Why is uncompetitive inhibition so rare? A possible explanation, with implications for the design of drugs and pesticides

AbstractUncompetitive inhibition is much less common in nature than consideration of enzyme structure and mechanism might lead one to expect. A possible explanation may be that uncompetitive inhibition of an enzyme in a metabolic pathway can have enormously larger effects on the concentrations of metabolic intermediates than competitive inhibition, under circumstances where their effects on the kinetics of the isolated enzyme are very similar. The severely toxic effects that an uncompetitive inhibitor might be expected to have may have caused enzymes to have evolved in such a way that there has been selection against structures that might favour uncompetitive inhibition.Enzyme kineticsUncompetitive inhibitionCatastrophic responsePesticide desig

Bringing Chemistry to Life: What does it Mean to be Alive?

Abstract The definition of life has excited little interest among molecular biologists during the past half-century, and the enormous development in biology during that time has been largely based on an analytical approach in which all biological entities are studied in terms of their components, the process being extended to greater and greater detail without limit. The benefits of this reductionism are so obvious that they need no discussion, but there have been costs as well, and future advances, for example for creating artificial life or for taking biotechnology beyond the level of tinkering, will need more serious attention to be given to the question of what makes a living organism alive. According to Robert Rosen's theory of (M,R)-systems (metabolismreplacement systems), the central idea missing from molecular biology is that of metabolic circularity, most evident from the obvious but commonly ignored fact that proteins are not given from outside but are products of metabolism, and thus metabolites. Life can be embodied in a mathematical formalism that treats metabolism as a function able to act on an instance of itself to produce a new instance of itself

A Simple Self-Maintaining Metabolic System: Robustness, Autocatalysis, Bistability

International audienceA living organism must not only organize itself from within; it must also maintain its organization in the face of changes in its environment and degradation of its components. We show here that a simple (M,R)-system consisting of three interlocking catalytic cycles, with every catalyst produced by the system itself, can both establish a non-trivial steady state and maintain this despite continuous loss of the catalysts by irreversible degradation. As long as at least one catalyst is present at a sufficient concentration in the initial state, the others can be produced and maintained. The system shows bistability, because if the amount of catalyst in the initial state is insufficient to reach the non-trivial steady state the system collapses to a trivial steady state in which all fluxes are zero. It is also robust, because if one catalyst is catastrophically lost when the system is in steady state it can recreate the same state. There are three elementary flux modes, but none of them is an enzyme-maintaining mode, the entire network being necessary to maintain the two catalysts