Biochemistry 153A: Week 7 Discussion
Modulation of Enzyme activity

I. Regulation of enzyme catalysis via covalent modification
Irreversible zymogen activation


Initial blood clot formation is mediated by platelets but long-term, wound-healing clotting which follows occurs through a pathway involving approximately 20 different macromolecules. An early step in the long-term clot formation requires activation of the enzyme thrombin from prothrombin. Thrombin then proteolyses fibrinogen to fibrin, which then forms fibers which are a major structural component of clots.
1. Prothrombin is a ___________________.
2. Thrombin is homologous to the family of serine proteases. What proteolysis can be inferred to occur on fibrinogen?
3. Fibrin is a derivative of fibrinogen which is normally present in cells. Explain why fibrin forms clots but fibrinogen does not.
4. Prothrombin contains g-carboxyglutamate (gla) residues that arise from the post-translational conversion of glutamic acids to gla residues. Prothrombin synthesis requires vitamin K. The role of vitamin K can be described as a________________.
5. If an enzyme inhibitor could be the cause for lack of clotting, what type would be most effective and how could it be perfectly designed?

II. Modes of feedback inhibition - Simple, cumulative, and concerted
Controlling product levels via committed steps
Isoenzymes

1) The steady-state concentrations of intermediates in metabolic pathways are near equilibrium for some reactions of the pathway and far from equilibrium for others. True or False.
2) The following represents the biosynthetic pathway for a number of amino acids. Identify the enzymes likely to be regulated by the concentration of each amino acid by drawing an arrow from the endproduct to the enzyme(s) whose activity is likely to be regulated by that endproduct. What types of inhibition are involved at each point of regulation?
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3) Comparing cumulative and concerted feedback inhibition, which would be most effective at preventing unnecessary expenditure of energy and carbon compounds when synthesis of only one pathway product is needed?
4) In opposing pathways, a step that is "irreversible" in the cell can be coordinately regulated because:
a) the concentrations of products are high
b) it is rate-limiting
c) the step in the opposing pathway uses a different reaction catalyzed by a different enzyme
d) the reactants and products are at steady-state

III. Mechanisms of modulation of Allosteric Enzymes
Koshland model is sequential activation
Monod-Wyman-Changeux is all-or-none activation


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