Unformatted text preview: ition on second line I Note the position of the “α” in the two new equations! Uncompetitive Inhibition
Inhibitor binds to the enzymesubstrate complex, not to the free enzyme. K’I is the quantity
of interest:
it captures the
inhibition power of
inhibitor I for the
particular reaction
catalyzed. K’i = [ES][I] / [ESI]
(VVP Eq. 1234) Hence:
the SMALLER
the K’i,
the BETTER
the inhibitor! Here:
I
= Uncompetitive Inhibitor
S = Substrate
E = Enzyme
ES = Michaelis complex
ESI = EnzymeSubstrateInhibitor Complex
P = Product Uncompetitive Inhibition
MM equation: v = Vmax[S]/(KM + α‘[S]),
Where α' = (1 + [I]/K'I) and K'I = [ES][I]/[ESI].
LB equation: 1/v0 = (KM /Vmax) (1/ [S]) + α’/ Vmax
VVP 4e Fig 129 LineweaverBurk Plot for Uncompetitive Inhibition: PARALLEL LINES!!
With intersection points 1/v0= α’/Vmax on the vertical axis;
Since Vmax is known, α’ can be calculated;
And from α’, K’I can be calculated using the definition of α’ MichaelisMenten and LineweaverBurk Equations # 3
Uncompetitive Inhibition on last line I I Note the “αprime”s in the last line of the Table!
(αprime = α’ = defined underneath the Table, and also in previous slide) Mixed (noncompetitive) Inhibition
Inhibitor binds to both the enzymesubstrate complex and the free enzyme. Here:
I
= Inhibitor
S = Substrate
E = Enzyme
ES = Michaelis complex
EI = EnzymeInhibitor Complex
ESI = EnzymeSubstrateInhibitor Complex
P = Product Mixed (noncompetitive) Inhibition
VVP 4e Fig 1210 LineweaverBurk Plot for Mixed (noncompetitive) Inhibition:
Remember: No parallel lines, no intersection on point ON yaxis..
No need to remember any equation for a special point or a slope of a line from this slide. MichaelisMenten and LineweaverBurk Equations # 4
Mixed (Noncompetitive) Inhibition on last line I I No need to remember equations from the lowest line inside the Table (about Mixed inhibition) Drug Design
A case study StructureBased Inhibitor Design
of
the enzyme GAPDH
from
the sleeping sickness parasite,
a “Trypanosomatid”. Sleeping Sickness
a.k.a “African trypanosomiasis” Blood stream
form of
parasite Tsetse fly
Lumbar puncture...
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 Fall '08
 HOL
 Biochemistry, Catalysis, Enzyme inhibitor, Lineweaver–Burk plot, Michaelis–Menten kinetics

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