transition state for enzyme-catalyzed hydride transfer. The possibility is considered, and then discounted, that these dianion binding interactions are utilized for the stabilization of a tunnel ready state (TRS) that enables efficient tunneling of the transferred hydride through the energy barrier, and underneath the energy maximum for the transition state. It is noted that the evidence to support the existence of a tunnel-ready state for the hydride transfer reactions catalyzed by ADH is ambiguous. We propose that the rate acceleration for ADH is due to the utilization of the binding energy of the cofactor NAD+/NADH in the stabilization of the transition state for enzyme-catalyzed hydride transfer.
对于酶催化氢化物转移所观察到的大幅速率加速的起源，目前尚无共识。对酒精脱氢酶（ADH）催化的氢化物转移反应的最新研究结果的解释集中在这样一种观点上，即有效势垒高度通过量子力学隧穿穿过能垒而降低。这种解释与酶促速率加速是通过直接稳定水中非酶促反应的过渡态这一观点形成鲜明对比。底物磷酸二羟丙酮二价阴离子的结合能为甘油 - 3 - 磷酸脱氢酶（GPDH）催化的氢化物转移反应的过渡态提供了11千卡/摩尔的稳定性。我们总结了证据表明，（GPDH）与二价阴离子激活剂之间的结合相互作用直接用于稳定酶催化氢化物转移的过渡态。考虑了这些二价阴离子结合相互作用用于稳定隧道就绪态（TRS）的可能性，该状态能够使转移的氢化物有效地隧穿能垒，并在过渡态能量最大值之下，但随后又排除了这种可能性。需要指出的是，支持ADH催化的氢化物转移反应存在隧道就绪态的证据并不明确。我们提出，ADH的速率加速是由于利用了辅因子NAD⁺/NADH的结合能来稳定酶催化氢化物转移的过渡态。
