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The ETC scheme for the reduction of one oxygen molecule (by the circuit of Complex I/Complex II − 2 Complex III − Complex IV) b .
Source publication
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...
Contexts in source publication
Context 1
... conjunction with the particular issues brought out within each Complex (for example: the limiting rate of anaerobic heme-heme transfer within Complex IV), the realities (as summated above) pose insurmountable constraints on the sequential mode of transfer of four electrons within the ETC. Now, Table 4 captures the gist of overall ETC. As per the prevailing ideas, the reduction of one molecule of oxygen at Complex IV (by a total of four electrons derived from a mole- cule each of NADH and succinate) minimally solicits the syn- chronous and tandem working (or continuous linking) of ~70 proteins/small molecules present on/across the phospholipid membrane. ...
Context 2
... (Table 4), several steps of the proposed ETC would fall short (with respect to probability, thermodynamics, and kinetics; including the long inter-center/overall distances, number of participants and sequential/multi-molecular inter- actions, unfavorable gradients, etc) to explain the sub-millisec- ond oxidation rates experimentally observed in physiological systems. Therefore, it is safe to infer that the proposed outer- sphere sequential ETC cannot afford the overall experimental oxidation rates observed in physiology. ...
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Citations
... This process implicates oxidative reactions, where oxygen acts as the terminal electron acceptor in the electron transport chain [66]. Manoj, (2015) [67] highlighted the crucial role of oxygen in the generation of adenosine triphosphate (ATP), which is an essential molecule that powers the enzymatic reactions required for DHA synthesis. Since DHA is a long-chain fatty acid with twenty-two carbon atoms and six unsaturated bonds, its synthesis process requires more ATP compared to other fatty acids. ...
Biofloc technology (BFT) is an advanced aquaculture method that uses microbial communities to enhance water quality and support aquatic species cultivation. Our research aims to delve into the pivotal role of aeration intensity within BFT systems, revealing its influence on microbial community structures, water quality, and nutrient cycling for L. vannamei culture. Three aeration levels were set with intensities of V75 (75 L/min), V35 (35 L/min), and V10 (10 L/min). The results showed that the lowest aeration intensity (V10) resulted in larger floc sizes and a reduction in the 2D-fractal dimensions, indicating a decreased overall structural complexity of the bioflocs. In addition, water quality parameters, including total ammonia nitrogen and nitrite, remained low across all treatments, highlighting the water-purifying capacity of biofloc. While protein and lipid contents in biofloc did not differ significantly among treatments, docosahexaenoic acid (DHA) levels were highest in the V75 treatment, suggesting that higher aeration promotes the accumulation of essential fatty acids. RDA analysis revealed that microorganisms like Ruegeria sp. and Sulfitobacter mediterraneus negatively correlated with ammonia and nitrite levels, suggesting their key role in converting ammonia to nitrite and nitrate in marine nitrogen cycles. The functional annotation of metagenomes across different aeration levels showed the similarly active roles of microorganisms in nitrogen metabolism and protein synthesis. In conclusion, while variations in aeration intensity affect floc size and the accumulation of essential fatty acids in biofloc, they do not significantly impact overall water quality or core microbial functions in L. vannamei aquaculture. Future research should focus on the effects of aeration strategies on microbial community dynamics and the integration of these data with performance metrics in L. vannamei. These insights can help optimize biofloc cultivation and enhance environmental sustainability in the aquaculture industry.
... Photosynthesis encompasses the process by which photosynthetic units absorb light energy, subsequently transferring it to the reaction center for charge separation and light transformation through the utilization of pigment molecules and other co-factors. High-energy electrons generated in the process create proton gradients in the electron transport chain, which are utilized to synthesize ATP (Manoj, 2018). The transmission of high-energy electrons results in the formation of the essential electron donor NADPH from NADP + . ...
... Recently, the classical explanation for respiration and photosynthesis, the two major modes of cellular powering, as put forth by the Keilin-Mitchell-Boyer (i.e., the traditional perception/ideas of "electron transport chain-chemiosmotic rotary ATP synthesis" or ETC-CRAS) model was demonstrated to be flawed and untenable. 13,14 We had specifically shown that the classical outward proton-pumping explanation was an unviable concept in mitochondria/cyanobacteria because the organelle/organism is practically aprotic; this is something any biochemistry graduate can ascertain! Furthermore, it is untenable that the dissipation of TMP (via return of the "pumped out" protons into the mitochondrial matrix) can lead to an endergonic process of ATP synthesis (via Complex V), on the one hand, and an exergonic heat generation process (via UCP), on the other hand. ...
... In the classical purview advocated by Paul Boyer (Fig. 10, left panel), the multimeric nature of alpha beta monomers in the bulbous F 1 module was taken as a support for proton/electrical-gradient sponsored rotary functionalism of Complex V, which was supposed to enable the phosphoester (anhydride) synthesis from ADP and inorganic phosphate (a chemical reaction) using the binding energy of ATP itself. 35,77 We had pointed out multiple flaws with the "rotary and ATP-synthase" functions of Complex V. 13,15,24,28,[30][31][32][33][34][35][36]78 It is inexplicable how a macroscopic and continuous TMP could be locally tapped by Complex V for rotating the gamma module and catalyzing an endergonic chemical reaction (without the purported incoming protons' direct involvement in the bond formation process). Also overlooked were the lack of protons per se and proton gradient across the respiring prokaryotic cell membrane and mitochondrial inner membrane, the presence of multiple ANBS (adenosine nucleotide binding sites) on both alpha and beta monomers, and the frail asymmetric structure of the complex (wherein one of the alpha-beta dimers is tethered to the membrane via δ-b-a connection), which would not permit free and repeatable rotation. ...
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 cellular milieus are mostly highly packed colloidal coacervates, with various types/levels of macromolecules (ions), interactions, and ordering of water. It has also been established that trans-membrane potential (TMP) manifestation can also be affected by adsorption of ions and effective charge separation (1e processes), necessitating the questioning and expansion of classical purviews. Further, we have demonstrated that the traditional explanation of electrogenic/stoichiometric and vitally deterministic bidirectional pumping/channeling of ions by membrane proteins (such as Na,K-ATPase) as the rationale for resting/dynamic TMP variations is untenable. In stark contrast, the murburn purview of ECP-EMAs acknowledges the complexity and discretization of the organization of water, ions, and macromolecules within the cell and does not solicit selective ion-pumping or TMP-based powering/propagation rationales. Herein, we summarize the murburn rationale for the molecular to macroscopic integration of processes such as thermogenesis, kinetic Na–K differentiation at the cell membrane, visual signal transduction and neuronal impulse relay, Complex V mediated mechano-chemostat function, flagella-based motility, etc., and discuss the alteration of cellular volume/tenor in muscle cell contraction. We assert that the membrane-embedded proteins/enzymes cannot use ATP to work against the natural laws of physics. Therefore, the classical perception of membrane-based ion pumps must be jettisoned to make way for the thermodynamics-friendly murburn purview.
... It requires glucose, adenosine triphosphate (ATP), and NAD+; its products are ATP and H 2 O [50]. Oxidative phosphorylation involves the electron transport chain and chemiosmosis [51]. Electrons travel along the transport chain's components through redox reactions. ...
Highlights
What are the main findings? The constrained disorder principle (CDP) defines systems by their inherent disorder bounded by variable boundaries.
What is the implication of the main finding? The present paper describes the mechanisms of breathing and cellular respiration, focusing on their inherent variability and how the CDP accounts for the variability in breathing and respiration.
The article describes using CDP-based artificial intelligence platforms to augment the respiratory process’s efficiency and treat respiratory diseases.
Abstract
Variability characterizes breathing, cellular respiration, and the underlying quantum effects. Variability serves as a mechanism for coping with changing environments; however, this hypothesis does not explain why many of the variable phenomena of respiration manifest randomness. According to the constrained disorder principle (CDP), living organisms are defined by their inherent disorder bounded by variable boundaries. The present paper describes the mechanisms of breathing and cellular respiration, focusing on their inherent variability. It defines how the CDP accounts for the variability and randomness in breathing and respiration. It also provides a scheme for the potential role of respiration variability in the energy balance in biological systems. The paper describes the option of using CDP-based artificial intelligence platforms to augment the respiratory process’s efficiency, correct malfunctions, and treat disorders associated with the respiratory system.
... Reduced stomatal conductance can further impact photosynthesis and transpiration, limiting plant growth [46,47]. Iron deficiency can disrupt electron transport and ATP synthesis, leading to reduced energy availability for plant growth and photosynthetic processes [48]. By increasing the levels of FeSO4 contents, iron accumulation was also increased. ...
Agricultural production is severely limited by iron deficiency. Alkaline soils increase iron deficiency in rice crops, consequently leading to nutrient deficiencies in humans. Adding iron to rice enhances both its elemental composition and the nutritional value it offers humans through the food chain. The purpose of the current pot experiment was to investigate the impact of Fe treatment in alkaline (pH 7.5) and acidic (pH 5.5) soils to introduce iron-rich rice. Iron was applied to the plants in the soil in the form of an aqueous solution of FeSO 4 with five different concentrations (100, 200, 300, 400, and 500 mM). The results obtained from the current study demonstrated a significant increase in Fe content in Oryza sativa with the application of iron in both alkaline and acidic pH soils. Specifically, Basmati-515, one of the rice cultivars tested, exhibited a notable 13% increase in iron total accumulation per plant and an 11% increase in root-to-shoot ratio in acidic soil. In contrast to Basmati-198, which demonstrated maximum response in alkaline soil, Basmati-515 exhibited notable increases in all parameters, including a 31% increase in dry weight, 16% increase in total chlorophyll content, an 11% increase in CAT (catalase) activity, 7% increase in APX (ascorbate peroxidase) activity, 26% increase in POD (peroxidase) activity, and a remarkable 92% increase in SOD (superoxide dismutase) in acidic soil. In alkaline soil, Basmati-198 exhibited respective decreases of 40% and 39% in MDA and H 2 O 2 content, whereas Basmati-515 demonstrated a more significant decrease of 50% and 67% in MDA and H 2 O 2 in acidic soil. These results emphasize the potential for targeted soil management strategies to improve iron nutrition and address iron deficiency in agricultural systems. By considering soil conditions, it is possible to enhance iron content and promote its availability in alkaline and acidic soils, ultimately contributing to improved crop nutrition and human health.
... To reiterate: given the fact that: (a) NO (nitric oxide, a DROS!) is already recognized as a molecular messenger; (b) the classical bioenergetics paradigm of electron transport chains, proton-pumps and rotary ATP synthesis, etc., are untenable [9]; (c) the DROS-based murburn concept provides a thermodynamically/kinetically and evolutionarily viable explanation for cellular powering [27,44]; and (d) the global and acute toxicity of small doses of cyanide cannot be explained without invoking the murburn concept [14], it is highly opportune to reorient redox biomedical research and clinical therapy efforts for respiratory diseases. It is now imperative to understand the contexts of DR(O)S playing Dr. Jekyll and Mr. Hyde, and to accommodate the murburn perspective. ...
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 homeostasis, coherently networking cells, and rendering electromechanical functions of sensing and responding to stimuli. This perspective presents the true physiological function of oxygen, which is to enable ECS and the generation of DR(O)S. Therefore, DR(O)S must now to be seen as the quintessential elixir of life, although they might have undesired effects (i.e., the traditionally perceived oxidative stress) when present in the wrong amounts, places and times. We also elaborated that tetrameric hemoglobin (Hb) is actually an ATP-synthesizing murzyme (an enzyme working via the murburn concept) and postulated that several post-translational modifications (such as glycation) on Hb could result from murburn activity. The murburn perspective has also enabled the establishment of a facile rationale explaining the sustenance of erythrocytes for 3–4 months, despite their lacking nucleus or mitochondria (to coordinate their various functions and mass-produce ATP, respectively). Although thalassemia has its roots in genetic causation, the new awareness of the mechanistic roles of oxygen-hemoglobin-erythrocyte trio significantly impacts our approaches to interpreting research data and devising therapies for this malady. These insights are also relevant in other clinical manifestations that involve respiratory distress (such as asthma, lung cancer, COVID-19 and pneumonia) and mitochondrial diseases. Herein, these contexts and developments are briefly discussed.
... Keywords: bioenergetics, murburn concept, murzymes, oxidative/photo phosphorylation, trans-membrane potential, proton motive force, electron transport chain, coacervate Layout I. The two major purviews of bioenergetics obligatorily required to carry out key functions (electron/moiety/molecule transfers) in cellular physiology, and some reactions may also occur outside the confines of "active site" (5)(6)(7)(8). ...
... (ii) unusual dose responses, activations and inhibitions (14,(22)(23)(24)(25), (iii) xenobiotic metabolism & drug-drug interactions (12-13, 23, 25-30), (iv) mitochondrial/cellular respiration or oxidative phosphorylation (5)(6)(7)(8)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42), ...
... In this scheme, the roles of components in milieu are also important, as shown for two distinct stochastic routes below: *O2 -+ RH + H + → *R + H2O2 [31.2 kJ/mol] *R + H2O2 → ROH + *OH [-175. 5 --------------------------------------------------------- ------------------------------------------------------RH + H2O2 → ROH + H2O [-244.2 kJ/mol] -------------------------------------------------------The conversion of coumarin to its 3' or 7' hydroxy derivatives can be used to understand that the observe changes in product ratios over time would depend on the dynamics of DRS (which also changes in milieu over the progress of reaction), as a result of thermodynamic and kinetic realities posed in situ (top panel of Figure 9). ...
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 electrogenic ‘ion-pumping’ mediated by vectorial protein-embedded membranes. Therein, an electrochemical gradient was deemed to be the driving force for chemical reactions leading to ATP production, physical thermogenesis by uncoupling proteins, and complex electromechanical processes like information relay along the axon. On one hand, this vitally deterministic perception requires the membrane proteins to “intelligently” manipulate ion-fluxes and generate/harness an electrochemical gradient by a gambit-type logic, and at the other hand, also seeks that the same gradient should cyclically control the membrane-proteins’ activity. Our recent pursuits have questioned such traditional perspectives, and advocated the alternate explanation of murburn concept, leading to a revamping of the macroscopic treatments of overall thermodynamic, kinetic, mechanistic and evolutionary (probability) considerations. The current review aims to consolidate the murburn paradigm of bioenergetics, wherein murzymes initiate redox processes by effective charge separation (ECS) and diffusible reactive species (DRS) formation, enabling cells to work as simple chemical engines (SCE). Herein, we discuss the reaction chemistry of some simple enzyme systems and also delve into protein complex arrays mediated powering routines like mitochondrial respiration-thermogenesis and chloroplast-centered photosynthesis. Further, we remark that the “water-ion-molecules” phase continuum is actually discretized into dynamically fluctuating coacervates, and express concern over the marginalization of sound chemico-physical ideas by the bioenergetics community.
... Later, it was superseded or complemented by the 'proton-binding leading to rotary movement; enabling conformational change' narrative for Complex V (Boyer, 1997). Such perceptions were shown to be unaccountable/untenable and the explanations and bioenergetic phosphorylations in respiration and photosynthesis were thoroughly overhauled by the paradigm-shifting insights of murburn concept (Manoj, 2018a(Manoj, , 2018b(Manoj, , 2018c(Manoj, , 2020a(Manoj, , 2020b(Manoj, , 2020cManoj & Bazhin, 2021a;, Manoj, Soman, et al., 2019, Manoj & Bazhin, 2021b, Manoj, Jacob, et al. 2021, Manoj et al., 2022a, 2022b. Murburn perspective posits that diffusible reactive species (DRS, generated in cellular redox reactions, erstwhile considered as toxic waste products!) are crucial for explaining the respiratory and photosynthetic physiology. ...
... Murburn concept (Manoj 2018c) indentifies that the chemical reaction (not pumping activity) of respiratory 1electron donor redox centres with O 2 at the inner surface of the inner mitochondrial membrane produces O 2 Ãradicals, which (i) modulate TMP, (ii) attack P i and ADP forming P i à and ADP à radicals, which in an exergonic way produce ATP in fluid, and (iii) attract protons which are used in some radical reactions, whereby (iv) complex V regulates proton flux and in this way helps controlling radical chemistry. Via these works, Mitchellian pmf was shown to be untenable in mitochondria (Manoj, 2018b). Complex V (also known as F o F 1 ATPase), another example known of a rotary bimolecular system, was elucidated to work via much simpler 'murburn' principles . ...
... 7. Also, when the energetics could not be accounted with a proton-based differential, an electrical component (whose source was unknown!) was added to the chemical term. This is neither proper thermodynamic accounting nor is there any scientific consensus/agreement in the values determined with such ideas/procedures (Manoj, 2018b(Manoj, , 2020c, Manoj, Soman, et al., 2019)! Such consideration is equivalent to a banking process where one withdraws a sum of 20$from one's checking account, only to have the bank miraculously responding by depositing 120$into the savings account! ...
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 differential generates proton motive force (pmf, including a trans-membrane potential, TMP), which is electro-mechanically transduced by inward movement of protons via BFS. (ii) Membrane-bound proteins of BFS serve as stators and the slender filament acts as an external propeller, culminating into a hook-rod that pierces the membrane to connect to a ‘broader assembly of deterministically movable rotor’. We had disclaimed the purported pmf/TMP-based respiratory/photosynthetic physiology involving Complex V, which was also perceived as a ‘rotary machine’ earlier. We pointed out that the murburn redox logic was operative therein. We pursue the following similar perspectives in BFS-context: (i) Low probability for the evolutionary attainment of an ordered/synchronized teaming of about two dozen types of proteins (assembled across five-seven distinct phases) towards the singular agendum of rotary motility. (ii) Vital redox activity (not the gambit of pmf/TMP!) powers the molecular and macroscopic activities of cells, including flagella. (iii) Flagellar movement is noted even in ambiances lacking/countering the directionality mandates sought by pmf/TMP. (iv) Structural features of BFS lack component(s) capable of harnessing/achieving pmf/TMP and functional rotation. A viable murburn model for conversion of molecular/biochemical activity into macroscopic/mechanical outcomes is proposed herein for understanding BFS-assisted motility.
• HIGHLIGHTS
• The motor-like functionalism of bacterial flagellar system (BFS) is analyzed
• Proton/Ion-differential based powering of BFS is unviable in bacteria
• Uncouplers-sponsored effects were misinterpreted, resulting in a detour in BFS research
• These findings mandate new explanation for nano-bio-mechanical movements in BFS
• A minimalist murburn model for the bacterial flagella-aided movement is proposed
Communicated by Ramaswamy H. Sarma
... The electron transport chain located at the inner surface of the mitochondrial membrane is mainly involved in the synthesis of ATP (Letts and Sazanov, 2017). The respiratory chain located at the inner mitochondrial surface is composed of four different protein complexes, and free energy is generated by the pumping of protons Structural Functional Characterization of Cytochrome b in bc 1 and b 6 f Complexes across the membrane and by the transferring of electrons between the complexes (Manoj, 2018). This free energy is used for the generation of electrochemical gradients, across the mitochondrial membrane. ...
Mitochondrial cytochrome b (cyt b) transfers the electrons in bc1 complex from ubiquinone to cytochrome
c reductase in the mitochondrial respiratory chain, and similarly in b6f enzyme complex, from plastoquinol
(QH2) to plastocyanin (Pc) within the thylakoid membrane. Mitochondrial cyt b in bc1 complexes contains
eight transmembrane helices A to H; two of these, B and E along with two histidines, are cross-linked
with two hemes located at the top and bottom of the membrane. The b6f complex contains four large
subunits which include cytochrome f, b, Rieske iron-sulfur protein, and subunit IV. Electrons transferred
through these complexes are responsible for the pumping of protons across the membrane to produce
ATP through ATP synthase. The present review provides the structural comparison of mitochondrial cyt
b in ten model organisms targeting archaea, prokaryotes, and eukaryotes, highlighting phylogenetic and
mutational analysis. Polymorphism in the mitochondrial cyt b gene helps in studying the biodiversity and
is a valuable tool for the identification of species. Mutations in the cyt b gene produce abnormal protein
leading to deficiencies in the complex III (coenzyme Q), resulting in defective oxidative phosphorylation
and consequently effects other metabolic pathways. In the present article, we comprehensively compare
the biodiversity of cyt b in bc1 and b6f complexes using in silico structural analysis tools, emphasizing that
despite vast knowledge available in this field, still there are so much to explore about cyt b
... After this, Paul Boyer (1964, and several publications thereafter until the next ten years) made a volte-face and floated the "conformation-change coupling" model in which reduction of proteins (particularly, involving the thiol groups) by electron-transfer processes changed their conformations, which in turn enabled ATP synthesis. While several of Mitchell's ideas like proton motive force/chemiosmosis and Q-cycle have been debunked (Manoj, 2017(Manoj, ,2018aManoj et al., 2020b;Manoj et al., 2022d), the vectorial nature of cell/organelle membrane remains valid even today. In the mid-1970s, after Howard Berg's purported discovery of "rotary function" in bacterial flagellar basal module and after Mitchell's ideas gathered traction with the community, Boyer found it opportune to make several major shifts, yet again. ...
... With reference to mitochondrial oxidative phosphorylation, this proposal vouches that some of the 'electron transport chain' (ETC) proteins (Complexes I, III & IV) serve as proton pumps, leading to the establishment of 'proton motive force' (pmf) consisting of a chemical pH gradient and an electrical trans-membrane potential (TMP), which in turn, enables 'chemiosmotic rotary ATP synthesis' (CRAS) by Complex V. We had provided elaborate critique of the pmf-based explanation for bioenergetics (Manoj, 2017;Manoj, 2018a) and proposed an idea in lieu called murburn concept. The insights derived from murburn concept were applied to explain the observations in various core physiologies involving oxygen (Manoj et al., 2022a CBI;Manoj & Gideon, 2022), such as: xenobiotic metabolism and anomalous dose responses (Manoj et al., 2016a;Parashar et al., 2018;, aerobic respiration, thermogenesis and homeostasis Manoj et al., 2019a,b;Manoj et al., 2020a;Manoj & Bazhin, 2021, Manoj et al., 2022b, photo-transduction in vision (Manoj & Jacob, 2020, Manoj et al., 2022c, oxygenic photosynthesis (Gideon et al., 2020;Manoj et al., 2020b;Manoj & Manekkathodi, 2021;Manoj et al., 2021a,b;Manoj et al., 2022d-f), ionic differentials and electrophysiology (Manoj & Tamagawa, 2021;Manoj et al., 2021c;Manoj et al., 2022c,h), etc. ...
... Our critical publications in recent times and the citations therein (Manoj, 2018a;Manoj et al., 2019a-b;Manoj, 2020a-b;Manoj et al., 2020a-b;Manoj & Bazhin, 2021;Manoj et al., 2022e) have brought to the fore that: (i) As pointed out in the authentic biography of Peter Mitchell and elsewhere (Prebble, 2000;Prebble & Weber, 2003;Roskoski 2004) Very importantly, the ETCs and proton pumps working logic is compared in the right panel of Figure 2. As seen, the Mitchellian proposals violate fundamental concepts of electrochemistry and feasibility for getting a working/workable chemical system. There is no evidence to say that the ETCs of the two anti-parallel metabolic schemes are arranged distinctly or separately in the cyanobacterial thylakoid membranes, in the necessary sequence and orientations. ...
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 first list salient theories in cellular physiology for: (i) powering (generation of chemical/heat energy), (ii) coherence (interconnectivity and workability as a unit), (iii) homeostasis (metabolizing and expelling of unfamiliar/unwanted materials, maintaining concentration/volume), and (iv) cellular electrical-mechanical activities. While doing so, we discuss the scopes and limitations of: (a) the classical active-site affinity and recognition-based modality of lock-key and induced-fit enzyme-catalytic mechanisms established by Fisher/Koshland, (b) membrane-pump hypothesis acclaimed by biologists-physicians and historically championed by the British Nobel-laureates like Hodgkin-Huxley-Katz-Mitchell, and (c) association-induction hypothesis advocated by notable physicists-physiologists from various parts of the world, e.g. Gilbert Ling (China-USA), Gerald Pollack (USA), Ludwig Edelmann (Germany), Vladimir Matveev (Russia), Hirohisa Tamagawa (Japan), etc.]. We apply murburn concept (the thesis that diffusible reactive species play vital roles in maintaining life-order) to amalgamate several core cellular functions and further discuss the prospects for establishing the continuum of the principles of physics in biology.
