How are enzymes regulated?rebecca/153A/W11/Lectures/153A_W11_Lec25_EnzymeRegulation.pdfHow are...
Transcript of How are enzymes regulated?rebecca/153A/W11/Lectures/153A_W11_Lec25_EnzymeRegulation.pdfHow are...
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How are enzymes regulated?
• By controlling their concentration
– Control of synthesis (activation or repression)
– Degradation
• By controlling the availability of substrate
– Production, degradation, compartmentation of
substrate
– Reversible binding of competitive inhibitors
• By controlling the activity of the enzyme
– Reversible binding of modulators/effectors
– Reversible or irreversible covalent modification
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Modulator binding to an allosteric enzyme
influences the shape of the active site
Many allosteric enzymes
have separate subunits
for binding a modulator
(regulatory subunit, R) &
for catalyzing the reaction
(catalytic subunit, C)
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Allosteric enzymes may show sigmoidal
kinetics (positive cooperativity)
Q: Why would sigmoidal
kinetics be beneficial to
an enzyme’s function?
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Modulators may affect the enzyme’s K0.5
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Modulators may affect the enzyme’s Vmax
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An allosteric enzyme catalyzes the first step
of pyrimidine (C, T, U) nucleotide synthesis
(ATCase)
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ATCase is composed of six catalytic and six
regulatory subunits
2 trimers of catalytic subunits (red, blue)
3 dimers of regulatory subunits (yellow)
T-state
R-state
“the regulatory subunits allosterically
reduce the activity of the catalytic
subunits in the intact enzyme”
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ATCase exhibits both homotropic and
heterotropic interactions
Binds regulatory subunits
and stabilizes R-state
Binds regulatory subunits
and stabilizes T-state
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The modulator CTP is a feedback inhibitor
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Binding of the substrates to ATCase induces
a conformational change from T→R
Domains of active site cannot
close because of steric hindrance
from neighboring subunitSubstrate binding promotes separation
of subunits, allowing domain closure
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Enzymes may undergo many different types
of covalent modification (over 500 possible!)
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Reversible phosphorylation is a common
modification for regulating enzyme activity
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Glycogen phosphorylase catalyzes the rate-
controlling step in glycogen breakdown
+ Pi
Glycogen(n-1) +
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Glycogen phosphorylase is a dimer of two
identical subunits
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Glycogen phosphorylase is regulated by
phosphorylation and binding of modulators
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Digestive proteases are regulated through
irreversible covalent modification