focus chapter 8 (kinetic mechanisms and inhibtors)

Question 1

Competitive inhibition

Answer 1

 the inhibitor is structurally similar to the substrate and can bind to the active site preventing the actual substrate from binding
 mimics substrate and competes for the active site

Question 2

uncompetitive inhibition

Answer 2

 the inhibitor binds only to the enzyme-substrate complex
 binds to an allosteric site of the enzyme-substrate complex, causing inactivation

Question 3

noncompetitive inhibition

Answer 3

 the inhibitor binds either the enzyme or enzyme-substrate complex
 binds to an allosteric site of an enzyme-substrate complex, causing inactivation

Question 4

competitive inhibition vmax and km

Answer 4

vmax: unchanged
km: increased

Question 5

non-competitive inhibition vmax and km

Answer 5

vmax: decreased
km: unchanged

Question 6

uncompetitive inhibition vmax and km

Answer 6

vmax: decreased
km: decreased

Question 7

Explain the basis for irreversible enzyme inhibition.

Answer 7

o Interact with the enzyme through covalent attachment
o The modified enzyme is no longer functional

Question 8

List the catalytic triad of amino acids in serine proteases and explain their roles in the enzyme’s mechanism

Answer 8

o Serine, histidine, and aspartic acid
o Histidine removesa proton from serine, generating a highly reactive alkoxide ion
o Alkoxide ion attacks the peptide bond of the substrate
o Aspartate orients the histidine and renders it a better proton acceptor

Question 9

Write out the chemical mechanism (electron movement with arrows) for the serine protease chymotrypsin.

Answer 9

o Substrate binding
o Serine’s nucleophilic attack on the peptide carbonyl group
o Collapse of the tetrahedral intermediate
o Release of the amine component
o Water binding
o Water’s nucleophilic attack on the acyl-enzyme intermediate
o Collapse of the tetrahedral intermediate
o Release of the carboxylic acid component