Electron transfer amongst flavo- and hemo-proteins: diffusible species effect the relay processes, not protein–protein binding

Abstract

Reductase reduces cytochrome c via relays of highly mobile diffusible agents; not by direct binding and inter-protein long-distance electron tunnelling.

Atypical profiles and modulations of heme-enzymes catalyzed outcomes by low amounts of diverse additives suggest diffusible radicals' obligatory involvement in such redox reactions

“…Therefore, they may be called "murzymes" as they are not conventional enzymes that need to bind to their substrates to catalyze them, but they enhance reaction rates by mediating unrestricted redox catalysis around their vicinity. This insight has been further strengthened by the evidence that electron transfers between flavo-and hemo-proteins are also mediated via diffusible reactive species [59]. Therefore, the one-electron peroxidation and twoelectron chlorinations (which is now established to occur via a diffusible radical-mediated process, as was projected earlier [17]) are significantly influenced by redox-active ions and small molecules.…”

Murburn concept explains the acutely lethal effect of cyanide

“…12,13,[31][32][33] This implies that only at higher heme:ligand ratios and high enzyme concentrations, an ion like cyanide serves as an efficient active-site ligand. The in situ or in vitro assays show a low functional IC 50 or pseudo-K i or pseudo-K M (~10 -6 M) for certain enzyme reactions, 12,13,[31][32][33] which cannot be explained by binding-based effects and which captures the essence of physiological toxicities. We have also provided several evidence based arguments that DROS generated in milieu are obligatorily involved and utilized in several heme-enzyme catalyzed specific/selective reactions.…”

“…It was recently proposed that DROS are ultimately and obligatorily required as catalytic agents for metabolic activities and electron transfer (not just as molecular messengers); particularly for ATP-synthesis and heat generation in mitochondria. [3][4][5][6][7]13,32,33 Now, the thought lines that the toxicity difference must primarily lie in the reaction/interaction dynamics with DROS makes better rationale, particularly under the light of the structure-function correlations of mitochondrial proteins. For, the mitochondrial respiratory proteins (Complexes I through IV) show ADP binding sites, O 2 accessible redox centers/channels, and the ability to produce DROS.…”

“…We have repeatedly cautioned that binding-based conventional kinetic/equilibrium constants do not explain reaction outcomes and are not of immense utility in many heme enzyme systems that work via murburn concept. 3,4,12,13,20,21,[32][33][34] This is because the kinetic outcome is a reflection of the diffusible intermediates' reaction with the final substrate. It is in this final step where CN comes to play, wherein it interrupts the DROS-aided synthesis of ATP within the matrix (shown in yellow box).…”

“…We have also shown that DROS-modulating species can have potentially high impact in heme/flavin-enzyme systems' reaction outcomes and that these effects are mediated via one-electron (radical) chemistry. [3][4][5][6][7]12,13,[19][20][21][31][32][33][34][38][39][40][41] The following experiments are suggested to further ratify the proposals/deductions of the current work on the impact of cyanide on cellular respiration and toxicity.…”