Enzyme mechanisms Flashcards
What are mechanisms of enzymes?
-The molecular details of enzyme catalyzed reactions
-Enzyme mechanisms deduced from:
-Protein structural sites
-Enzyme kinetic experiments
-Chemical modification of active site
How do enzymes lower the activation energy of a reaction?
Why is the transition state critical for the conversion of substrates to products?
Describe transition state stabilization
-There is increased interaction of the enzyme with the transition-state
-The enzyme helps distort the substrate geometry (usually these distortion are quite subtle), forcing it toward the transition state
-The active site of the enzyme must be complementary to the transition-state in shape and chemical character, so as to enhance its formation and promote stability
what is the terminology of enzyme mechanisms?
-Reaction mechanism describes the details of a reaction (proton movement, bond breakage, bond formation, etc.) during conversion of substrate to product
-Reactants, products and intermediates are identified
-Enzymatic mechanisms often use some of the same terminology used in organic chemistry, eg. electrophile, nucleophile, etc.
Explain nucleophilic substitution reactions
What amino acids typically participate in the chemistry of catalysis?
why does the enzyme reaction rate generally depend on the pH?
Functionality of amino acids at the active site dictates the pH profile of an enzyme
What is competitive inhibition of an enzyme?
-Inhibitor binds at active site
-Reduces reaction rate
-sequesters enzyme into EI complex
-Hence, there is less free E to bind and engage substrate
What is a suicide inhibitor?
-Essentially “kill” the enzyme by reacting irreversible with a reactive R-group at the active site
-The enzyme is disable permanently and can no longer carry out catalysis
Explain the mechanism of trypsin
Describe how proteinase enzymes cleave peptide bonds on protein substrates (trypsin)
What is the nomenclature for substrate residues of proteinases?
Describe the active site of trypsin prior to catalysis
Explain the first steps in the mechanism of trypsin
Explain the transition state in trypsin
Describe the formation of the acyl-enzyme intermediate from the tetrahedral intermediate in trypsin
What are the final steps in the mechanism of trypsin?
