8/27 5221 Mechanisms of Receptor Regulation

Competitive inhibitor

Increases Km without changing Vmax

Reversed by increasing substrate concentration [S]

E.g., statins (competitively inhibit HmG CoA reductase)

Uncompetitive inhibitor

Decreases Vmax and Km

Binds to ES complex

Adding more substrate gives the inhibitor more ES complex to bind to and more opportunities to inhibit the enzyme

Difference between uncompetitive inhibitor and competitive inhibitor

Uncompetitive competes for ES, not E

Uncompetitive binds to ES, while competitive binds to E

Mixed inhibitor

Decreases Vmax

Either increases Km (if prefers E) or decreases Km (if prefers ES)

Noncompetitive inhibitor

Decreases Vmax while Km is unchanged

Difference between noncompetitive and competitive inhibitor

Adding more S cannot overcome noncompetitive inhibition

on the other hand, competitive inhibition can be reversed by adding S

Difference between mixed inhibitor and noncompetitive inhibitor

Mixed has different affinity for E vs ES

Noncompetitive has same affinity for E + ES

Homotropic effectors: the substrate itself acts as the allosteric regulator (homotropic)

By one substrate binding, it changes protein structure and makes it easier or harder for other substrates to bind (known as cooperativity)

• Positive cooperativity:

• Negative cooperativity: Binding of a ligand to one site decreases affinity of other sites for ligand

Positive cooperativity

Ligand binding to one site enhances ligand binding to other sites

A ligand binding to the enzyme makes it easier for subsequent ligands to bind

Homologous vs. heterologous desensitization

Homologous: desensitization on the receptor itself (receptor-level; impacts just the receptor)

Heterologous: desensitization on the signaling pathway level (impacts multiple receptors)