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The ubiquitous biochemical logic of murburn concept

Kelath Murali Manoj


In peroxidative biotransformations, reactions occurring outside the enzyme`s `active site` were seen to yield selective and specific outcomes. These observations had inspired me then to postulate that `such a non-active site and environment-dependent mechanism could play significant roles in life-sustenance processes, besides the well-established hierarchical molecular control mechanisms at genes` and proteins` levels`. Through the decade that followed, further research on these strings culminated into the formation of murburn concept, a stochastic scheme of electron/moiety transfers and interactions among molecules, unbound ions and radicals present in reaction milieu. The new understanding explained key qualitative and quantitative aspects of heme/flavin enzymology (substrate diversity, reaction stoichiometry, etc.) and electron transfer mechanism in these enzymes` in vitro setups. Further, murburn schemes were proposed to explain xenobiotic metabolism, cellular respiration, bio-thermogenesis and maverick physiological dose-responses. This article deals with a brief summation of the development of murburn concept, its current status and potential implications/applications in biology and medicine.


murburn concept/scheme, ROS, diffusible reactive species, redox metabolism/disease, origin of life, evolution, metabolic logic

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Manoj KM. Chlorinations catalyzed by chloroperoxidase occur via diffusible intermediate (s) and the reaction components play multiple roles in the overall process. Biochim Biophys Acta 2006;1764:1325-1339. doi:10.1016/j. bbapap.2006.05.012.

Manoj KM. The di-flavoenzyme reductase directly activates oxygen for the metabolism of diverse drug molecules by liver microsomal Cytochrome P450s. arXiv preprint q-bio/0610036 2006.

Manoj KM, Hager LP. A colorimetric method for detection and quantification of chlorinating activity of hemeperoxidases. Anal Biochem 2006;348:84-86.

Manoj KM, Hager LP. Chloroperoxidase, a Janus Enzyme. Biochemistry 2008;47:2997-3003. doi:10.1021/ bi7022656.

Manoj KM, Baburaj A, Ephraim B, Pappachan F, Maviliparambathu PP, Vijayan UK, et al. Explaining the atypical reaction profiles of heme enzymes with a novel mechanistic hypothesis and kinetic treat-ment. PLoS One 2010;5:e10601. doi:10.1371/journal. pone.0010601.

Manoj KM, Gade SK, Mathew L. Cytochrome P450 reductase: a harbinger of diffusible reduced oxygen species. PLoS One 2010; 5: e13272. doi:10.1371/journal. pone.0013272.

Andrew D, Hager L, Manoj KM. The intriguing enhancement of chloroperoxidase mediated one-electron oxidations by azide, a known active-site ligand. Biochem Biophys Res Commun 2011;414:646-649. doi:10.1016/j. bbrc.2011.10.128.

Parashar A, Manoj KM. Traces of certain drug molecules can enhance heme-enzyme catalytic outcomes. Biochem Biophys Res Commun 2012;417:1041-1045. doi:10.1016/j.bbrc.2011.12.090.

Gideon DA, Kumari R, Lynn AM, Manoj KM. What is the Functional Role of N-terminal Transmembrane Helices in the Metabolism Mediated by Liver Microsomal Cytochrome P450 and its Reductase? Cell Biochem Biophys 2012; 63: 35-45. doi:10.1007/s12013-012-9339-0.

Gade SK, Bhattacharya S, Manoj KM. Redox active molecules cytochrome c and vitamin C enhance heme-enzyme peroxidations by serving as non-specific agents for redox relay. Biochem Biophys Res Commun 2012;419:211-214. doi:10.1016/j.bbrc.2012.01.149.

Parashar A, Gade SK, Potnuru M, Madhavan N, Manoj KM. The curious case of benzbromarone: insight into super-inhibition of cytochrome P450. PLoS One 2014; 9: e89967. doi:10.1371/journal.pone.0089967.

Parashar A, Venkatachalam A, Gideon DA, Manoj KM. Cyanide does more to inhibit heme enzymes, than merely serving as an active-site ligand. Biochem Biophys Res Commun 2014;455:190-193. doi:10.1016/j. bbrc.2014.10.137.

Venkatachalam A, Parashar A, Manoj KM. Functioning of drug-metabolizing microsomal cytochrome P450s- 1. In silico probing of proteins suggest that the distal heme Ašactive site` pocket plays a relatively Ašpassive role` in some enzyme-substrate interactions. In Silico Pharmacol 2016;4:1. doi:10.1186/s40203-016-0016-7.

Manoj KM, Gade SK, Venkatachalam A, Gideon DA. Electron transfer amongst flavo-and hemo-proteins: diffusible species effect the relay processes, not protein-protein binding. RSC Adv 2016;6:24121-24129. doi: 10.1039/ C5RA26122H.

Manoj KM, Parashar A, Avanthika V, Goyal S, Moharana S, Singh PG, et al. Atypical profiles and modulations of heme-enzymes catalyzed outcomes by low amounts of diverse additives suggest diffusible radicals` obligatory involvement in such redox reactions. Biochimie 2016;125:91-111. doi:10.1016/j.biochi.2016.03.003.

Manoj KM, Parashar A, Gade SK, Venkatachalam A. Functioning of microsomal cytochrome P450s: Murburn concept explains the metabolism of xenobiotics in hepatocytes. Front Pharmacol 2016;7. doi: 10.3389/ fphar.2016.00161.

Manoj KM, Venkatachalam A, Parashar A. Metabolism of xenobiotics by cytochrome P450: novel insights into the thermodynamics, kinetics and roles of redox proteins and diffusible reactive species. Drug Metab Rev 2016;48:41- 42. doi:10.1080/03602532.2016.1191848.

Manoj KM. Debunking chemiosmosis and proposing murburn concept as the explanation for cellular respiration. Biomed Rev 2017; 28: 35-52. doi:10.14748/bmr.v28.4450

Parashar A, Gideon DA, Manoj KM. Murburn concept: A molecular explanation for hormetic and idiosyncratic dose responses. Dose Response. 2018; 16:1559325818774421. doi:10.1177/1559325818774421.

Manoj KM. Aerobic respiration: Criticism of the proton-centric explanation involving rotary ATP synthesis, chemiosmosis principle, proton pumps and electron transport chain. Biochem Insights 2018. doi 10.1177/1178626418818442.

Manoj KM, Parashar A, Jacob VD, Ramasamy S. Aerobic respiration: Proof of concept for the mur-burn perspective. J Biomol Str Dynam 2018. doi: 10.1080/07391102.2018.1552896.

Manoj KM. Murburn scheme for thermogenesis mediated by uncoupling protein. arXiv:1812.06089 [q-bio.SC] 2018. Biomed Rev 2018; 29: xx-xx.

Manoj KM, Hager LP. Utilization of peroxide and its relevance in oxygen insertion reactions catalyzed by chloroperoxidase. Biochim Biophys Acta 2001;1547:408-417. doi: 10.1016/S0167-4838(01)00210-2.

Manoj KM, Yi X, Rai GP & Hager LP. A kinetic epoxidation assay for chloroperoxidase. Biochem Biophys Res Commun 1999;266:301-303. doi:10.1006/bbrc.1999.1810.

Jacob VD, Manoj KM. Are adipocytes and ROS villains, or are they protagonists in the drama of life? The murburn perspective. Adipobiology 2018; 10: xx-xx.



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About The Author

Kelath Murali Manoj
Satyamjayatu: The Science and Ethics Foundation Snehatheeram, Kulappully, Shoranur-2 (PO), Kerala, India

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