TCA Cycle Regulation

In contrast to glycolysis, which is regulated primarily by PFK-1, the TCA cycle is controlled by the regulation of several enzymes (see Fig. 1). The most important of these regulated enzymes are those that catalyze reactions with highly negative ΔG⁰: citrate synthase, isocitrate dehydrogenase, and the α-ketoglutarate dehydrogenase complex. Reducing equivalents needed for oxidative phosphorylation are generated by the PDHC and the TCA cycle, and both processes are upregulated in response to a decrease in the ATP/ADP ratio.

Figure 1: A. Production of reduced coenzymes, ATP, and carbon dioxide (CO₂) in the tricarboxylic acid cycle. [Note: Guanosine triphosphate (GTP) and ATP are interconverted by nucleoside diphosphate kinase.] B. Inhibitors and activators of the cycle.