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AbstractThe 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 LD50 (μM lethal concentration) suggests that the classical hemeFe binding-based inhibition rationale is untenable to account for the toxicity of CN. In vitro mechanistic probing of CN-mediated inhibition of hemeFe reductionist systems was explored as a murburn model for mitochondrial oxidative phosphorylation (mOxPhos). The effect of CN in haloperoxidase catalyzed chlorine moiety transfer to small organics was considered as an analogous probe for phosphate group transfer in mOxPhos. Similarly, inclusion of CN in peroxidase-catalase mediated one-electron oxidation of small organics was used to explore electron transfer outcomes in mOxPhos, leading to water formation. The free energy correlations from a Hammett study and IC50/Hill slopes analyses and comparison with ligands $\left( {\text{CO}}/{{{{\text{H}}_{2}}\text{S}}/{\text{N}_{3}^{\text{-}}}\;}\; \right)$ provide insights into the involvement of diffusible radicals and proton-equilibriums, explaining analogous outcomes in mOxPhos chemistry. Further, we demonstrate that superoxide (diffusible reactive oxygen species, DROS) enables in vitro ATP synthesis from ADP+phosphate, and show that this reaction is inhibited by CN. Therefore, practically instantaneous CN ion-radical interactions with DROS in matrix catalytically disrupt mOxPhos, explaining the acute lethal effect of CN.

Prosopis juliflora is a drought-resistant evergreen spiny tree that grows in semi-arid and arid tracts of tropical and sub-tropical regions of the world. Dry pods of P. juliflora are a rich source of carbon (40% total sugar) and nitrogen (15% of total nitrogen) and so can be considered as a good substrate for the microbial growth. The present study was mainly focused on the utilization of these pods for the production and statistical optimization of oxytetracycline (OTC) from Streptomyces rimosus NCIM 2213 under SSF. The spectral characterization and chemical color reactions of purified OTC by UV, FTIR, 1H NMR, 13C NMR, and HPLC revealed that the structure was homologous to a standard sample. A central composite design with 26 trails yielded the following critical values of supplements to be added to the dry pods: maltose (0.125 g/gds), Inoculum size (0.617 mL/gds), CaCO3 (0.0026 g/gds), and moisture content (74.87%) with the maximum OTC yield 5.02 mg/gds.

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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 based on murburn concept was proposed in 2017 (Manoj, 2017). The new proposal is oxygen-centric in essence, and it advocates constructive roles for diffusible reactive oxygen species (DROS) in electron transfer reactions and ATP-synthesis. By the end of 2018, significant arguments and experimental evidences (in vitro, in situ, and in silico) had accumulated supporting the new mechanism. Herein, the authors compare the predictive capabilities of the two models. Theoretical concepts and expectations are detailed to differentiate the two models, and the correlations are cross-checked with the available data/information. Experimental strategies are further charted to delineate and demarcate the two hypotheses’ relevance in mOxPhos.