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Murburn concept
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Murburn concept
In the field of enzymology, murburn is a term coined by Kelath Murali Manoj that explains the catalytic mechanism of certain redox-active proteins. The term describes the equilibrium among molecules, unbound ions and radicals, signifying a process of "mild unrestricted redox catalysis".
Murburn is abstracted from "mured burning" (connoting a "closed burning", an oxidative process), and implies equilibriums involving diffusible reactive oxygen species (DRS/DROS/ROS). Though akin to the oxygen assisted combustion of fuel, unlike the flames produced in the open burning process, the biological reaction occurs in enclosed premises, is mild and may generate heat alone (and no flames). Such a reaction could also incur selective and specific electron/moiety transfers.
Further, though burning is a reaction that usually involves oxygen (aerobic process), "burning flames" produced by anoxic oxidants are also well-known. Therefore, the enzymes working via murburn scheme (aerobic or anaerobic) could be called murzymes and the region around the biomolecule where the DRS interacts with the final 'substrate' is called 'murzone'.
While enzyme activities are classically defined by the interaction of the protein with its substrate at a defined active site (necessitating a topological recognition of the interactive participants), murburn scheme obligatorily invokes a DRS (or a reactive radical) for carrying out this agenda. The conventional enzyme-substrate interaction scheme invokes Fischer's lock and key type affinity or Koshland's induced fit theory. That is, a substrate is identified by the enzyme by virtue of a topographical complementation, and thereafter, the enzyme-substrate complex undergoes a "transition-state," leading to products.
Such a system shows certainty/determinism, usually abides by the standard models of kinetics (like Michaelis-Menten scheme) and the inhibitors may be of competitive, non-competitive, uncompetitive, etc. The classical enzymes have a unique substrate or a well defined set of substrates.
In contrast, murburn scheme (as shown in figure) might invoke an enzyme-substrate complementation, but this aspect is not obligatory. The kinetics of the reaction may at times not be traceable with standard models because the diffusible reactive species is subjected to multiple equilibriums and the product of interest may be favorably formed only in discrete concentrations of the protagonists.
Therefore, the outcomes in such systems could be subjected to a lot of uncertainty and the overall reaction scheme might exhibit varying and non-integral stoichiometry. The modulators/influencers (activators or inhibitors) may work by mixed modalities, owing to affects on the protein, substrate or the diffusible species. The murzymes may have a wide variety of substrates, as the reaction scheme is dependent on multiple modalities of interactions and outcomes. These considerations seek us to overcome the aesthetic perspective that DROS are mere manifestations of pathophysiology. A relevant comparison is that the presence of knife-racks, cutting boards and gloves in kitchen (analogous to enzymes like superoxide dismutase and catalase, membrane-embedded proteins with one-electron active redox centers, etc.) does not mean that knife is a dangerous component that must be avoided. On the contrary, it is an important tool across the globe that has to be used with adequate care. Quite similarly, the cellular machinery has evolved to harness the reaction potential of DRS. The aesthetic perspective/concern that DRS would wreak havoc in routine physiology is no more relevant because several decades of research has now clearly established that DRS are routinely observed and unavoidable in physiology, and they cannot be just wished away. It has also been demonstrated that sustained release of DRS could afford selectivity (choice of a particular reactant from a variety, say B from A, B, C and D) and specificity (attack at a specific locus, like alpha- or para- positions of a reactant). Therefore, such a selectivity can be compared to how setting fire to a damp cloth dipped in oil burns the oil first and minimally chars the cloth's fabric. Analogously, murburn activity has cumulative collateral damage, which leads to aging, and ultimately, death. Murburn concept stresses the already well-established fundamental awareness that all molecules/processes in life have spatial, temporal, quantitative and contextual relevance. A comparison of the classical perspectives and murburn concept is given in the figure and the perceptional changes ushered in by murburn concept can be captured in the Table 1.
The new mechanism has been proposed as an explanation for phenomena involving catalytic electron or moiety transfers, chemico-physical changes and unusual observations in various experimental, ecological, metabolic and physiological scenarios. Fundamentally, murburn concept advocates the thesis that DRS are vital requirements for routine metabolic and physiological functions. This theory is validated by its ability to explain the toxicity of cyanide to a variety of important life processes (particularly, respiration and photosynthesis).
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Murburn concept
In the field of enzymology, murburn is a term coined by Kelath Murali Manoj that explains the catalytic mechanism of certain redox-active proteins. The term describes the equilibrium among molecules, unbound ions and radicals, signifying a process of "mild unrestricted redox catalysis".
Murburn is abstracted from "mured burning" (connoting a "closed burning", an oxidative process), and implies equilibriums involving diffusible reactive oxygen species (DRS/DROS/ROS). Though akin to the oxygen assisted combustion of fuel, unlike the flames produced in the open burning process, the biological reaction occurs in enclosed premises, is mild and may generate heat alone (and no flames). Such a reaction could also incur selective and specific electron/moiety transfers.
Further, though burning is a reaction that usually involves oxygen (aerobic process), "burning flames" produced by anoxic oxidants are also well-known. Therefore, the enzymes working via murburn scheme (aerobic or anaerobic) could be called murzymes and the region around the biomolecule where the DRS interacts with the final 'substrate' is called 'murzone'.
While enzyme activities are classically defined by the interaction of the protein with its substrate at a defined active site (necessitating a topological recognition of the interactive participants), murburn scheme obligatorily invokes a DRS (or a reactive radical) for carrying out this agenda. The conventional enzyme-substrate interaction scheme invokes Fischer's lock and key type affinity or Koshland's induced fit theory. That is, a substrate is identified by the enzyme by virtue of a topographical complementation, and thereafter, the enzyme-substrate complex undergoes a "transition-state," leading to products.
Such a system shows certainty/determinism, usually abides by the standard models of kinetics (like Michaelis-Menten scheme) and the inhibitors may be of competitive, non-competitive, uncompetitive, etc. The classical enzymes have a unique substrate or a well defined set of substrates.
In contrast, murburn scheme (as shown in figure) might invoke an enzyme-substrate complementation, but this aspect is not obligatory. The kinetics of the reaction may at times not be traceable with standard models because the diffusible reactive species is subjected to multiple equilibriums and the product of interest may be favorably formed only in discrete concentrations of the protagonists.
Therefore, the outcomes in such systems could be subjected to a lot of uncertainty and the overall reaction scheme might exhibit varying and non-integral stoichiometry. The modulators/influencers (activators or inhibitors) may work by mixed modalities, owing to affects on the protein, substrate or the diffusible species. The murzymes may have a wide variety of substrates, as the reaction scheme is dependent on multiple modalities of interactions and outcomes. These considerations seek us to overcome the aesthetic perspective that DROS are mere manifestations of pathophysiology. A relevant comparison is that the presence of knife-racks, cutting boards and gloves in kitchen (analogous to enzymes like superoxide dismutase and catalase, membrane-embedded proteins with one-electron active redox centers, etc.) does not mean that knife is a dangerous component that must be avoided. On the contrary, it is an important tool across the globe that has to be used with adequate care. Quite similarly, the cellular machinery has evolved to harness the reaction potential of DRS. The aesthetic perspective/concern that DRS would wreak havoc in routine physiology is no more relevant because several decades of research has now clearly established that DRS are routinely observed and unavoidable in physiology, and they cannot be just wished away. It has also been demonstrated that sustained release of DRS could afford selectivity (choice of a particular reactant from a variety, say B from A, B, C and D) and specificity (attack at a specific locus, like alpha- or para- positions of a reactant). Therefore, such a selectivity can be compared to how setting fire to a damp cloth dipped in oil burns the oil first and minimally chars the cloth's fabric. Analogously, murburn activity has cumulative collateral damage, which leads to aging, and ultimately, death. Murburn concept stresses the already well-established fundamental awareness that all molecules/processes in life have spatial, temporal, quantitative and contextual relevance. A comparison of the classical perspectives and murburn concept is given in the figure and the perceptional changes ushered in by murburn concept can be captured in the Table 1.
The new mechanism has been proposed as an explanation for phenomena involving catalytic electron or moiety transfers, chemico-physical changes and unusual observations in various experimental, ecological, metabolic and physiological scenarios. Fundamentally, murburn concept advocates the thesis that DRS are vital requirements for routine metabolic and physiological functions. This theory is validated by its ability to explain the toxicity of cyanide to a variety of important life processes (particularly, respiration and photosynthesis).