Murburn precepts for aerobic respiration and homeostasis

Manoj, Kelath Murali; Bazhin, N. M.

doi:10.31219/osf.io/hx4p9

Cited by 25 publications

(93 citation statements)

References 40 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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“…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%

“…We had presented a comparison of 30 point-wise queries and their solutions given by ETC-CRAS and murburn explanations, via an exhaustive invited review (4). Furthermore, we had consolidated the murburn explanation for aerobic respiration by a comparison with the hepatocyte microsomal system (15), accounting for thermogenesis (2), cyanide toxicity (7-9), mitochondrial homeostasis (4,18), explaining overall metabolic purviews (3,6) etc. in diverse journals.…”

Section: On the Critique's Approachmentioning

confidence: 99%

“…Therefore, it was conclusively inferred that the miniscule amount of free protons within a mitochondrion cannot serve the purported proton-pumping proteins, which run to 10 4 -10 5 (4,12,13,15), implying a conservative shortage of ~10 6 free protons in physiological mitochondria. The only way to overcome this predicament is by a hetero-or homo-lysis of matrix water molecules, which requires >79 or >492 kJ/mol respectively (18). That alone would not be adequate, as the trans-membrane shipping incurs a cost of >20 kJ/mol (implying a total cost of ~100 kJ/mol for outward trans-membrane proton pumping).…”

Section: Points Presented For "The Defense Of Chemiosmosis" (1)mentioning

confidence: 99%

“…Further, the 'proton-recycling within a closed mitochondrial pot' purview does not explain the proton deficiency for the chemical reaction of NADH oxidation. This was a charge and mass balancing error that was grossly overlooked in the overall schematics (18). Yet, refusing to see the obvious and elementary flaws, when PJS says that 'water auto-protolysis would afford adequate protons' and 'the energetics of ETC-CRAS is adequate to support proton-pump driven ATP synthesis', it is just a recalcitrant apologist sticking to false claims.…”

Section: Points Presented For "The Defense Of Chemiosmosis" (1)mentioning

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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Critical analysis of explanations for cellular homeostasis and electrophysiology from murburn perspective

Manoj¹,

Tamagawa

2021

Journal Cellular Physiology

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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 associationinduction (or sorption/bulk-phase) hypothesis considers the aqueous phase of dissolved proteins (cytoplasm/protoplasm) as the key determinant of cellular composition and ionic fluxes. In the first school of thought, trans-membrane potential (TMP) and selective ion pumps/channels are deemed as key operative principles. In the latter theory, sorption-desorption dynamics and rearrangements of bulk phase determine the outcomes. In both these schools of thought, theorists believe that the macroscopic phase electroneutrality holds, TMP (whether in resting or in activated state) results solely due to ionic concentration differentials across the membrane, and the concerned proteins undergo major conformation changes to affect/effect the noted outcomes. The new entry into the field, murburn concept, builds starting from molecular considerations to macroscopic observations. It moots "effective charge separation" and intricate "molecule-ion-radical" electron transfer equilibriums as a rationale for ionic concentration differentials and TMP variation. After making an unbiased appraisal of the two classical schools of thought, the review makes a point-wise analysis of some hitherto unresolved observations/considerations and suggests the need to rethink the mechanistic perspectives.

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Murburn precepts for aerobic respiration and homeostasis

Cited by 25 publications

References 40 publications

The murburn precepts for photoreception

The murburn precepts for photoreception

In defense of the murburn explanation for aerobic respiration

Critical analysis of explanations for cellular homeostasis and electrophysiology from murburn perspective

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