Week 7 Flashcards
What are the structure and function of enzymes?
Globular-acts as boys catalyst
Speed up time for reaction to reach equilibrium
Lower the activation energy of a reaction
What molecules make up catalytic triad?
Serine 195, histidine 57 and asparteate 102
Explain how the catalytic triad acts as a covalent catalysis and acid-base catalysis?
His 57 accepts a proton from Ser 195(acts as a base)
Asp 102 helps orient His 57
Enzymes use one of more of these strategies for catalysis…
Covalent catalysis,General acid-base catalysis,Metal ion catalysis,Catalysis by proximity and orientation of two substrates
Does carbonic anhydrase employs general acid/base catalysis, metal ion catalysis, and catalysis by proximity and orientation of two substrates?
Yes
What does the Zn+ in carbonic anhydrase do?
Zn2+ acts to stabilize the deprotonated form of the water molecule
Why is carbonic anhydrase important in blood?
•Carbon dioxide (CO2) is produced from respiring tissues•CO2 must be transported to the lungs to be exhaled•CO2 is hydrated to carbonic acid in red blood cells•Carbonic acid is a weak acid and dissociates to form bicarbonate ions
Does the action of carbonic anhydrase help buffer blood?
Yes
What is the problem with designing molecules with stronger binding interactions?
Designing molecules with stronger binding interactions results in enzyme inhibitors which block the active site
What is a drug target?
Most drugs act on specific proteins or cells in the body, known as the drug target
What are the main protein drug targets?
Receptors•Enzymes•Transporters•Ion channels
What is reversible inhibition?
Inhibitor bound non-covalently•Prevents substrate from binding •Inhibitor rapidly dissociates from enzyme
What is irreversible inhibition?
Inhibitor bound tightly with enzyme•Slow dissociation of enzyme-inhibitor complex•e.g. nerve gases
What are the 3 types of reversible inhibitors?
Competitive inhibitors•Noncompetitive inhibitors•Uncompetitive inhibitors
What is a competitive inhibitor?
Competitive inhibitors bind to the same site as the enzyme substrate•Hence they compete with the substrate•Chemical structure is therefore similar to the substrate•No reaction takes place on the inhibitor•Inhibition depends on the strength of inhibitor binding and inhibitor concentration
What is a non-competitive inhibitor?
Noncompetitive inhibitors bind to a different site from the enzyme substrate•They are allosteric regulators (stabilize an inactive conformation of the enzyme)•Chemical structure is different from the substrate
Effect is not reversed by adding substrate•Often seen in enzymes at the beginning of a metabolic pathway•Inhibitor tends to be a product further down the pathway that then acts to regulate
Irreversible inhibitors permanently inactivate enzymes•Usually form covalent bonds with the enzyme, that cannot be broken
How does Orlistat act as an irreversible inhibitor?
Orlistat is an anti-obesity drug that inhibits pancreatic lipase•The enzyme is blocked from digesting fats in the intestine•Fatty acids and glycerol are less absorbed as a result•Leads to reduced biosynthesis of fat in the body
How do reversible competitor antagonists work?
Reversible competitive antagonists compete with agonist for binding site on receptors•Hence antagonism can be overcome by adding more agonist•In presence of antagonist, the dose-response curve for an agonist shifts to the right
How do irreversible competitive antagonists work?
Bind at same site as agonist, but irreversibly (cannot be released), usually covalently•Adding more agonist cannot overcome effect•Dose-response curve shifts down
Enzymes as Drug Targets summary
Some enzymes are allosterically regulated by inhibitors or activators•Enzyme inhibitors can be reversible or irreversible•Irreversible inhibitors usually bind covalently to enzymes•Many important drugs are enzyme inhibitors•Reversible competitive antagonists shift the dose-response curve to the right•Irreversible competitive antagonists shift the dose-response curve down
