Feedback regulation cumulative inhibition

Cumulative Feedback Regulation. In this case, each end product causes a partial inhibition or repression when present in excess alone but all end products must be present to effect complete blockage. The most well known example is the inhibition of glutamine synthetase in E. coli by eight end products (Stadtman, 1966). 

Define the committed step of a metabolic pathway and recognize that it is often the target of feedback regulation. Note the main features of control of branched pathways by feedback inhibition and activation, enzyme multiplicity, and cumulative feedback. 

Most of the pathways of amino acid biosynthesis are regulated by feedback inhibition, in which the committed step is allosterically inhibited by the final product. Branched pathways require extensive interaction among the branches that includes both negative and positive regulation. The regulation of glutamine synthetase from if. coli is a striking demonstration of cumulative feedback inhibition and of control by a cascade of reversible covalent modifications. 

Woolfolk, C. A. Stadtman, E. R. (1967). Regulation of glutamine synthetase III. Cumulative feedback inhibition of glutamine synthetase from Escherichia coli. Arch. Biochem. Biophys. 118,736-755. 

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