Transcript Lecture 16

Review
1. Reaction mechanisms
2. Reducing sugars
3. Amino acid mutations and their effects
4. Lipids
Review
1. Reaction mechanisms
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Draw the catalytic amino acid side
chains with an eye for geometry
Remember the substrate and products
Use arrows to move to another panel
when you need to
For this class, focus on Attack!
Let’s go through the serine protease
mechanism again.
Review
2. Carbohydrates and Reducing sugars
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What does a reducing sugar have?
What makes non-reducing sugar?
When dealing with disaccharides or
oligosaccharides, draw the monomers
first and then connect them
appropriately
Review
3. Amino acid mutations
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What are the effect(s) of the mutation?
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Which kinetic parameters change?
What does that tell you?
Can you relate it to what we already know about
kinetics and inhibition?
You must think about the relationship
between the actual mutation, the physical
difference between the wild type and the
mutant as well as the effect of this
difference
Review
4. Lipids
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As usual, FIND THE FUNCTIONAL
GROUPS
Think about the role unsaturation plays in
the behaviour of the molecule
Where/when would you want to change the
saturation of the acyl chain?
What other types of linkage could you have
in acylglycerides? What effect(s) would the
different linkage have?
Electron Transfer
Types of biological redox reactions
1. Direct electron transfer:
2. H atom transfer
3. H:- (hydride) ion transfer
4. Direct reaction with O2 in some form
Electron Transfer
1. Direct electron transfer:
Fe+2 + Cu+3 --> Fe+3 + Cu+2
Oxidation Half Reaction: Fe+2 --> Fe+3 + 1eReduction Half Reaction: Cu+3 + 1e- --> Cu2+
The 2 half reactions make a RedOx couple
We can combine 2 half reactions from the
previous table and a reaction will occur as
long as the E°’ is POSITIVE
Electron Transfer
2. Hydrogen atom transfer
A Hydrogen atom has a single electron:
AH2  A + 2e- + 2H+
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AH2 is the hydrogen/electron donor
This is not an acid/base reaction, the H+ comes
from the removal of a hydrogen atom with its
electron, not just the proton
AH2 and A together constitute a conjugate redox
pair that can reduce another compound, B, or
redox pair (B/BH2) by transfer of hydrogen atoms:
AH2 + B  A + BH2
Electron Transfer
3. H:- (hydride) ion transfer
A hydride ion is a hydrogen atom with 2
electrons
Hydrides are transferred to NAD+ and
FADH2
We’ll look at these in just a bit…
Electron Transfer
4. Direct combination with oxygen
Oxygen combines with an organic reductant
and is covalently incorporated into the
product
Example: Oxidation of a hydrocarbon to an
alcohol
R-CH3 + 1/2 O2 --> R-CH2OH
The hydrocarbon is the electron donor and the
oxygen atom is the electron acceptor
Electron Carriers in Biological
Systems
In Many biological reactions, electrons are transferred
as hydrides to a Carrier Molecule
Nicotinamide adenine dinucleotide (NAD+) and Flavin
Adenine Dinucleotide (FAD2+) are the 2 primary
electron carrier molecules in cells
Nicotinamide adenine dinucleotide
NAD+, Nicotinamide
Adenine Dinucleotide,
is an electron acceptor
in catabolic pathways.
Nicotinamide
Adenine
Dinucleotide
-
O
is similar
except for Pi. NADPH
is e- donor in
synthetic pathways.
P
O
NH 2
+
N
CH 2
O
H
H
OH
OH
NH 2
O
N
N
O
P
nicotinamide
H
H
-
O
C
O
The nicotinamide ring,
derived from the
vitamin niacin,
accepts 2 e- & 1 H+ (a
hydride) in going to
the reduced state,
NADH.
NADP+/NADPH
H
O
CH 2
O
H
N
O
adenine
H
esterified to
Pi in NADP+
H
H
OH
N
OH
NAD+/NADH
H
O
H
H
C
C
NH2
+
N
O
 2 e- + H+
NH2
N
R
R
NAD+
NADH
The electron transfer reaction may be
summarized as :
NAD+ + 2e- + H+  NADH
It may also be written as:
NAD+ + 2e- + 2H+  NADH + H+
FAD (Flavin Adenine Dinucleotide), derived from the
vitamin riboflavin, functions as an e- acceptor.
The dimethylisoalloxazine ring undergoes
reduction/oxidation.
FAD accepts 2 e- + 2 H+ in going to its reduced state:
FAD + 2 e- + 2 H+  FADH2
Enzymes involved in RedOx Reactions
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Enzymes that catalyze RedOx reactions are generally
called Oxidoreductases
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This includes : Oxidases, Dehydrogenases,
Hydroperoxidases and Oxygenases.
Oxidases use oxygen as an electron acceptor
Dehydrogenases can’t use as an electron acceptor
Hydroperoxidases use H2O2 as a substrate
Oxygenases catalyse the direct transfer of O2 into the
substrate
Oxidases & dehydrogenases are involved in respiration;
hydroperoxidases neutralize free radicals & oxygenases
are involved in biotransformation
Oxidases
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Catalyze the removal of hydrogen from a
substrate with the involvement of oxygen as
a Hydrogen acceptor
Exist in two different forms :
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some of them are copper containing as,
Cytochrome oxidase - the terminal component
of ETC which transfer the e - to O2.
Other are flavoproteins such L – aminoacid
oxidase, xanthine oxidase
Dehydrogenases
Perform 2 main functions:
1. Transfer hydrogen from one substrate to
another in a coupled RedOx reaction
2. As components of Electron transport chain
Dehydrogenases use coenzymes –
nicotinamides & riboflavin to carry hydrogens
Haloperoxidases
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Includes 2 sets of enzymes : Catalase and
Peroxidases
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Peroxidases reduce H2O2 at the expense of several
other substances
H2O2 + AH2  2H2O + A
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Catalase uses H2O2 as electron acceptor &
electron donor
2H2O2  2H2O
Peroxisomes are rich in oxidases and catalases
Oxygenases
Catalyse the incorporation of O2 into subtrates in 2
steps
1. Oxygen is bound to the active site of the
enzyme
2. The O2 is then reduced or transferred to the
substrate
Consists of two sets of enzymes
• Dioxygenases : incorporate both atoms of
oxygen into the substrate
A + O2  AO2
• Monooxygenases : incorporates one atom of
oxygen into the substrate & the other is
reduced to water
AH + O2 + ZH2  AOH + H2O + Z