title: Bistability and control for ATP synthase and adenylate cyclase is obtained by the removal of substrate inhibition.
abstract: The thesis of this article is that the raison d'être of the electron transfer chain and the receptor system is to remove 'substrate inhibition' of the enzymes ATP synthase and adenylate cyclase respectively. Activation by energization or hormone is analogous and presents the features of ideal control system; bistability, hysteresis, sensitivity and amplification, and rapid transitions between resting and active states. In the first part of the article, the simplest nontrivial model conforming with the experimental results is put forward. After the system is described, nonlinear and linear models are developed. An important aspect captured by the model is that the enzyme is structurally asymmetric corresponding to the assumption of regulatory site(s) distinct from catalytic site(s). The structural distinction between a regulatory site and a catalytic site entails different binding and specificity properties of the two types of sites with respect to the nucleotides. In the second part, the experimental evidence for the theory is discussed. It is shown that energization and hormone indeed reduce 'substrate inhibition' and that the properties of time lag and criticality predicted by the theory are indeed verified in experiment and are in turn explained by the theory. The theory can explain and correlate various hitherto unexplained experimental phenomena such as the irreversibility of ATP synthesis and the functional role of the ATP synthase asymmetry. The property of hysteresis predicted by the nonlinear model, is indicated by postillumination ATP synthesis, and preactivation of chloroplasts with reduced dithiols indeed display 'hysteresis loops'. In Aplysia memory for short term sensitization may reside in the hysteretic prolonged elevation of cAMP in sensory neurons.
authors.affiliation: Department of Applied Mathematics & Theoretical Physics, University of Cambridge, United Kingdom.
authors.forename: Y
authors.initials: Y
authors.lastname: Schiffmann
mesh_terms: D025181:ATP Synthetase Complexes; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D004579:Electron Transport; D004734:Energy Metabolism; D004789:Enzyme Activation; D004795:Enzyme Stability; D006728:Hormones / Q000502:physiology; D007700:Kinetics; D008433:Mathematics; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D006728:Hormones; D009097:Multienzyme Complexes; D010770:Phosphotransferases; D025181:ATP Synthetase Complexes; D000262:Adenylyl Cyclases