Studies on the control of the citric acid cycle in heart
McMinn, Catherine Linda
Since the acceptance of the Citric Acid Cycle as the major route of oxidation in almost all tissues, considerable interest has been focussed on the control of this most fundamental metabolic pathway. This thesis describes studies carried out to investigate the control of the Citric Acid Cycle in heart muscle, using a computer simulation model of the pathway. The simulation technique used was that known as CHEK. This is a program designed for digital computer simulation which is not only rapid and easy to handle, but also allows the simulation of a large number of chemical reactions such as those describing a complex metabolic pathway. The simulation model of the Citric Acid Cycle was constructed by formulating models of each of tne component enzymes of the Cycle from information available in the literature and joining these together. Published values for the concentrations of enzymes, coenzymes and intermediates, and ratios of the various forms of the coenzymes were also used. To assess the control features of the Cyclic enzymes in the simulation studies, the concepts of Sensitivity (control strength) and Elasticity (effector strength) were employed.