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Kelath Murali Manoj

Publications and source records attributed to Kelath Murali Manoj.

7 recordsLinked to original sources
arXiv2026

Neuronal electricality founded in murburn-thermodynamic principles: 1. Background and basic theoretical formulation

Trans-membrane ion-gradients and fluxes are central to conventional electrical activity in aerobic cells/organelles. The Murburn concept offers novel physico-chemical models for various metabolic, bioenergetic and electrophysiological phenomena. Here, we develop a foundational framework for neuronal electrical activity and axonal signal propagation using the electron-holding potential (EHP), a dimensionless field related logarithmically to electron chemical potential. By combining local redox relaxation dynamics with spatial transport driven by thermodynamic gradients, we derive a unified reaction-transport-relaxation equation that accounts for resting potential, excitability, waveform generation, and signal propagation within a single formalism. Nonlinear local redox kinetics yield a stable resting state and graded responses from a single scalar field; extending it to the two-variable excitable (FitzHugh Nagumo) form, a bistable reaction with a slow recovery variable, further yields a genuine threshold, all-or-none spikes, a refractory period and a propagating action potential. The framework accommodates known physiological variability of neurons and provides a direct bridge between metabolic/redox state and electrophysiology. This framework offers testable predictions for neuronal dynamics (such as velocity, waveform morphology, and environmental conditions) across biological systems. We derive and solve the equations to obtain the transmembrane potential as a function of time, and the neuronal conduction velocity as a function of parameters like ionic strength, temperature, axon diameter, myelination, and driving potential. In the second part of this work, we present comparative analyses, simulations, and experimental strategies for validation and falsification.

q-bio.NC↗
arXiv2026

Neuronal electricality founded in murburn-thermodynamic principles: 2. Comparisons, evidenced explanations, and predictions

The analyses presented herein demonstrate that neuronal electrical activity can be consistently interpreted as a manifestation of murburn redox-mediated electronic dynamics rather than as a process fundamentally driven by transmembrane ionic flux. By integrating comparison with established models, quantitative predictions, and diverse experimental observations, the murburn framework emerges as a unified and chemically grounded description of excitability. A key strength of the model lies in its predictive structure. Unlike phenomenological frameworks that rely on parameter fitting, the murburn formulation links measurable electrophysiological outputs: such as conduction velocity, waveform morphology, and threshold behavior; to physically interpretable variables including redox kinetics, transport efficiency, and environmental conditions. This enables direct experimental validation through perturbations in oxygen availability, redox balance, solvent properties, ionic strength, and external fields. Importantly, the framework extends beyond neurons to a broader class of excitable systems, including cardiac tissue, photoreceptors, and artificial redox-active materials, suggesting that excitability is a general physicochemical phenomenon rooted in reaction-transport dynamics. While the present work establishes the mid-scale dynamics of neuronal electricality, further developments are required to connect quantum-level electron transfer processes with macroscopic electrophysiological signals such as EEG and EMG. These extensions, along with targeted experimental tests, will determine the ultimate scope and applicability of the murburn paradigm.

q-bio.NC↗
arXiv2018

Murburn scheme for thermogenesis mediated by uncoupling protein

Thermogenesis by uncoupling protein (UCP) has traditionally been explained as the dissipation of proton gradient across the inner mitochondrial membrane into heat. Herein, we propose that UCPs, aided by the large pore and positively charged amino acids of suspended loops, enable protonation and transport of DROS. Thus, UCP facilitates DROS-reactions amongst themselves, forming water and liberating heat around the inner mitochondrial membrane. Thereby, the simple murburn scheme for biothermogenesis integrates structural information of UCP with its attributed physiological function.

q-bio.SC↗
arXiv2018

Unveiling ADP-binding sites and channels in respiratory complexes: Validation of Murburn concept as a holistic explanation for oxidative phosphorylation

Mitochondrial oxidative phosphorylation (mOxPhos) makes ATP, the energy currency of life. Chemiosmosis, a proton centric mechanism, advocates that Complex V harnesses a transmembrane potential (TMP) for ATP synthesis. This perception of cellular respiration requires oxygen to stay tethered at Complex IV (an association inhibited by cyanide) and diffusible reactive oxygen species (DROS) are considered wasteful and toxic products. With new mechanistic insights on heme and flavin enzymes, an oxygen or DROS centric explanation (called murburn concept) was recently proposed for mOxPhos. In the new mechanism, TMP is not directly harnessed, protons are a rate limiting reactant and DROS within matrix serve as the chemical coupling agents that directly link NADH oxidation with ATP synthesis. Herein, we report multiple ADP binding sites and solvent accessible DROS channels in respiratory proteins, which validate the oxygen or DROS centric power generation (ATP synthesis) system in mOxPhos. Since cyanide's heme binding Kd is high (mM), low doses (uM) of cyanide is lethal because cyanide disrupts DROS dynamics in mOxPhos. The critical study also provides comprehensive arguments against Mitchell's and Boyer's explanations and extensive support for murburn concept based holistic perspectives for mOxPhos.

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arXiv2017

Mitochondrial oxidative phosphorylation: Debunking the concepts of electron transport chain, proton pumps, chemiosmosis and rotary ATP synthesis

Herein (the first part of my work), I debunk the long-standing hypotheses that explain mitochondrial oxidative phosphorylation. Simple calculations point out that mitochondria are highly proton-deficient microcosms and therefore, elaborate proton pump machinery are not tenable. Further, other elements like the elaborate electron transport chain, chemiosmosis, rotary ATP synthesis, etc. are also critically evaluated to point out that such complicated systems are non-viable. The communication necessitates a new explanatory paradigm for cellular respiration. In the second part of my work, I have put forward a viable alternative explanatory paradigm for mitochondrial oxidative phosphorylation.

q-bio.BM↗
arXiv2017

Murburn concept: A facile explanation for oxygen-centered cellular respiration

Via a concomitant communication (the first part of my work), I have conclusively debunked the prevailing explanations for mitochondrial oxidative phosphorylation and established the need for a novel rationale to account for the reaction paradigm. Towards the same, murburn concept is hereby floated as a viable explanation (in the second part of my work). It is proposed that the inner mitochondrial membrane (harboring the various metal and flavin enzyme complexes) serves as means to confine and stabilize radical reactions, which effectively couple and bring about ATP synthesis in the proton-deficient microcosm. The proposed scheme is un-ordered and favored by Ockham's razor and evolutionary perspectives. Murburn concept is a paradigm-shift in biochemistry because it advocates that diffusible reactive (oxygen) species are mainstay of routine cellular metabolic process within the mitochondria.

q-bio.SC↗