Modes of Enzymatic Catalysis

1. _________________ modes

A. General _______________ Catalysis

B. __________________ Catalysis

2. ___________________ modes

A. ______________________ Effects

B. __________________________________

1. Chemical Modes of Catalysis

• Reaction acceleration is achieved by catalytic __________________

• A general _______ (B:) can act as a __________________________

• Can remove a proton from water and thereby generate the equivalent of OH- in neutral solution

• Can produce a stronger nucleophilic reactant (X:-)

A. General Acid-Base Catalysis

• A general ________ (BH+) can __________________

• A covalent bond may break more easily if one of its atoms is protonated (below)

B. ________________________ Catalysis

• All or part of a substrate is _________ covalently to the enzyme to form a reactive intermediate

• Can be used for ______________________________

A-X + E X-E + A

X-E + B B-X + E

Example: Sucrose phosphorylase

Step one: a glucosyl residue is transferred to enzyme

Step two: Glucose is donated to phosphate

*(Sucrose is composed of a glucose and a fructose)

2. _________________ of Enzymatic Catalysis

Binding forces utilized for catalysis – ______________________________________________________________________________

1. Charge-charge interactions2. Hydrogen bonds3. Hydrophobic interactions4. Van der Waals forces

A. The Proximity Effect - __________________________ substrate molecules in the active site

(1) Reduces their degrees of freedom

(2) Results in a ___________________________________

(3) The relative _______________________ (“effective molarity”) predicts the rate acceleration expected due to this effect

B. Transition-State (TS) Stabilization transition states bind more tightly than substrates

• The enzyme ____________________, forcing it toward TS

• An enzyme must be complementary to the TS

• Enzymes may bind their transition states _____________ times more tightly than their substrates

Transition-state (TS) __________________

• Stable compounds whose structures resemble _____________ _________________________

• 2-Phosphoglycolate, a TS analog for the enzyme triose phosphate isomerase

• Can be used medically as _______________________________

________________________ Reactions

• Enzyme rates can approach the _____________________ of the rate of diffusion of two molecules in solution

• Under physiological conditions the encounter frequency is about 108 to 109 M-1s-1

• A few enzymes have rate-determining steps that are roughly as fast as the binding of substrates to the enzymes

Triose Phosphate Isomerase (TPI)

Properties of ________________________

• Includes Trypsin, Chymotrypsin,Elastase

• Many digestive proteases similar in ________________ structure

• Chymotrypsin, trypsin and elastase - _______________ structure

• Active site substrate specificities differ due to relatively small differences in __________________________________

Serine Proteases Use Chemical and Binding Modes of Catalysis

______________ (__ amino acids) - ____ ____ ____