Kelath Murali Manoj

• Doctor of Philosophy
• Satyamjayatu: The Science & Ethics Foundation

Research leading to murburn (‘mured burning’) concept disclosed the previously ignored, yet unavoidable central physiological function of diffusible reactive (oxygen/sulfur/nitrogen) species (abbreviated as DRS or DROS/DRSS/DRNS) at low concentrations, namely that of coupling factors in numerous redox-processes, like oxidative-/photo-phosphorylatio...

Thermogenesis, electro-chemical physiology (ECP), and electro-mechanical activities (EMAs) are fundamental facets of cellular functioning that are associated with powering, coherence, homeostasis, sensing, and response to stimuli. The classical Hodgkin–Huxley–Katz purview of ECP is derived from Nernst-based foundations for dilute solutions, whereas...

Bioenergetics is the study of how life-activities are powered within the cell. This also deals with the interactive exchange of matter/radiation between cellular components and their environment, and the accompanying changes thereof. The acclaimed bioenergetics paradigm has relied on “electron transport chains” and selective/stoichiometric electrog...

From Maheswaranathan et al.’s work published in your journal Neuron (July 2023), we note the report of computational modelling of image/signal processing within the retina, advocating a three-layered network that included interneurons and ganglion cells. As seen from globally recognized personas, popular textbooks, timely reviews, and state of the...

The recent paper in Science Advances (May 31, 2023) by Jones et al. revealing the structure of mitochondrial uncoupling protein 1 (UCP1) cannot be interpreted by the chemiosmotic hypothesis. Rather, the murburn model’s projections regarding this protein has been adequately justified by the structure of UCP1. (Disclaimer: This eLetter was communicat...

About 50 years ago, Howard Berg had proposed a ‘rotary motor’ explanatory paradigm for the flagella-assisted motility of bacteria (Berg & Anderson, Nature, 1973), claiming that dispersion of the proton motive force (or pmf, for which Peter Mitchell received the Nobel Prize in 1978) provided the powering in such propulsion (Berg, Annual Review of Bi...

The murburn concept is a novel perspective for understanding cellular function, deeming cells as simple chemical engines (SCE) that are powered by redox reactions initiated by effective charge separation (ECS). The 1-electron active diffusible reactive (oxygen) species, or DR(O)S, equilibriums involved in these processes are also crucial for homeos...

Bioenergetics is the study of how life-activities are powered within the cell. This also deals with the interactive exchange of matter/radiation between cellular components and their environment, and the accompanying changes thereof. The acclaimed bioenergetics paradigm has relied on ‘electron transport chains’ and selective/stoichiometric electrog...

If evolution was/is a fact, a simplified/unifying approach to explain cellular physiology is warranted. Such a perspective should agree with the thermodynamic, kinetic, structural, and operational-probabilistic considerations; without invoking overt intelligence or determinism, and must enable a synthesis from chaos. In this regard, we first list s...

Bacterial flagellar system (BFS) was the primary example of a purported ‘rotary-motor’ functionality in a natural assembly. This mandates the translation of a circular motion of components inside into a linear displacement of the cell body outside, which is supposedly orchestrated with the following features of the BFS: (i) A chemical/electrical di...

Murburn concept constitutes the thesis that diffusible reactive species or DRS are obligatorily involved in routine metabolic and physiological activities. Murzymes are defined as biomolecules/proteins that generate/modulate/sustain/utilize DRS. Murburn posttranslational modifications (PTMs) result because murburn/murzyme functionalism is integral...

As three points are minimally required to define/confine any area, the study of life can be systematized with the following three essential biological principles: (1) Cell theory affords a factual/spatial demarcation of life from non-life, and discretizes/unitizes the organization of complex living beings. (2) Central dogma gives a blueprint for re...

Cyclooxygenase (COX) is a unique membrane-embedded heme-protein that plays pivotal roles in diverse tissues, particularly during inflammation. The protein inserts two molecules of oxygen into the unsaturated fatty acyl species of archidonate and other unsaturated fatty acid substrates. It is known that the protein has two active sites; a tyrosyl-ra...

Murburn concept constitutes the thesis that diffusible reactive species or (DRS) are obligatorily involved in routine metabolic and physiological activities. Murzymes are defined as biomolecules/proteins that generate/modulate/sustain/utilize DRS. Murburn post-translational modifications (PTMs) result because murburn/murzyme functionalism is integr...

If evolution were to be a fact, a simplified and unifying approach to explain cellular physiology is warranted. Such a perspective should agree with the thermodynamic, kinetic, structural and the operational-probabilistic considerations; without invoking overt intelligence or determinism, and must enable a synthesis from chaos. In this regard, we f...

The redox metabolic paradigm of murburn concept advocates that diffusible reactive species (DRS, particularly oxygen-centric radicals) are mainstays of physiology, and not mere pathological manifestations. The murburn purview of cellular function also integrates the essential principles of bioenergetics, thermogenesis, homeostasis, electrophysiolog...

The Z-scheme electron transport chain (ETC) explanation for photosynthesis starts with the serial/sequential transfer of electrons sourced from water molecules bound at Photosystem II via a deterministic array of redox centers (of various stationary/mobile proteins), before \"sinking\" via the reduction of NADP+ bound at flavin-enzyme reductase. Se...

Bacterial flagellar system (BFS) was the first perceived example of a ‘natural rotary-motor” functionality, mandating the translation of a circular motion of components inside into a linear displacement of the cell body outside. This outcome is supposedly orchestrated with the following features of the BFS: (i) A chemical/electrical differential ge...

The redox metabolic and bioenergetic paradigm of murburn concept advocates that diffusible reactive species (DRS, particularly oxygen-centric 1e-active radicals) are a crucial mainstay of physiology, and not mere pathological manifestations. The murburn purview of cellular function also integrates the essential principles of bioenergetics, thermoge...

New techniques and elucidations in structural biology have enabled greater insights into the functioning of proteins. Since its discovery in 1957 by Jens Skou, the membrane protein of Na,K-ATPase (NKA, also known as sodium-potassium pump) has been a focus of intense study, owing to its centrality in neuro-cardio-musculo electrophysiology. Herein, w...

The classical paradigm of visual physiology comprises of the following features: (i) rod/cone cells located at the rear end of the retina serve as the primary transducers of incoming photo‐information, (ii) cis–trans retinal (C20H28O) transformations on rhodopsin act as the transduction switch to generate a transmittable signal, (iii) signal amplif...

The advent of improved structural biology protocols and bioinformatics methodologies have provided paradigm-shifting insights on metabolic or physiological processes catalyzed by homo−/hetero- proteins (super)complexes embedded in phospholipid membranes of cells/organelles. In this panoramic review, we succinctly elucidate the structural features o...

Guo & Rubinstein (25th April, 2022, Nature Communications) continue to interpret their works in bioenergetics using the “Electron Transport Chain – Chemiosmotic (proton motive force, pmf) Rotary ATP Synthesis (or ETC-CRAS)” paradigm, which was conclusively demonstrated to be untenable in recent years.

Oxygenic photosynthesis essentially involves photo-lysis (splitting of water to release oxygen), photo-reduction (formation of NADPH), and photo-phosphorylation (synthesis of ATP) reactions. These reactions use photoactive pigments such as chlorophylls and carotenoids. Z-scheme and Kok-Joliot cycle, the acclaimed and deterministic model of photosyn...

Complex V or FoF1-ATPase is a multimeric protein found in bioenergetic membranes of cells and organelles like mitochondria/chloroplasts. The popular perception on Complex V deems it as a reversible molecular motor, working bi-directionally (breaking or making ATP) via a conformation-change based chemiosmotic rotary ATP synthesis (CRAS) mechanism, d...

The classical paradigm of visual physiology comprises of the following features: (i) rod/cone cells located at the rear end of the retina serve as the primary transducers of incoming photo-information, (ii) cis-trans retinal (C20H28O) transformations on rhodopsin act as the transduction switch to generate a transmittable signal, (iii) signal amplif...

We recently proposed a diffusible reactive (oxygen) species (DRS/DROS) based function for cytochrome b complexes (CBC) and quinones (Q)/quinols (QH2) in the murburn model of bioenergetics. This proposal is in direct conflict with the classical purview of Q-cycle. Via extensive analyses of the structure-function correlations of membrane-quinones/qui...

It is unresolved why lactate is transported to the liver for further utilization within the physiological purview of Cori cycle, when muscles have more lactate dehydrogenase (LDH) than liver. We point out that the answer lies in thermodynamics/equilibriums. While the utilization of NADH for the reduction of pyruvate to lactate can be mediated via t...

Mitochondrial membrane-embedded redox proteins are classically perceived as deterministic ‘electron transport chain’ (ETC) arrays cum proton pumps; and oxygen is seen as an ‘immobile terminal electron acceptor’. This is untenable because: (1) there are little free protons to be pumped out of the matrix; (2) proton pumping would be highly endergonic...

Using in silico docking approaches, we scan the various subunits of Complex V (FoF1ATPase) for putative adenosine nucleotide binding sites. We find that multiple generic ADP/ATP binding sites are present on the alpha-beta binding sites and a conserved ATP binding site is present on the epsilon subunit. These findings support the murburn model of Co...

The heterolytic dissociation of water gives the cation of proton, which has fleeting existence in reality. It exists in aqueous solution in various levels of hydration, as hydronium (H3O+), Zundel (H5O2+) and Eigen (H9O4+) ions. Herein, we present the thermodynamic parameters involved in the overall treatment. These values are crucial in understand...

Pursuits in modern cellular electrophysiology are fraught with disagreements at a fundamental level. While the membrane theory of homeostasis deems the cell membrane and proteins embedded therein as the chief players, the association‐induction (or sorption/bulk‐phase) hypothesis considers the aqueous phase of dissolved proteins (cytoplasm/protoplas...

Bicarbonate ion has been proposed as a potential source for electrons/O-atom in the light reaction of oxygenic photosynthesis, both in the pre-Zscheme era and in recent times. In the light of murburn concept being mooted as a viable explanation for photophosphorylation, we present substantial theoretical analysis which supports the proposal that: (...

Physiological redox conversion of alpha-hydroxy/keto acids is believed to be reversibly carried out by (de)hydrogenases, employing nicotinamide cofactors. With lactate dehydrogenase (LDH) as example, we point out that while the utilization of NADH for the reduction of pyruvate to lactate (the post-glycolytic reaction) can be mediated via the classi...

Starting from the basic molecular structure and redox properties of its components, we build a macroscopic cellular electrophysiological model. We first present a murburn purview that could explain ion distribution in bulk-milieu/membrane-interface and support the origin of trans-membrane potential (TMP) in cells. In particular, the discussion focu...

In this first part of our essay on oxygenic photosynthesis, we address the various aspects of classical and murburn explanations. We had recently pointed out that the classical explanations of- trans-membrane potential (TMP)-based chemiosmotic rotary ATP synthesis, quinone-cycle at cytochrome b6f, chartered electron transport by plastocyanin, and m...

In this second half of our treatise on oxygenic photosynthesis, we provide support for the murburn model of the light reaction of photosynthesis and ratify key predictions made in the first part. Molecular docking and visualization of various ligands of quinones/quinols (and their derivatives) with PSII/Cytochrome b6f complexes did not support char...

Based on murburn model of bioenergetics, we had recently proposed the rationale for cation distribution in cells (Manoj & Tamagawa, 2020) and also demonstrated a potential generation based on murzyme activity (Tamagawa et al., 2021). Herein, the precepts for murburn concept based electrophysiological phenomena- differentiation of ions at the interf...

Murburn concept is a new perspective to metabolism which posits that certain redox enzymes/proteins mediate catalysis outside their active site, via diffusible reactive oxygen species (DROS, usually deemed as toxic wastes). We have recently questioned the proton-centric chemiosmotic rotary ATP synthesis (CRAS) explanation for mitochondrial oxidativ...

The characteristics of the experimentally measured trans-membrane potential (TMP) generated across an artificial membrane intervening two KCl solutions were found to be explicable using simple principles of electrochemistry, as given within the context of Association Induction Hypothesis (AIH). AIH suggests that the heterogeneous ion distribution w...

Blood hemoglobin (Hb), known to transport oxygen, is the most abundant globular protein in humans. Erythrocytes have ∼10⁻³ M concentration of ATP in steady-state and we estimate that this high amounts cannot be formed from 10⁻⁴ − 10⁻⁷ M levels of precursors via substrate-level phosphorylation of glycolysis. To account for this discrepancy, we propo...

We explore the mechanism of electron transfers mediated by cytochrome c, a soluble protein involved in mitochondrial oxidative phosphorylation and cytochrome b5, a microsomal membrane protein acting as a redox aide in xenobiotic metabolism. We found minimal conservation in the sequence and surface amino acid residues of cytochrome c/b5 proteins amo...

Glycolate, lactate, malate, hydroxyglutarate and isocitrate are key alpha-hydroxyacyl metabolic intermediates found in the tissues/cells/organelles of diverse life forms. They are respectively oxidized to glyoxylate, pyruvate, oxaloacetate, ketoglutarate and oxalosuccinate in cell bioenergetic metabolism. These molecules form key junction points fo...

Since 2017, I have argued that affinity/contact-based electron transport chain (ETC) and chemiosmotic rotary ATP synthesis (CRAS) explanation fail to reason the workability or evolution of cellular bioenergetics. Cyanobacteria (Prochlorococcus) can both respire and photosynthesize. In these systems, the aqueous milieu of <0.1 femtoliter (pH 8) cann...

In this manuscript, we we first present a brief review of the structural awareness on chloroplasts, the two photosystems (PS I & PS II, along with the respective light harvesting complexes and chlorophyll binding proteins). Thereafter, with an in silico approach, we attempt to correlate the photoactive proteins’ inhibition by various class of molec...

Quinones are found in the lipid membranes of prokaryotes like E. coli and cyanobacteria, and are also abundant in eukaryotic mitochondria and chloroplasts. They are intricately involved in the reaction mechanism of redox phosphorylations. In the Mitchellian chemiosmotic school of thought, membrane-lodged quinones are perceived as highly mobile conv...

Hemoglobin (Hb) transports oxygen via blood to various cells of the body and it is the most abundant protein found in erythrocytes. Herein, we propose an evidence-based hypothesis that Hb has a hitherto undiscovered function of serving as a murzyme (a redox enzyme working along the principles of murburn concept), catalyzing the synthesis of ATP in...

In normal physiology, living cells are characterized by the interestingly odd disparity in the distribution of monovalent and divalent ions, as per the order: K+ > Na+ > Mg2+ > Ca2+. The ‘in versus out’ ratios of the respective cations can range from a few folds (like that of Mg2+) to a few decades (e.g. Na+ or K+) or even several orders of magnitu...

Aims We aim to demonstrate why deeming diffusible reactive oxygen species (DROS) as toxic wastes does not afford a comprehensive understanding of cytochrome P450 mediated microsomal xenobiotic metabolism (mXM). Background Current pharmacokinetic investigations consider reactive oxygen species formed in microsomal reactions as toxic waste products,...

Murburn concept is a redox mechanistic scheme involving interactive equilibriums of discretized or organized proteins/substrates molecules, unbound ions and radicals (or reactive species); which may afford selective/specific electron transfers, particularly at phospholipid interfaces. Earlier, we have applied murburn concept to provide parsimonious...

The prevailing understanding on the light reaction of oxygenic photosynthesis (photolytic photophosphorylation & NADPH synthesis) considers the vast majority of the diverse pigments, chlorophyll binding proteins (CBPs) and light harvesting complexes (LHCs) as photon-energy relaying facets; only the chlorophyll a couplets at the reaction center of t...

This communication discusses the interactions/outcomes of isoprenoid quinones/quinols (Q/QH2) and membrane-bound cytochromes involved in bioenergetic routines. Particularly, we use qualitative and quantitative arguments to counter the idea that highly deterministic electron relays are triggered within Complex III of mitochondria, resulting from the...

Over the last three years, I had pointed out the untenable nature of the proton-centric ‘chemiosmosis driven rotary ATP-synthesis (CRAS)’ explanation for Oxidative Phosphorylation (OxPhos). Recently, Pedro J. Silva (PJS) [Chemiosmotic misunderstandings (2020). Biophys. Chem. 264, 106424] afforded a part of our work his critical attention, but overl...

In the light reaction of oxygenic photosynthesis, plastocyanin (PC) and ferredoxins (Fd) are small/diffusible redox-active proteins playing key roles in electron transfer/transport phenomena. In the Z-scheme mechanistic purview, they are considered as specific affinity binding-based electron-relay agents, linking the functions of Cytochrome b 6 f (...

Herein, we demonstrate why deeming diffusible reactive oxygen species (DROS) as toxic wastes does not afford a comprehensive understanding of cytochrome P450 mediated microsomal xenobiotic metabolism (mXM). Using the recent insights unveiled in mechanistic redox enzymology, we reason out the remaining pieces of the mXM mechanistic chemistry and sup...

While cytochrome c (Cyt. c) is a soluble protein involved in mitochondrial electron transfer (ET) reactions between Complex III and Complex IV, cytochrome b5 (Cyt. b5) is a microsomal membrane protein acting as a redox aide for diverse cytochrome P450s and their unique reductase. We found little conservation in the sequence and surface amino acid r...

Quinones are found in the lipid-membranes of prokaryotes like E. coli and cyanobacteria, and are also abundant in eukaryotic mitochondria and chloroplasts. They are intricately involved in the reaction mechanism of redox phosphorylations. In the Mitchellian chemiosmotic school of thought, membrane-lodged quinones are perceived as highly mobile conv...

The prevailing understanding on photolytic photophosphorylation, the light reaction of oxygenic photosynthesis, considers the vast majority of the diverse pigments, chlorophyll binding proteins (CBPs) and light harvesting complexes (LHCs) as photon-energy relaying facets; only the two photosystems’ (PS) reaction centers’ chlorophyll a couplets are...

We have recently questioned the long standing explicatory paradigm of Z-scheme of electron transfers leading to the reduction of NADP+, Kok-Joliot cycle of oxygenesis and chemiosmotic rotary ATP synthesis for the physiology of photolysis and photophosphoylation in chloroplasts. Here, we show that the diverse redox enzyme paradigms of xenobiotic met...

Z-scheme is a spatio-temporally demarcated, sequential/serial and vitally deterministic purview of ‘electron transport chain’, purportedly explaining the light reaction of oxygenic photosynthesis. Herein, first, we summarize the salient components of Z-scheme: Kok-Joliot cycle, P680 cycle, Q-cycle, plastocyanin relay, P700 cycle, ferredoxin relay a...

Kok-Joliot cycle is the acclaimed explanation for photolytic oxygen evolution occurring at the MnComplex of Photosystem II of chloroplasts. Herein, in conjunction with my group’s recent critical explorations in this field, an analysis of some pioneers’ datasets is made available. The findings pose significant concerns regarding the four-step linear...

Pursuits in modern cellular physiology are fraught with disagreements on the chemico-physical logic of how a cell coordinates the core aspects of its life-sustaining activities. While the membrane theory of homeostasis deems the cell-membrane and the proteins embedded therein as the chief players, the association-induction (or sorption or bulk-phas...

Within the context of light reaction of photosynthesis, the structure-function correlations of the chloroplast proteins of plastocyanin and ferredoxins (Fd) are analyzed via two perspectives: 1) The Z-scheme, which considers PC/Fd as specific affinity binding-based electron-relay agents, thereby deterministically linking the functions of Cytochrome...

Robert Emerson’s original observation (1957) that “oxygenesis occurs even with far-red light excitation of Photosystem I” is incompatible with the extant Kok-Joliot cycle’s foundation that “photolysis occurs only at red-light stimulated Photosystem II harboring MnComplex”. Further, the Z-scheme of electron transfer cannot account for Emerson’s obse...

The inefficiency of cyanide/HCN (CN) binding with heme proteins (under physiological regimes) is demonstrated with an assessment of thermodynamics, kinetics, and inhibition constants. The acute onset of toxicity and CN’s mg/Kg LD 50 (μM lethal concentration) suggests that the classical hemeFe binding-based inhibition rationale is untenable to accou...

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 phy...

The transformed values of the Gibbs function for a number of radicals are calculated: H, OH, ,SH, NH2, CH3, etc. These data can be used in consideration of the thermodynamics of biochemical reactions involving free radicals.

Queries on aerobic respiration, such as- How is murburn scheme a better explanation for the roles of NADH/oxygen/proton/water, mitochondrial architecture or proteins’ structure/assembly, trans-membrane potential (TMP) and overall reaction rates/scalability? Why is murburn scheme favored on probability and evolutionary logic? How can diffusible reac...

The acclaimed explanation for mitochondrial oxidative phosphorylation (mOxPhos) is a proton or cation centric scheme. Such ideas were recently disclaimed and in lieu, an evidence-based oxygen-centric explanation, murburn concept, was proposed. The new understanding vouches for catalytic roles of diffusible reactive oxygen species (DROS). The involv...

Since mid-1970s, the proton-centric proposal of 'chemiosmosis' became the acclaimed explanation for aerobic respiration. Recently, significant theoretical and experimental evidence were presented for an oxygen-centric 'murburn' mechanism of mitochondrial ATP-synthesis. Herein, we compare the predictive capabilities of the two models with respect to...

Three fundamental queries are addressed on the thermodynamics of aerobic cellular respiration (viz. ATP-synthesis and thermogenesis)- (1) Can the energy of oxygen reduction be utilized for proton transport?, (2) Is the trans-membrane proton differential harness-able as a potential energy capable of doing useful work?, and (3) If the movement of a m...

The long-standing explanation for cellular respiration (mitochondrial oxidative phosphorylation, mOxPhos) in textbooks is proton-centric and involves the elements of Rotary ATP synthesis, Chemiosmosis principle, Proton pumps and Electron transport chain (in short, the RCPE model). Addressing certain lacunae in the RCPE model, an alternative scheme...

Cyanide (CN) is long seen as a binder of heme-Fe centers, disrupting mitochondrial cytochrome oxidase function and oxygen transport by hemoglobin. Recently, a diffusible reactive oxygen species (DROS) mediated reaction mechanism called murburn concept was proposed to explain mitochondrial ATP-synthesis and heat generation. In this purview, CN ion-r...

Cyanide is conventionally perceived as a binder of heme-Fe centers, disrupting oxygen transport by blood hemoglobin and mitochondrial cytochrome oxidase function. This explanation of toxicity would require millimolar (g/Kg dosage) concentration of cyanide, whereas it is lethal even at micromolar (mg/Kg dosage) ranges. It is long known that oxygen c...

The available explanations for oxygenic photosynthesis for the light reaction of photolysis and photophosphorylation (Pl-Pp) are critically analyzed. Based on the structure cum distribution of protagonist molecules and the new mechanistic explanations in redox biochemistry, the interactive dynamics of key reactants are re-assessed for viability. Th...

The acclaimed explanation for mitochondrial oxidative phosphorylation (mOxPhos, or cellular respiration) is a deterministic proton-centric scheme involving four components: Rotary adenosine triphosphate (ATP)-synthesis, Chemiosmosis principle, Proton pumps, and Electron transport chain (abbreviated as RCPE hypothesis). Within this write-up, the RCP...

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-reaction...

The inner mitochondrial membrane protein Complexes (I - V) and prokaryotic respiratory machinery are examined for a deeper understanding of their structure-function correlations and dynamics. In silico analysis of the structure of complexes I-IV, docking studies and erstwhile literature confirm that they carry ADP binding sites which are in close p...

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 dif...

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 “muredburning” or “mildunrestrictedburning” and connotes a novel “molecule-unbound ion–radical” interaction paradigm. Quite unlike the genetic regulations and protein-level affinit...

Supplementary_Information_for_Dose_Response_Mar_2018_revision_Final - Murburn Concept: A Molecular Explanation for Hormetic and Idiosyncratic Dose Responses

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, ch...

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 w...

Using oxygen and NADPH, the redox enzymes cytochrome P450 (CYP) and its reductase (CPR) work in tandem to carry out the phase I metabolism of a vast majority of drugs and xenobiotics. As per the erstwhile understanding of the catalytic cycle, binding of the substrate to CYP's heme distal pocket allows CPR to pump electrons through a CPR-CYP complex...

Background: Peroxidations mediated by heme-enzymes have been traditionally studied under a single-site (heme distal pocket), non-sequential (ping-pong), two-substrates binding scheme of Michaelis-Menten paradigm. We had reported unusual modulations of peroxidase and P450 reaction outcomes and explained it invoking diffusible reactive species [Mano...

Hitherto, electron transfers (ET) between redox proteins are believed to occur via donor-acceptor binding and diffusible reactive species are deemed as deleterious side-products in such systems. Herein, ET from cytochrome P450 reductase (CPR, an animal membrane flavoprotein) and horseradish peroxidase (HRP, a plant hemoprotein) to cytochrome c (Cyt...

Purpose: The currently held mechanistic understanding of microsomal cytochrome P450s (CYPs) seeks that diverse drug molecules bind within the deep-seated distal heme pocket and subsequently react at the heme centre. To explain a bevy of experimental observations and meta-analyses, we indulge a hypothesis that involves a "diffusible radical mediate...