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Lecture 13

Lecture 13. Regulatory Strategies for Enzymes. Feedback Inhibition. Product acts as an inhibitor of initial enzymatic reaction. Ile inhibits threonine dehydratase. “Sigmoidal” Kinetics. Often regulated enzymes with multiple subunits. Allosteric enzymes. Phosphofructokinase.

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Lecture 13

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  1. Lecture 13 Regulatory Strategies for Enzymes

  2. Feedback Inhibition Product acts as an inhibitor of initial enzymatic reaction. Ile inhibits threonine dehydratase.

  3. “Sigmoidal” Kinetics • Often regulated enzymes with multiple subunits

  4. Allosteric enzymes

  5. Phosphofructokinase • Allosterically inhibited by: • ATP • Citrate • PEP • Allosterically stimulated by: • Fructose 2,6 bisphosphate • AMP, ADP

  6. Regulation by Covalent Modification • Phosphorylation • Tyr, Ser, Thr, His

  7. CH 2 PP i Regulation by Reversible Covalent Modification • Adenylylation • Tyr O Adenine O Enz P ATP O O Enz OH OH

  8. Glycogen Phosphorylase

  9. Glycogen Phosphorylase • Regulatory cascade • Hormonal signal • Allosteric regulation • Glucose and ATP are inhibitors • AMP is activator

  10. Zymogens:Regulation by Proteolytic Cleavage • Trypsinogen, chymotrypsinogen, and procarboxypeptidase are synthesized in pancreas • Activated in intestine by trypsin • Trypsin inhibited by pancreatic trypsin inhibitor

  11. Activation of Chymotrypsin In the intestine:

  12. Activation of Chymotrypsin

  13. Another way to regulate enzymatic reactions Regulate the production of the enzyme. Controlled at thelevel of transcription or translation Modification of mRNA Protein DNA RNA (positive or negative regulation) Controlled by transcription factors.

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