Factors that Affect the Rates of Enzyme catalyzed Reactions [Enzyme] - ↑ [E], ↑ rate [Enzyme] - ↑ [E], ↑ rate [Substrate]- ↑ [S], ↑ rate only up to a point [Substrate]- ↑ [S], ↑ rate only up to a point pH – optimal range pH – optimal range Temperature- optimal range Temperature- optimal range Inhibitors (↓) or activators ( ↑) Inhibitors (↓) or activators ( ↑)

Effect of increasing substrate concentration on Uncatalyzed rxn rate For UNCATALYZED reactions, as [S] increases, rxn rate increases For UNCATALYZED reactions, as [S] increases, rxn rate increases Rxn rate Rxn rate [ Substrate] [ Substrate] [S] ↑ → ↑ collision rate → ↑ rxn rate [S] ↑ → ↑ collision rate → ↑ rxn rate

Figure 6.15 The catalytic cycle of an enzyme

Enzyme Saturation

At low [S] concentrations, active sites are available; at high [S] are active sites are occupied, rate is limited by availability of enzyme

IB Test Question on lactase 25) How does the enzyme lactase aid the production of lactose- free milk? (IB exam) A) Lactase breaks down lactose, which some people are unable to digest because they do not produce the enzyme in sufficient quantities. B) Lactase catalyzes the synthesis of lactose. C) Lactase stimulates the production of other enzymes that breakdown lactase. D) Lactase allosterically inhibits enzymes that produce lactose.

Figure 6.16 Environmental factors affecting enzyme activity

Effect of Low Temperature Molecules move slowly, % of reactant substrate molecules with enough energy to overcome Ea ↓ Also, enzyme generally needs to be able adjust conformation upon binding of substrate(induced fit); lower KE could impact flexibility of enzyme ↓ catalytic efficiency

Effect of high temperature ↑Temperature → ↑ average KE (energy of motion) of atoms Distance between weakly attracted atoms in side chain ↑ → bonds break

Link to denaturation animation Link to denaturation animation Link to denaturation animation Link to denaturation animation Link to heat denaturation animation Link to heat denaturation animation Link to heat denaturation animation Link to heat denaturation animation

Effect of Changing pH Lower pH → ↑ [H + ] → side chains become more + Higher pH → [H + ] ↓ → side chains become more – Salt bridge and H-bonds disrupted

Figure 6.17 Inhibition of enzyme activity Link to enzyme inhibitors Inhibitor has similar structure to S; binds to active site Inhibitor has different structure to S; binds to allosteric site different from active site. Overcome at high [S]; S outcompetes I at high [S] Not overcome by high [S] Reversible Inhibition: Competitive vs. Noncompetitive

Penicillin as example of competitive inhibitor

Competitive inhibition can be overcome at high concentration of substrate

Non-competitive Inhibition is not overcome at high concentrations of substrate

Which of the following could be a competitive inhibitor of an enzyme given the substrate below?

Effect of [S] on competitive v Noncompetitive inhibitors

Most drugs are enzyme inhibitors: Example: Blood Pressure Lowering medication Link to ACE inhibitors

Figure 6.18 Allosteric regulation of enzyme activity Link to allosteric regulation animation Link to allosteric inhibitor animation

Figure 6.20 Cooperativity Link to hemoglobin

General Pattern for a Metabolic pathway E 1 E 2 E 3 E 4 S I 1 I 2 I 3 P S = substrate P = Product I 1 = Intermediate 1; I 2 = Intermediate 2; I 3 = Intermediate 3 E1 = Enzyme 1; E2 = Enzyme 2; E3 = Enzyme 3; E4 = Enzyme 4; Link to metabolic pathways Link to Lucy Chocolate conveyer belt

Figure 6.19 Feedback inhibition Link to feedback inhibition feedback animation