Sensitivity of Metabolic Fluxes to Covalent Control

This chapter focuses on the sensitivity of metabolic fluxes to covalent control. A major goal in current biological research is to achieve a thorough understanding of the control of metabolic processes. Recent developments suggest that the pathology resulting from chromosomal aneuploidy, oncogene products, and protein overproduction may ultimately be understood in terms of the sensitivity of metabolic processes to control. To obtain a better understanding of the factors controlling the flow through the branch point, many techniques have been developed to measure the rates of carbon flux through the Krebs cycle, the glyoxylate shunt, and ancillary reactions. A key step in the understanding of regulation can be achieved by comparing in vivo fluxes with values calculated from the in vitro constants of the respective enzymes. The partitioning of the flux through the branch point of the Krebs cycle and the glyoxylate shunt is seen to be highly sensitive to control. The control has the interesting feature that the enzyme most affected, the lyase, is not subject to direct control. Instead, on addition of glucose, isocitrate dehydrogenase is directly regulated by dephosphorylation and the rate of production of isocitrate is decreased. As a consequence, the flux through the alternate pathway is drastically reduced, dropping almost to zero.