Murburn concept: a paradigm shift in cellular metabolism and physiology.

Kelath Murali Manoj

doi:10.1515/bmc-2020-0002

Abstract

Two decades of evidence-based exploratory pursuits in heme-flavin enzymology led to the formulation of a new biological electron/moiety transfer paradigm, called murburn concept. Murburn is a novel literary abstraction from "mured burning" or "mild unrestricted burning". This concept was invoked to explain the longstanding conundrum of maverick physiological dose responses and also applied to remodel the prevailing understanding of drug metabolism and cellular respiration. A conglomeration of simple ideas grounded in the known principles of thermodynamics and reaction chemistry, murburn concept invokes catalytic/functional roles for diffusible reactive species or radicals. Hitherto, diffusible reactive species were primarily seen as toxic agents of chaos, non-conducible to the maintenance of life-order. Since the murburn paradigm offers a distinctly different perspective for several biological phenomena, researchers holding conventional views of cellular metabolism pose a direct conflict of interests to the advancement of murburn concept. Murburn schemes are poised to integrate numerous metabolic motifs with holistic physiological outcomes; redefining pursuits in biology and medicine. To advance this agenda, I present a brief account of murburn concept and point out how redundant ideas are still advocated in some prestigious journals.

Highlights

Two decades of evidence-based exploratory pursuits in heme-flavin enzymology led to the formulation of a new biological electron/moiety transfer paradigm, called murburn concept
We showed that diffusible reactive oxygen species (DROS) could relay electrons between the few/sole CPR and numerous/diverse cytochrome P450 (CYP) [10]
The fact is that Complex V has more than 10 million folds higher affinity for ATP and is a demonstrable ATPase. This reality condemns it to be a physiological ATPase, even though it can have some equilibrium driven ATP synthesis. This simple statement explains all that Dr Nath holds on to or advocates, in support of his ideas! (For the curious ones, the implications of murburn concept can be seen even in the ionic differentials, as I have duly pointed out in my Biochemistry Insights paper by quoting Stoin et al.’s finding, ref. #74 of the same paper.) Besides, we have clearly shown that Complex V driven equilibrium process can only lead to sub-nanomolar to picomolar ranges of ATP, as opposed to the approximately millimolar levels found in mitochondria [26]

Summary

This work is licensed under the Creative Commons

Murburn concept: a paradigm shift in cellular metabolism and physiology of simple quantitative logic, the quintessential tool of science. Imagine a process similar to this, but at a much smaller scale, in a confined (mured- old English) and milder mode without flames, occurring in cellular systems, in which the fuel substrate is brought into “a reactor with catalysts” at suitable concentrations, and oxygen flows in at a steady rate, to dynamically generate more reacted products and less heat. Though a knife may cut the user’s hand (leading to oxidative damage of proteins and lipids), gloves (redox enzymes) and cutting boards (anti-oxidants) and adept handling (steady-state transport) enable one to exploit the knife’s potentials without overt damage to the kitchen/user

Application of murburn concept in ecobiology and medicine

System HPO mXM

HPO mXM mOxPhos

Molecular Explanation for Hormetic and Idiosyncratic Dose