Parashar Abhinav, Gideon Daniel Andrew, Manoj Kelath Murali
Department of Biotechnology, Vignan's University, Vadlamudi, Guntur, Andhra Pradesh, India.
CIDR-MCBL, Indian Institute of Science, Bengaluru, Karnataka, India.
Dose Response. 2018 May 9;16(2):1559325818774421. doi: 10.1177/1559325818774421. eCollection 2018 Apr-Jun.
Recently, electron transfers and catalyses in a bevy of redox reactions mediated by hemeproteins were explained by murburn concept. The term "murburn" is abstracted from "" or "" and connotes a novel "" interaction paradigm. Quite unlike the genetic regulations and protein-level affinity-based controls that govern order and specificity/selectivity in conventional treatments, murburn concept is based on stochastic/thermodynamic regulatory principles. The novel insight necessitates a "reactivity outside the active-site" perspective, because select redox enzymatic activity is obligatorily mediated via diffusible radical/species. Herein, reactions employing key hemeproteins (as exemplified by CYP2E1) establish direct experimental connection between "additive-influenced redox catalysis" and "unusual dose responses" in reductionist and physiological milieu. Thus, direct and conclusive molecular-level experimental evidence is presented, supporting the mechanistic relevance of murburn concept in "maverick" concentration-based effects brought about by additives. Therefore, murburn concept could potentially explain several physiological hormetic and idiosyncratic dose responses.
最近，血红素蛋白介导的一系列氧化还原反应中的电子转移和催化作用已通过murburn概念得到解释。术语“murburn”是从“”或“”中抽象出来的，意味着一种新颖的“”相互作用范式。与传统治疗中控制秩序和特异性/选择性的基因调控和基于蛋白质水平亲和力的控制截然不同，murburn概念基于随机/热力学调控原则。这种新颖的见解需要一个“活性位点之外的反应性”视角，因为特定的氧化还原酶活性必然是通过可扩散的自由基/物质介导的。在此，使用关键血红素蛋白（以CYP2E1为例）的反应在还原论和生理环境中建立了“添加剂影响的氧化还原催化”与“异常剂量反应”之间的直接实验联系。因此，提供了直接且确凿的分子水平实验证据，支持murburn概念在添加剂引起的基于“异常”浓度效应中的机制相关性。所以，murburn概念有可能解释几种生理兴奋效应和特异剂量反应。
