1. Metabolic Pathways
A metabolic pathway begins with a specific molecule and ends with a product
Each step is catalyzed by a specific enzyme- importance of protein synthesis!
Enzyme 1
Enzyme 2
Enzyme 3 A B C D
Reaction 1
Reaction 2
Reaction 3
Starting molecule
Product
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2. METABOLISM = Catabolism + Anabolism
Catabolic pathways release energy by breaking down complex molecules into simpler compounds (Cellular respiration, the breakdown of glucose in the presence of oxygen)
Anabolic pathways consume energy to build complex molecules from simpler ones (synthesis of protein from amino acids)
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3. Enzyme Review!
Briefly sketch 3 graphs that show the initial reaction rates of enzyme catalyzed reactions with varying temperature, enzyme concentration, and substrate concentration. Label each graph, and compare the shape of each curve.

5. Enzyme Inhibitors
Enzyme Unit –Part 2

6. Inhibition Active site of enzyme fits perfectly to substrate
However, it is possible for another molecule to bind to an enzymes active site if it is very similar in shape to the enzyme’s substrate
This would inhibit the enzyme’s function
Substrate
Inhibitor
Enzyme

7. Enzyme Inhibitors
Competitive inhibitors bind to the active site of an enzyme, competing with the substrate
Noncompetitive inhibitors bind to another part of an enzyme, causing the enzyme to change shape and making the active site less effective
Examples of inhibitors include toxins, poisons, pesticides, and antibiotics
Cyanide poisoning
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8. (b) Competitive inhibition (c) Noncompetitive inhibition
Figure 8.17
(a) Normal binding
(b) Competitive inhibition
(c) Noncompetitive inhibition
Substrate
Active site
Competitive inhibitor
Enzyme
Figure 8.17 Inhibition of enzyme activity.
Noncompetitive inhibitor
Allosteric 8

9. Competitive inhibition
Usually reversible, because the inhibitor does not permanently bind to the enzyme
Inhibition can be reversed by increasing concentration of substrate

10. Competitive inhibition examples
ACE inhibitors – Block the pathway of hormone, angiotensin II, from constricting blood vessel and increasing blood pressure (Blood vessel dilate)
ACE Inhibition animation
Carbon Monoxide poisoning – CO vs. O2 with hemoglobin

11. Non-competitive inhibition
NON-COMPETITIVE Inhibition does not depend on substrate concentration
Inhibitor will STILL block enzyme function, regardless of low/high concentration of substrate
Two main types
Irreversible inhibition- *could be at ACTIVE SITE!
Allosteric inhibition

12. Irreversible inhibition
Sometimes, inhibitor can remain permanently bonded with the active site and therefore will cause an irreversible block to the substrate
No competition occurs because no matter how much substrate is present (NON-COMPETITIVE) the active sites will be permanently occupied by the inhibitor

13. Non-competitive irreversible inhibition
Penicillin works by permanently occupying the active site of an enzyme that is essential for the synthesis of bacterial cell wall.
Penicillin and other β-lactam antibiotics act by inhibiting penicillin-binding proteins, which normally catalyze cross-linking of bacterial cell walls.

14. Non-competitive allosteric inhibition
If a molecule can bind to another site on the enzyme (besides active site) and stop enzyme function, it is an allosteric inhibitor
Can disrupt the 3D shape of enzyme molecule so active site cannot accept substrate
Can be reversible
or irreversible

15. End-product inhibition
As an enzyme converts substrate to product, it is slowed down because the end product binds to another part of the enzyme and slows down its function
Called negative feedback inhibition
The more product = slower reaction
Controls metabolic processes to stop enzyme from “running wild”
Animation

16. End product inhibitionS P E E S E E I I

17. Enzyme Inhibitors competitive inhibitors. noncompetitive inhibitors.
Vioxx and other prescription nonsteroidal anti-inflammatory drugs (NSAIDs) are potent inhibitors of the cycloxygenase-2 (COX-2) enzyme. High substrate concentrations reduce the efficacy of inhibition by these drugs. These drugs are
competitive inhibitors.
noncompetitive inhibitors.
allosteric regulators.
feedback inhibitors.
Answer: a
This question relates to Concepts 8.4 and 8.5.
Sources
Copeland et al. Mechanism of Selective Inhibition of the Inducible Isoform of Prostaglandin G/H Synthase 1994, PNAS 91:
Chan et al. Rofecoxib [Vioxx, MK-0966; 4-(4'-Methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: A Potent and Orally Active Cyclooxygenase-2 Inhibitor. Pharmacological and Biochemical Profiles 1999, Pharmacology 290: 17

18. Enzyme Quiz on Thurs. 4/9! Concepts to know: Lock and Key hypothesis
Induced fit hypothesis
vocab: substrate, enzyme, active site, activation energy
reaction curves
effects of temperature, and pH, enzyme concentration, and substrate concentration on enzyme controlled reactions
Types of enzyme inhibition