Download 13 respiration overview 9 30 05

Lecture 13
9/30/05
Cellular Respiration:
Harvesting Chemical Energy
Chapter 9
I.
General
Principles
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Figure 9.1
Lecture Outline
1. Regulation of Enzymes: competitive, allosteric, phosphorylation
2. Equilibrium
3. Digestion vs Metabolism: catabolism and anabolism
4. What is a metabolic pathway?
5. Feedback regulation of pathways
6. Catabolic pathways - stepping down the oxidation series of carbon
7. Harvesting energy from redox reactions
- substrate level phosphorylation ATP
– reducing equivalent carriers NADH + H+, FADH2
8. Example of a catabolic pathway: Fatty Acid Oxidation
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Reactions that proceed in a closed system
– Eventually reach equilibrium
Can do
Useful
work
∆G < 0
Cannot
Do
work
∆G = 0
(a) A closed hydroelectric system. Water flowing downhill turns a turbine
that drives a generator providing electricity to a light bulb, but only until
the system reaches equilibrium.
Figure 8.7 A
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Living systems = Open System
– Must have constant flow of materials in
– Constant Energy Input
Equilibrium to a living
system is called….
∆G < 0
(b) An open hydroelectric
system. Flowing water
keeps driving the generator
because intake and outflow
of water keep the system
from reaching equlibrium.
Figure 8.7
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Metabolism – totality of all chemical
reactions of an organism
digestion
Hydrolysis of polymers to monomers
No energy Harvested !
occurs “outside” the cell
catabolism – energy capture reactions
oxidize substrates, produce energy carriers
anabolism – energy utilizing reactions
use energy carriers, build things
Note: DG<0
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Metabolism: a series of favorable reactions
Inputs
∆G < 0
∆G < 0
∆G < 0
Figure 8.7
Metabolic Pathway:
Waste
Products
The product of each reaction becomes the reactant for a next, so6
no reaction reaches equilibrium
Metabolic Pathway
Enzymes work in series
Each enzyme carries out one reaction
Reactions in series constitute a Pathway
Enzyme 1
promotes reaction
A
B
Enzyme 2
promotes reaction
B
C
Enzyme 3
Enzyme 4
Enzyme 5
promotes reaction
promotes reaction
promotes reaction
C
D
E
D
E
F
Enzyme 6
promotes reaction
F
G
So as long as have A, G will be produced
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Each reaction is facilitated by a different enzyme
Chemistry of Life is organized
into Metabolic Pathways
Enzyme 1
Enzyme 2
A
D
C
B
Reaction 1
Enzyme 3
Reaction 2
Reaction 3
Product
Starting
molecule
A
A
AA
F F
B
E
C
F F
D
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Feedback Regulation
F
A
A
AA
F F
B
E
C
D
Enzymes can be regulated
Allosteric modulator ?
F F
“Plenty of
F
over Here,
Shut it OFF!”
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Initial substrate
(threonine)
Active site
available
thr
Threonine
in active site
Product
Of
Pathway
Is
Allosteric
Regulator
Of
First Enzyme
In Pathway
Enzyme 1
(threonine
deaminase)
Isoleucine
used up by
cell
Intermediate A
Feedback
inhibition
Active site of
enzyme 1 no
longer binds
threonine;
pathway is
switched off
Enzyme 2
Intermediate B
Enzyme 3
Intermediate C
Isoleucine
binds to
allosteric
site
Enzyme 4
Intermediate D
Enzyme 5
Figure 8.21
End product
(isoleucine)
ile
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Why so many steps in a pathway?
For example, oxidation of glucose:
C6H12O6 (glucose) + 6O2
DG= -686 kcal/mol
6CO2 + 6H2O
DH = -673 kcal/mol
TDS= -13 kcal/mol
in the cell, this is done in >21 steps!
Capture the energy in small packets
ie, 36 ATP units of 7.3 kcal
11
15 gallons
Of gasoline
Many
Small
Controlled
reactions
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catabolic pathway
Oxidize in discrete steps
Step down the oxidation series of carbon
some activation step
oxidation step, with energy harvest
reorganization step
oxidation step, another harvest
etc
yield product of pathway
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What is an OXIDATION?
For ionic species:
Reduced means
“rich” in electrons
Oxidized means
“fewer”
electrons
Fe++reduced
Oxidation: loss of eReduction : gain of e-
Fe+++oxidized
Organic Reductions
X + 2e- + 2H+
XH2
Organic Oxidation
YH2
Y + 2e- +2H+ 14
Reduced = High enthalpy
“few” bonds to oxygen
“many” bonds to hydrogen
Ease of
Removing
electrons
Oxidized
“few” bonds to oxygen
“many” bonds to hydrogen
electronegativity
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Highly
reduced
OXIDATION
series of carbon
Hydrocarbon chain
R-CH=CH2
Unsaturated hydrocarbon
Alcohol
Carbonyl
Carboxylic Acid
Carbon Dioxide
Highly oxidized
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In Metabolism:
Highly reduced
fully oxidized
CH3-CH2-CH2-(CH2)x-CH2-C-O + O2
Fatty acid
O
Partially reduced
carbohydrate
H2O + CO2 + energy
(captured)
fully oxidized
+ O2
H2O + CO2+ energy
(captured)
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R-CH2 -CH 3
R-CH=CH2
Catabolic Pathways
Progress down the
Oxidation Series
Of Carbon
R-CH2-CH2 -OH
R-CH2-C=O
H
R-CH2-C=O
OH
O=C=O
“adding O”
“H-H” removed
“H- + H+” removed
“2e- + H+ + H+” removed”
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REDOX Reactions
Oxidations always paired with reductions
If one thing gets oxidized,
another becomes reduced
Products
Reactants
Change the degree
of electron sharing
in covalent bonds
becomes oxidized
+
CH4
2O2
+
Energy
2 H2O
becomes reduced
O
O
C
O
H
O
O
H
H
H
C
+
CO2
H
Methane
(reducing
agent)
Oxygen
(oxidizing
agent)
Carbon dioxide
Water
Figure 9.3
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H
Carriers of Reducing Equivalents
CoEnzymes (CoFactors)
NAD+ nicotinamide adenine dinucleotide
NAD+ + H+ + 2e- -> NADH
NADP+ nicotinamide adenine dinucleotide phosphate
NADP+ + H+ + 2e- -> NADPH
FAD
flavin adenine dinucleotide
FAD + 2H+ + 2e- -> FADH2
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Electrons from organic compounds
Are usually first transferred to NAD+,
a coenzyme
2 e– + 2 H+
NAD+
NADH
O
H
NH2
H
C
N+
CH2
O
O P
O
O
+ 2[H]
(from food)
Nicotinamide
(oxidized form)
H
Reduction of NAD+
Oxidation of NADH
O
C
N
NH2
+
Nicotinamide
(reduced form)
O–
H
H
O P O– HO
O
2 e– + H+
CH2
OH
HO
NH2
N
N
H
N
O
H
HO
H
OH
N
H
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Figure 9.4
H+
2 e2 H+
e-
1 e1 H+
NAD+ to NADH
Carries 2e- and 1 H+
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NADP+ looks like this:
NADP+
NADPH
H+
H+
2e-
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FAD looks like this:
1 e1 H+
FAD to FADH2
Carries 2e- and 2 H+
1 e1 H+
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How harvest energy packets upon oxidation?
- high energy phosphate bonds
ATP, GTP production
substrate level phosphorylation
less usual form of energy harvest
-Carriers of reducing equivalents
Oxidized form – reduced form
NAD+ NADH + H+
FAD
FADH2
-Can cash in reduced carriers for ATP
oxidative phosphorylation
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Carriers of Energy potential
ATP – common energy
currency
“$$$”
High energy phosphate bonds
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Substrate Level Phosphorylation
Example:
“A”
Enzyme 1
NADH + H+
“B”
O
R- C-Pi
=
O
C
=
=
=
O O
R- C -C-OH
NAD+
Pi
=
High Energy
Compound
O
Oxidized to
Carbon Dioxide
=
“B”
O
R- C-Pi + ADP-OH
(ATP)
Enzyme 2
“C”
ADP -Pi
=
O
R- C27-OH
Energy of Oxidations “Captured”
in the FORMATION of ATP
Oxidized to ACID
How harvest energy packets upon oxidation?
$$$
- high energy phosphate bonds
ATP, GTP production
substrate level phosphorylation
less usual form of energy harvest
-Carriers of reducing equivalents
Oxidized form – reduced form
NAD+ NADH + H+
FAD
FADH2
Poker chips
-Can cash in reduced carriers for ATP
oxidative phosphorylation
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The Regeneration Energy Carriers
Energy carriers (ATP, NAD+, FAD) present
in only minute amounts
2e2H+
Cashed in
2e2H+
Captured in catabolism
NADH + H+
Energy from catabolism
(exergonic, energy yielding
processes)
Energy for cellular work
(endergonic, energyconsuming processes)
NAD+
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Let’s put it together
Step down oxidation series
Harvest energy in discrete packets
Fatty Acid Oxidation Pathway
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Start of Pathway
Priming Step (energy input)
CH3-CH2-R-CH2-CH2-C=O
Fatty acid
O-
CH3-CH2-R-CH2-CH2-C=O
Fatty acyl CoA
S-CoA
ATP + CoA-SH
ADP + Pi
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Fatty Acid Oxidation (b-oxidation)
Priming
Step
-steps down
oxidation
states of carbon
-captures
Reducing potential
NADH + H+
FADH2
Saturated
hydrocarbon
Ester
(acid)
Ketone
2e2 H+
removed
2e2 H+
removed
unsaturated
hydrocarbon
alcohol
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Net Result of Fatty Acid Oxidation Pathway
Fatty acid shortened by 2 carbon unit
2 carbon acid attached to CoA (acetyl CoA)
Oxidation of Carbon -CH2- to –C=O
to acid
S CoA
Capture reducing equivalents
2 NADH + H+
2 FADH2
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Summary
• Digestion, Metabolism, Catabolism, Anabolism
• Biochemical Pathway; feedback regulation
• Catabolic Pathways
- Step down oxidation series of carbon
- Harvest energy in discrete packets
•
ATP, NADH + H+, FADH2
• Fatty Acid Oxidation Pathway
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