This preview shows pages 1–3. Sign up to view the full content.
This preview has intentionally blurred sections. Sign up to view the full version.View Full Document
Unformatted text preview: BIOC 460, Spring 2008 LEC 16-17, Enzymes - Regulation 2-3 1 Lectures 16-17 Enzymes: Regulation 2-3 Reversible covalent modification Association with regulatory proteins Irreversible covalent modification/proteolytic cleavage Reading: Berg, Tymoczko & Stryer, 6th ed., Chapter 10, pp. 283-299, Chapter 14, pp. 389-391 Problems: pp. 300-302, Chapter 10: #7, 10, 12, 13 Key Concepts Activities of many key enzymes are regulated in cells, based on metabolic needs/conditions in vivo . Regulation of enzyme activity can increase or decrease substrate binding affinity and/or k cat . 5 ways to regulate protein activity (including enzyme activity): 1. allosteric control 2. multiple forms of enzymes (isozymes) 3. reversible covalent modification-- example: phosphorylation/dephosphorylation phosphorylation ( phosphoryl transfer from ATP to specific -OH group(s) on protein) catalyzed by protein kinases dephosphorylation ( hydrolytic removal of the phosphate groups) catalyzed by protein phosphatases 4. interaction with regulatory proteins examples: protein kinase A (PKA) Ca 2+-calmodulin-dependent kinases 5. irreversible covalent modification, including proteolytic activation (zymogen activation) examples: digestive proteases like chymotrypsin and trypsin blood clotting cascade BIOC 460, Spring 2008 LEC 16-17, Enzymes - Regulation 2-3 2 Learning Objectives Terminology: cAMP, consensus sequence, pseudosubstrate, cascade, reciprocal regulation, zymogen Describe in general terms how cells carry out reversible covalent modification of enzymes, and how the modification would be removed. Name (generic names) the types of enzymes that catalyze phosphorylation and dephosphorylation of proteins, specify what types of amino acid functional groups are generally the targets of phosphorylation, and show the structure of such an enzyme functional group before and after phosphorylation. Explain whether the dephosphorylation reaction is actually the chemical reverse of the phosphorylation reaction, and if not, what type of reaction the dephosphorylation represents. Explain the regulation of protein kinase A (PKA) activity by cAMP, including quaternary structural changes in PKA triggered by cAMP binding. How does the term "pseudosubstrate" relate to the role of the regulatory subunits in PKA? What are the 2 enzymes involved in glycogen metabolism whose activities are reciprocally regulated by phosphorylation/dephosphorylation? Briefly discuss the structure of calmodulin ( Ca 2+ ), including structure of the EF hand motif, and how Ca 2+-calmodulin activates target proteins as an example of how a regulatory protein works....
View Full Document