Chapter 7.5 Enzyme Regulation Flashcards
(32 cards)
what is inhibition?
inactivation of enzymatic function
what do enzyme inhibitors usually mimic? (2)
either the transition state or the substrate
what are the 2 types of inhibition?
- irreversible
- reversible
describe irreversible inhibition (2)
- covalent bonding or strong non-covalent bonds
- non-dilutable
describe reversible inhibition (2)
- noncovalent bonds
- dilutable
how does irreversible inhibition work? (2)
- molecules covalently bond to amino acid side chains and the active site is changed to a nonfunctional conformation
- molecules bind to the nonfunctional active site become trapped and disallow substrate binding
give an example of an irreversible protease inhibitor; describe what is blocks how it works (2)
diisopropylfluorophosphate (DFP)
1. blocks protease and phsopholipase enzymes
2. forms a covalent bond with reactive serine residues and renders the enzymes useless
what are the 3 types of reversible inhibition?
- competitive inhibition
- uncompetitive inhibition
- mixed inhibition
how do competitive inhibitors work?
compete with the substrate for the active binding site; if they win they block the acgive site
what happens to competitive inhibitors eventually?
they will eventually dissociate
what does the level of inhibition of competitive inhibitors depend upon? (2)
concentration of both
1. substrate [S] and
2. inhibitor [I]
what competitive inhibitor mimics succinate ligand?
malonate
what is malonate and what does it do?
a competitive inhibitor that competes with the substrate to bind succinate dehydrogenase enzyme
what does competitive inhibition do to Km substrate binding and why?
since higher substrate [S] is needed to reach 1/2 Vmax, Km APPEARS to increase to Km-app and substrate binding appears to be weaker
what may some apo/free enzymes form in the presence of competitive inhibitors?
may form [EI] (enzyme-inhibitor complexes) instead of [ES]
what can overcome the inhibitory effects of competitive inhibitors?
high [S]
do competitive inhibitors alter Vmax?
nope
on reaction velocity plots of competitive inhibition, what happens to Km?
higher Km, closer to origin on LWB plots
what does uncompetitive inhibition do to Km and Vmax?
lowers both!!
describe uncompetitive inhibition (3)
- inhibitor binds away from the active site (NO COMPETE)
- inhibitor binds [ES] complex and alters the active site
- some [S] is wasted since the inhibitor binds [ES] and [S] doesn’t dissociate
what explains what looks like an extra state in uncompetitive inhibition?
it looks like the substrate is bound long, but really the substrate just is not dissociating from the [ESI] complex
describe the slopes on LWB plots with uncompetitive inhibition (also the Vmax and Km)
Km and Vmax are decreased, but the slopes are parallel becayse the overall slope remains the same no matter the level of inhibitor
what does mixed inhibition do to Vmax and Km?
- decreases Vmax
- decreases or increases Km
describe mixed inhibitions (3)
- binds away from the active site
- binds free enzyme or [ES] complex
- causes a conformational change that affects substrate binding (this moves Km up or down)
