Chemiosmotic and murburn explanations for aerobic respiration: Predictive capabilities, structure-function correlations and chemico-physical logic

Manoj, Kelath Murali; Soman, Vidhu; Jacob, Vivian David; Parashar, Abhinav; Gideon, Daniel Andrew; Kumar, Manish; Manekkathodi, Afsal; Ramasamy, Surjith; Pakshirajan, Kannan; Bazhin, N. M.

doi:10.1016/j.abb.2019.108128

Cited by 58 publications

(183 citation statements)

References 88 publications

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“…2. We have traced the historical precedence in literature (16)(17)(18)(19) and also demonstrated the theoretical, experimental and physiological viability of the proposal/fact that DROS (like superoxide) can sponsor non-specific phosphorylations in ambient redox metabolic environments (3,(20)(21)(22)(23)(24). Taking this account in the current context, the murburn model of signal transduction is ratified by the well-known phosphorylation of seven different ser/thr residues on rhodopsin (25,26).…”

Section: Evidence and Arguments Supporting The New Murburn Modelmentioning

confidence: 71%

The murburn precepts for photoreception

Manoj¹,

Jacob²

2020

Biomedical Reviews

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Murburn concept is a redox mechanistic scheme involving interactive equilibriums of discretized or organized protein/substrate 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 thermodynamically and kinetically viable explanations for various physiological/bioenergetic routines like xenobiotic metabolism, unusual dose responses, aerobic respiration, thermogenesis, homeostasis, trans-membrane potential, oxygenic photosynthesis, etc. While proposing the murburn model for photophosphorylation, we had projected that the murburn mechanism could also be relevant for photoreception physiology. Herein, we expand on this aspect and present the basic scheme and evidence in support of the murburn model of photoreception, with retinal/opsin as the salient photon-impingement response-transducing element. In alignment with our earlier murburn schemes, we propose that diffusible reactive oxygen species (DROS, as exemplified by superoxide, which is currently deemed a toxic product of all-trans retinal and NADPH oxidase interactions) is produced in rod/cone cells upon photoactivation and it plays a crucial role in the visual cycle. This is supported by several facts: (i) Layers of photoreceptive neural cells precede the rod/cone cells (with respect to the presentation to oncoming light ray/photon), (ii) There exists high oxygen demand in the retina, (iii) Copious DROS are detected in functional retina, (iv) NAD(P)H/reductase is involved in the cycle, and (v) Events occur at sub-micrometer dimensioned phospholipid disks stacked to stabilize DROS and minimize free protons (quite like the thylakoids that harbor carotenoids in chloroplasts and cyanobacteria). In the new scheme, photo-electric activation leads to charge separation and hyperpolarization in rod/cone cells due to negative charge build-up. This electro-chemical signaling serves as the front-runner to trigger an action potential relay along a neuron and the superoxide mediated phosphorylation of GDP bound to transducin serves as the initiator of signal transduction cascade. The newly proposed scheme allows a simple electrical connectivity of the retina-photoreceptors with the brain via the optic nerve, is anatomically correlated with the structure and resolution of the retina, and is kinetically viable.

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Section: Evidence and Arguments Supporting The New Murburn Modelmentioning

confidence: 71%

The murburn precepts for photoreception

Manoj¹,

Jacob²

2020

Biomedical Reviews

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“…Approximately 2 NADH molecules result in the formation of 5 molecules of ATP and 2 water molecules (2 NADH = 2 H 2 O = 5 ATP → ATP = 0.4 H 2 O from NADH) (51). Approximately 2 molecules of FADH 2 result in the formation of 3 ATP molecules and 2 water molecules (2 FADH 2 = 2 H 2 O = 3 ATP → ATP = 0.66 H 2 O from FADH 2 ) (Manoj et al 2019). Out of the 28 ATP molecules that are generated per 1 glucose molecule through oxidative phosphorylation, approximately 26 ATP molecules will be generated through NADH, and 2 ATP molecules will be generated through FADH 2 .…”

Section: Water Transformations During Oxidative Phosphorylationmentioning

confidence: 99%

Water and Life: The Medium is the Message

et al. 2021

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Water, the most abundant compound on the surface of the Earth and probably in the universe, is the medium of biology, but is much more than that. Water is the most frequent actor in the chemistry of metabolism. Our quantitation here reveals that water accounts for 99.4% of metabolites in Escherichia coli by molar concentration. Between a third and a half of known biochemical reactions involve consumption or production of water. We calculated the chemical flux of water and observed that in the life of a cell, a given water molecule frequently and repeatedly serves as a reaction substrate, intermediate, cofactor, and product. Our results show that as an E. coli cell replicates in the presence of molecular oxygen, an average in vivo water molecule is chemically transformed or is mechanistically involved in catalysis ~ 3.7 times. We conclude that, for biological water, there is no distinction between medium and chemical participant. Chemical transformations of water provide a basis for understanding not only extant biochemistry, but the origins of life. Because the chemistry of water dominates metabolism and also drives biological synthesis and degradation, it seems likely that metabolism co-evolved with biopolymers, which helps to reconcile polymer-first versus metabolism-first theories for the origins of life.

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“…oxidative phosphorylation (mOxPhos) (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Biophysical Chemistry has refused me and my collaborators a platform to present our rebuttals and surprisingly, continues to provide umbrella to the mock 'mOxPhos wars', which is ongoing with another off-shoot of the Mitchell-Boyer paradigm.…”

Section: Manojmentioning

confidence: 99%

“…My collaborator NM Bazhin is a seasoned biophysical chemist, who had also expressed concerns about the chemiosmotic proposal independently (16,17). He subsequently collaborated with me in pulling down the Mitchellian ideas and establishing murburn concept in bioenergetics realms (4,18,19). Several other diverse concerns were reflected in the writings/calls for 'looking beyond the strictures of chemiosmosis'; made by reputed and independent scientists of the past.…”

Section: On the Critique's Approachmentioning

confidence: 99%

“…There is no effort at PJS's end to see that we had comprehensively debunked the "ETC-driven proton pumps generating a proton motive force (pmf; also seen as a trans-membrane potential or TMP), which drives rotary ATP synthesis (RAS)" or "ETC-driven chemiosmotic rotary ATP synthesis (ETC-CRAS)" paradigm. Our effort was commissioned highlighting the multitudes of limitations of individual components and the impossibility of their coming together as a comprehensive whole 'working machine unit' (2)(3)(4)(5)(7)(8)(9)(10)(11)(12)(13)(14)(15). People are entitled to their beliefs but considering the comprehensive treatment I have offered on the subject with my communications, it would take more than what PJS did for anyone to hold on to the ETC-CRAS view now.…”

Section: On the Critique's Approachmentioning

confidence: 99%

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In defense of the murburn explanation for aerobic respiration

Manoj¹

2020

Biomedical Reviews

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The murburn explanation for aerobic respiration was first published at Biomedical Reviews in 2017. Thereafter, via various analytical, theoretical and experimental arguments/evidence published in respected portals over the last three years, my group's works had highlighted the untenable nature of the "electron transport chain (ETC)-driven chemiosmotic rotary ATP synthesis (CRAS)" explicatory paradigm for aerobic respiration. We have also presented strong evidence and arguments supporting the new murburn model of mitochondrial oxidative phosphorylation (mOxPhos). Overlooking the vast majority of our critical dissections, CRAS hypothesis is still advocated by some. Further, queries are posed on the evidence-based murburn explanation without any committed effort to understand the new proposals. Herein, I expose the false attributions made to our works, point out the general and particular flaws/lacunae in the critical attention murburn model received, revisit/dissect the arguments critique(s) floated to support the chemiosmotic proposal, answer the specific queries on murburn explanation and defend/consolidate our proposals for mOxPhos. The current scientific discourse is crucial for correcting major historical errors and finding/founding new concepts of the powering logic and biophysical chemistry of life.

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Chemiosmotic and murburn explanations for aerobic respiration: Predictive capabilities, structure-function correlations and chemico-physical logic

Cited by 58 publications

References 88 publications

The murburn precepts for photoreception

The murburn precepts for photoreception

Water and Life: The Medium is the Message

In defense of the murburn explanation for aerobic respiration

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