Transcript No Slide Title

Bio 98 - Leture 8
Enzymes I
Enzymes
1. Selective catalysis and regulation of metabolic rxns
- enzymes are unchanged by the reaction
- some require co-factors (small organic molecules
&/or metals such as Ca, Zn, Cu or Fe, or heme)
2. Most are proteins; some RNAs can also catalyze rxns
3. Example of extreme catalytic efficiency: “catalase”
Reaction:
2 H2O2  2 H2O + O2
Catalyst
Relative rate
None
1
Fe3+
1,000
Catalase enzyme (heme)
109
(40,000,000/sec)
3D structure of catalase
Reaction:
2 H2O2  2 H2O + O2
Compound I
Reaction scheme of catalase
Enzymes
4. Another example of extreme catalytic efficiency:
“triosephosphate isomerase”
DHAP
Reaction
Free
energy
profile
DAP
3D structure of triosephosphate isomerase (TIM barrel)
The enzyme is so efficient that it is said to be catalytically perfect:
It is limited only by the rate the substrate can diffuse into and out
of the enzyme’s active site!
3D structure of triosephosphate isomerase (TIM barrel)
Uncatalyzed reaction:
G (free energy)
S
P
(transition state)
S‡
G‡
S
P
G
transition state
free energy
(activation energy)
overall reaction
free energy change
Reaction coordinate
1. G determines where equilibrium lies.
2. G‡ determines the rate at which equilibrium is achieved.
Enzyme-catalyzed reaction:
G (free energy)
S
E
P
S‡
ES‡
G‡
E+S
E+P
G
Reaction coordinate
1. Enzymes do not alter the equilibrium or G.
2. They accelerate reactions by decreasing G‡.
3. They accomplish this by stabilizing the transition state(s).
Models of Enzyme-Substrate Interaction
Emil Fischer, 19th century
Daniel Koshland, 20th century (sequential model for Hb coop.!)
The “Stickase” Enzyme
Factors Contributing to Rate Enhancement by Enzymes
1. Concentration - effective molarity in the active site.
k2 (second order rate constant)
k1 (first order rate constant)
Effective molarity = k1[s-1] / k2 [M-1s-1]
= k1 / k2 [M]
2. Orientation - increases the probability of correct bond or orbital alignment.
A
A
B
B
enzyme
3. Strain
- weakening of bonds by distortion
- exemplified by “stickase” model
4. Chemical catalysis (a catch-all term)
• major factor for most enzymes
• major types: acid-base, covalent, metal ion
• a given enzyme may use several types of
chemical catalysis in its mechanism
Combines with the final slide of the lecture
Chymotrypsin is a serine protease that
cleaves a peptide at Phe/Tyr/Trp (C) leaving a COO- on Phe/Tyr/Trp
R2
R22
R2
R2
To aid in the understanding of slide 15:
Acid-base forms of amino acid side chain