APK 2105C Lecture Notes - Lecture 12: Covalent Bond, Cell Metabolism, Enzyme Inhibitor
23 May 2018
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Chapter 3, Part 5
Cell Metabolism
• Regulation of enzyme activity
o Body regulates enzyme activity to adjust the metabolism in response to changing
demands
o Rather than changing enzyme conc, we use the following mechanisms to
regulate enzyme activity
▪ Allosteric regulation
• Enzymes have active site and regulatory site
• Regulatory site binds to modulator to change the active site or
change catalytic rate of enzyme itself (or both)—makes it unable
to bind to substrate
• Modulator can speed up or slow down enzyme activity
o Speed up = allosteric activation
o Slow down = allosteric inhibition
• Need more substrate to be able to reach same rxn rate that you
would normally have
• Modulators have reversible binding
o When they pop back off, the active site goes back to
normal
• It’s easier for the body to produce more modulators than more
enzymes
▪ Covalent regulation
• To change enzyme activity, must form covalent bond between
chemical group and regulatory site
o Other enzymes catalyze the formation of the covalent bond
• Covalent bonds are strong
o Stays active or inhibited longer than allosteric
• Other enzyme has to come and strip the chemical group off of the
enzyme
• Generally
o Phosphorylation turns things on in cells
▪ Protein kinases phosphorylate things
▪ Add phosphate group (chemical group) to enzymes
o Dephosphorylation turns things off in cells
▪ Phosphatases dephosphorylate things
▪ Take chemical group (maybe a P) off of enzymes
▪ Feedback inhibition (end product inhibition)
• Inhibited enzyme is often the rate-limited enzyme
o Rate-limited enzyme = usually the slowest catalyst in the
bunch of enzymes in the rxn
▪ Can’t go any faster than this enzyme
▪ Usually very early in the metabolic pathway
• Can use intermediates in pathway to allosterically inhibit the
enzymes that produce the products
o Will slow down production of product
• End product inhibition = when you use final product to inhibit
enzymes that make the product
o Type of feedback inhibition
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