Metabolic Pathways A metabolic pathway begins with a

Metabolic Pathways • A metabolic pathway begins with a specific molecule and ends with a product • Each step is catalyzed by a specific enzymeimportance of protein synthesis! Enzyme 2 Enzyme 1 A Reaction 1 Starting molecule © 2011 Pearson Education, Inc. B Reaction 2 Enzyme 3 C Reaction 3 D Product

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) © 2011 Pearson Education, Inc.

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.

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Enzyme Inhibitors Enzyme Unit –Part 2

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 Enzyme Inhibitor

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 © 2011 Pearson Education, Inc.

Figure 8. 17 (a) Normal binding (b) Competitive inhibition Substrate Active site (c) Noncompetitive inhibition Competitive inhibitor Enzyme Noncompetitive inhibitor Allosteric

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

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. O 2 with hemoglobin

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

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 • http: //www. youtube. com/watch? v=PILzv. T 3 sp. CQ

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 βlactam antibiotics act by inhibiting penicillin-binding proteins, which normally catalyze cross-linking of bacterial cell walls.

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 3 D shape of enzyme molecule so active site cannot accept substrate • Can be reversible or irreversible

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

End product inhibition P S E E E I S I E

Enzyme Inhibitors Vioxx and other prescription nonsteroidal antiinflammatory 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 a) b) c) d) competitive inhibitors. noncompetitive inhibitors. allosteric regulators. feedback inhibitors.

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 p. H, enzyme concentration, and substrate concentration on enzyme controlled reactions • Types of enzyme inhibition