PHYSIOLOGICAL FUNCTIONS OF DIFFUSIBLE REACTIVE SPECIES: THE MURBURN PURVIEW

Abstract

Free radicals are generated during routine energy metabolism and cellular respiration. Due to their small molecular size and high reactivity, diffusible radical species (DRS) can freely permeate macromolecular cavities and bring about numerous effects in cellular milieu. A combination of these effects ultimately determines cellular fate and governs the overall physi- ology of organisms. Optimal generation of DRS is necessary for healthy ageing, growth, reproduction and sustenance of life. Diffusible radicals, earlier known to have damaging effects in organisms and form the basis for ageing and disease, are now being hailed as messengers involved in cellular signalling, homeostasis, metabolism, sensory perception, electro- physiology and biological catalysis.

Earlier deemed to be undesirable by-products of cellular respiration, and characterized as toxic agents responsible for oxidative stress-mediat- ed macromolecular damage during oxidative stress-related pathophysiol- ogy, DRS are now considered to be fundamental small molecules which are indispensable for life, mainly because of the murburn purview. Apart from acting on their molecular targets, molecules with redox centers can interact with DRS and lead to variations in DRS-based cellular reactions, and thereby, causing alterations in signal transduction pathways and gene transcription. As a result, cellular metabolism can be altered in pharmacol- ogy and perhaps serve as one of the causes of drug-mediated side-effects. Traditional pharmacological target selection and chemotherapy usually involves binding-based inhibition.

Pharmacological products which contain redox centres are capable of interacting with and reacting with DRS and cause A better understanding of murburn principles can decrease side-effects of pharmaceutical agents and lead to discovery of novel treatment avenues to combat human diseas- es as well as ageing. This minireview focuses on the physiological actions of DRS and their roles from published literature reports and cements the importance of murburn concept in the redox biology of life and in drug discovery.