Chapter 6.1 and 6.2: Introduction to Enzymes
-
Upload
chanda-norris -
Category
Documents
-
view
103 -
download
3
description
Transcript of Chapter 6.1 and 6.2: Introduction to Enzymes
Chapter 6.1 and 6.2: Introduction to Enzymes
CHEM 7784
Biochemistry
Professor Bensley
CHAPTER 6.1 and 6.2 Introduction to Enzymes and How
Enzymes Work
– Physiological significance of enzymes– Origin of catalytic power of enzymes– Chemical mechanisms of catalysis
Today’s Objectives: (To learn and understand the)
What are Enzymes?
• Enzymes are catalytically active biological macromolecules
• Most enzymes are globular proteins, however some RNA (ribozymes, and ribosomal
RNA) also catalyze reactions
• Study of enzymatic processes is the oldest field of biochemistry, dating back to late 1700s
Why Biocatalysis?• Higher reaction rates• Greater reaction specificity• Milder reaction conditions• Capacity for regulation
COO
OH
O COO
COO
O COO
NH2
OOCCOO
O
OH
OH
COO
NH2
COO
-
-
-
-
-
-
--
Chorismate mutase
• Metabolites have many potential pathways of decomposition
• Enzymes make the desired one most favorable
Quiz Question 29
In order to function properly, some enzymes require the presence of an additional chemical component such
as inorganic ions (Zn2+ or Fe2+). These inorganic ions are known as
for enzymes.
Quiz Question 30
Chymotrypsin is an enzyme that cleaves peptide bonds. It most likely, therefore, belongs to which class of enzymes?
a)Transferases b) Ligases
c) Isomerases d) Hydrolases
Classes of enzymes
1. Oxidoreductases = catalyze oxidation-reduction reactions (Transfer of electrons) (NADH)
2. Transferases = catalyze transfer of functional groups from one molecule to another.
3. Hydrolases = catalyze hydrolytic cleavage (transfer of functional groups to water)
4. Lyases = catalyze removal of a group from or addition of a group to a double bond, or other cleavages involving electron rearrangement.
5. Isomerases = catalyze intermolecular rearrangement.
6. Ligases = catalyze reactions in which two molecules are joined.
Enzymes named for the substrates and type of reaction
E + S ES E + Pk1
k-1
k2
k-2
E S+ E S E + P
Rate Acceleration
• The enzyme lowers the activation barrier compared to the uncatalyzed aqueous reaction
• In theory, the enzyme may also facilitate the tunneling through the barrier. This may be important for electrons.
How to Lower G?
1. Enzymes organize reactive groups into proximity
2. Enzymes bind transition states best (LargelyaH‡ effect)
Support for the Proximity Model
• The rate of anhydride formation from esters and carboxylates shows a strong dependence on proximity of two reactive groups
Support for TS Stabilization
• Structure-activity correlations in chymotrypsin substrates
Illustration of TS Stabilization Idea:Imaginary Stickase
How is TS Stabilization Achieved?
acid-base catalysis: give and take protonscovalent catalysis: change reaction pathsmetal ion catalysis: use redox cofactors, pKa
shifterselectrostatic catalysis: preferential
interactions with TS
Acid-base Catalysis: Chemical Example
Consider ester hydrolysis:
R
O
C
H
3
O
R
O
C
H
3
O
O
H
H
+
R
O
O
H
+ H-OH + + CH3OH
Water is a poor nucleophile, and methanol is a poor leaving group
Aqueous hydrolysis can be catalyzed either by acids or by bases
Enzymes can do acid and base catalysis simultaneously
Amino Acids in General Acid-Base catalysis
•The anhydride hydrolysis reaction is catalyzed by pyridine, a better nucleophile than water (pKa=5.5).
•Hydrolysis is accelerated because of charge loss in the transition state makes pyridine a good leaving group.
Covalent Catalysis: Chemical Example
CH3O
O
CH3
O
CH3O
O
CH3O
O
H+- -+
H2O
slow + 2
CH3O
O
CH3
O
N
CH3O
O
N CH3
O
OH H
N CH3
O
OHN
CH3O
O
H+
..fast
-+ +
..
+
-
-+..
Covalent Catalysis: In Enzymes• Proteases and peptidases
– chymotrypsin, elastase, subtilisin– reactive serine nucleophile
• Some aldehyde dehydrogenase– glyceraldehyde-3-phosphate dehydrogenase– reactive thiolate nucleophile
• Aldolases and decarboxylases– amine nucleophile
• Dehalogenases– carboxylate nucleophile
N
OH
ON
S
ON O
NH2
N O
O
O-
-