THE CATALYTIC ACTIVITIES OF MANY ENZYMES ARE REGULATED The enzvme that catalyzes the first step in a biosynthetic pathway is usul- lly inhibited by the ult imate product( Figure 8-2). The biosynthesis of isoleucine in bacteria illustrates this type of control, which is called feed- back inhibition. Threonine is converted into isoleucine in five steps, the first of which is catalyzed by threonine deaminase. This enzyme is inhib ited when the concentration of isoleucine reaches a sufficiently high level Ways of Enzyme Activity Regulations 1. Feed-back Inhibition 2. Regulatory proteins 3. Covalent modification 4. Proteolytic Activation
1. Feed-back Inhibition 2. Regulatory Proteins 3. Covalent Modification 4. Proteolytic Activation Ways of Enzyme Activity Regulations
1. Feed-back Inhibition Enzyme hibited by Z C D Z End product Figure 8-2 Feedback inhibition of the first enzyme in a pathway by reversible binding of the final product
1. Feed-back Inhibition
Threonine→→→→> Isoleucine Threonine deaminase Isoleucine inhibits by binding to the enzyme at a regulatory site, which is distinct from the catalytic site. This inhibition is mediated by an allosteric interaction which is rapidly reversible. When the level of isoleucine drops sufficiently, threonine deaminase becomes active again, and consequently isoleucine is synthesized once more
Threonine → → → → → Isoleucine Threonine deaminase
coo HaN H-C-OH E B COO HN-C-H H--C-CH, L-Isoleucine igure 8-25 Feedback inhibition. The conversion of L-threonine to L-isoleucine is catalyzed by a sequence of tive enzymes (E to E.). Threonine dehydratase (E )is specifically inhibited by L-isoleucine, the end product of the sequence, but not by any of the four intermediates (A to D), Feedback inhibition is indicated by the dashed feedback line and the o symbol at the threonine dehy dratase reaction arrow, a device that is used throughout this book Lehninger
Lehninger
Binding of a bstrate or signal molecule Transmitted conformational change igure 2-57 Fi Schematic diagram of an allosteric interaction in a protein. The binding of a small molecule or macromolecule to a site in the protein leads to con- formational changes that are propa gated to distant sites