bio 98 - leture 8 enzymes i. enzymes 1. selective catalysis and regulation of metabolic...
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Bio 98 - Leture 8
Enzymes I
Enzymes1. 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 rxns3. Example of extreme catalytic efficiency: “catalase”
Reaction: 2 H2O2 2 H2O + O2
Catalyst Relative rateNone 1Fe3+ 1,000Catalase enzyme (heme) 109 (40,000,000/sec)
3D structure of catalase
Reaction scheme of catalase
Reaction: 2 H2O2 2 H2O + O2
Compound I
Enzymes
4. Another example of extreme catalytic efficiency: “triosephosphate isomerase”
Reaction
Freeenergyprofile
DHAP 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:
1. G determines where equilibrium lies. 2. G‡ determines the rate at which equilibrium is achieved.
transition statefree energy (activation energy)
overall reactionfree energy changeG
(fr
ee e
nerg
y)
Reaction coordinate
P
S‡
S
(transition state)
G‡
G
S P
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).
Enzyme-catalyzed reaction:
G (
free
ene
rgy)
Reaction coordinate
E+P
ES‡
E+S G‡
G
S‡
S PE
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 Enzymes1. Concentration - effective molarity in the active site.
2. Orientation - increases the probability of correct bond or orbital alignment.
enzymeA B
A B
k1 (first order rate constant)
Effective molarity = k1[s-1] / k2 [M-1s-1] = k1 / k2 [M]
k2 (second order rate constant)
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
R2
Chymotrypsin is a serine protease that cleaves a peptide at Phe/Tyr/Trp (C) -
leaving a COO- on Phe/Tyr/Trp
2R2
R2
R2
To aid in the understanding of slide 15:Acid-base forms of amino acid side chain