Regulatory Properties of the Pyruvate‐Dehydrogenase Complex from Escherichia coli

Abstract

It is shown that the pyruvate‐dehydrogenase complex from Escherichia coli K12 produces, under certain conditions, positive cooperativity for the substrate pyruvate and negative cooperativity for the inhibitor acetyl‐CoA. The target of the two effectors is the pyruvate dehydrogenase component of the complex. Suggestive evidence indicates that pyruvate cooperativity may mostly be of intramolecular nature ( i.e. , occurring within individual pyruvate dehydrogenase molecules) although some interactions between such molecules become apparent in the presence of acetyl‐CoA inhibition. Negative cooperativity exerted by acetyl‐CoA may not be a direct consequence of ligand‐induced conformational changes of or non‐exclusive ligand binding. It was found that a partially inactivated pyruvate dehydrogenase component is activated by acetyl‐CoA rather than inhibited. It has not been possible to demonstrate the occurrence of this activation with the fully active enzyme component; nonetheless, it does not seem unlikely that the negative cooperativity observed is the consequence of acetyl‐CoA both activating and inhibiting (presumably by acting at different sites) pyruvate dehydrogenase catalysis.