Lecture 14 10/3/05
Cellular Respiration:
Harvesting Chemical Energy
Chapter 9
II.
Catabolic
Oxidative
Pathways
1
Lecture Outline
1. Review Fatty Acid Oxidation Pathway
2. Oxidation of Monosaccharides (Glycolysis Pathway)
3. Mitochondrial Spaces: Matrix, Intermembrane Space
4. Oxidation of Pyruvate
5. Complete oxidation of Carbon from FA ox & glycolysis
– TCA Cycle (Kreb’s Cycle)
6. Cashing in the “accumulated” Reducing Equivalents -
Oxidative Phosphorylation
2
Fatty Acid Oxidation (b-oxidation) in Mitochondria
Priming Saturated
Step hydrocarbon
2e-
2 H+
-steps down removed
Ester
oxidation (acid)
states of carbon unsaturated
hydrocarbon
-captures
Reducing potential
NADH + H+
FADH2 Ketone
2e-
alcohol
2 H+ 3
removed
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
4
Glycolysis Another catabolic pathway
Oxidation of monosaccharides
(polysaccharides digested to monosaccharides; no energy harvested)
Hexoses (like glucose)
6 carbon sugar
Aldehyde with 5 alcohols
(Two)
3 carbon acid
with a ketone
oxidized to pyruvic acid
5
Glycolysis consists of two major phases
Energy investment phase
Glucose
Energy investment phase
(Priming Steps) 2 ATP + 2 P 2 ATP used
Energy payoff phase
4 ADP + 4 P 4 ATP formed
Energy payoff phase
2 NAD+ + 4 e- + 4 H + 2 NADH + 2 H+
2 Pyruvate + 2 H2O
Net Harvest Glucose 2 Pyruvate + 2 H2O
Of Pathway 4 ATP formed – 2 ATP used 2 ATP + 2 H+
2 NADH
6
2 NAD+ + 4 e– + 4 H +
Figure 9.8
CH2OH
Glycolysis
H H
H
HO H
HO OH
H OH
Energy Priming Stage
Glucose
ATP 1
Hexokinase
ADP
Add Pi to #6 carbon CH2OH
H
H
P
O H
OH H
HO
H OH
Glucose-6-phosphate
Rearrange
2
Phosphoglucoisomerase
CH2O P
O CH2OH
H HO
H HO
HO H
Fructose-6-phosphate
Add Pi to #1 carbon
3
ATP
Phosphofructokinase
ADP
P O CH2 O CH2 O P
Split into two
HO
H OH
HO H
2 of
3 carbon units
Fructose-
1, 6-bisphosphate
4
these
Aldolase
5 H
P O CH2 Isomerase C O
rearrange
C O
CHOH
CH2OH
CH2 O P
Dihydroxyacetone 7
Glyceraldehyde-
phosphate 3-phosphate
Figure 9.9 A
Glycolysis Two
6
2 NAD+
Triose phosphate
dehydrogenase
Energy PAYOFF Stage Of
2 NADH 2 Pi
+ 2 H+
2
P O C O
these
CHOH
CH2 O P
Oxidize #1 aldehyde to Acid
1, 3-Bisphosphoglycerate
2 ADP
7
NADH + H+, high energy phosphate
Phosphoglycerokinase
2 ATP
2 O–
Harvest Phosphate C
CHOH
Substrate Level Phosphorylation CH2 O
3-Phosphoglycerate
P
ATP made
8
Phosphoglyceromutase
rearrange
2 O–
C O
H C O P
CH2OH
2-Phosphoglycerate
9
Oxidize #2 alcohol to Ketone 2 H2O Enolase
2 O–
High energy phosphate
C O
C O P
CH2
Phosphoenolpyruvate
2 ADP
10
Pyruvate kinase
Harvest Phosphate pyruvate
2 ATP
2 O–
Substrate Level Phosphorylation C
C
O
O
8
ATP made Figure 9.8 B
CH3
Pyruvate
Net Result of Glycolysis Pathway
6 Carbon Sugar oxidized to
TWO Pyruvate (acid with ketone)
Net yield of 2 ATP produced
by substrate level phosphorylation
Capture reducing equivalents
2 NADH + H+
9
Fate of the 2 Pyruvate molecules?
enter the mitochondrion for further oxidation
produce 6 CO2
Pathway called the TCA cycle
What does it mean to “get into” the
mitochondrion?
Glycolysis occurs in cytosol 10
Mitochondria
Functional Spaces
Matrix
Inner
Mito
Membrane
Outer
Mitochondrial
Folds of
Inner membrane Membrane
Called
Cristae Intermembrane
Space 11
Electrons Electrons carried
carried via NADH and
via NADH FADH2
Oxidative
Glycolsis Citric phosphorylation:
acid electron transport
Glucose Pyruvate cycle and
chemiosmosis
Cytosol
Mitochondrion
ATP ATP ATP
Substrate-level
Substrate-level Oxidative
phosphorylation
phosphorylation phosphorylation
Figure 9.6
12
Matrix
Contains DNA
Contains bacterial-like ribosomes
Site of three important oxidative reaction cycles
Fatty Acid Oxidation
Pyruvate oxidation
TCA Cycle
Intermembrane Space
Reservoir to hold H+ ions
Inner Mitochondrial Membrane
Densely packed with proteins
Site of “oxidative phosphorylation”
electron transport and ATP production13
Oxidation of Pyruvate to Acetyl CoA
Familiar?
CYTOSOL MITOCHONDRION
NAD+ NADH + H+
O–
S CoA
2
C O
C O
C O
CH3
1 3
Acetyl
CH3
Acetyl CoA
pyruvate
Pyruvate CO2 Coenzyme A
CoA
Transport protein
14
Figure 9.10
Digestion
Proteins Carbohydrates Fats
Amino Sugars Glycerol Fatty
acids acids
Glycolysis
Glucose
Catabolic
Glyceraldehyde-3- P
Pathways
NH3 Pyruvate
Acetyl CoA
Interconnected
Pathways
Citric
acid
cycle
Common
Figure 9.19
Oxidative
phosphorylation Intermediates
15
Pyruvate
Oxidation
Tri Carboxylic Acid
TCA Cycle
Kreb’s Cycle
16
TCA Cycle
Stepping down the Oxidation Series of Carbons
-Acid to CO2
-Ketone to acid (thioester)
- saturated to unsaturated
- unsaturated to alcohol
- alcohol to ketone or carboxylic acid
- decarboxylation
Capture reducing equivalents
NAD+ 2e- + 2H+ NADH + H+
FAD 2e- + 2H+ FADH2
17
TCA Cycle Pyruvate
(from glycolysis,
Glycolysis Citric
acid
cycle
Oxidative
phosphorylation
2 molecules per glucose)
•Oxidize the 2 carbon unit ATP ATP ATP
Acetyl CoA CO2
To 2 CO2
CoA
NADH
•Five key oxidation steps
+ 3 H+ Acetyle CoA
CoA
3 NADH + H+ CoA
1 FADH2
1 GTP Citric
Per 2 carbon unit acid
cycle
2 CO2
FADH2 3 NAD+
Regenerate the initial
FAD 3 NADH
+ 3 H+
4 carbon acid
ADP + P i
ATP
repeat
18
Figure 9.11
Reactions of the TCA cycle pathway
Note oxidation points
Capture of 3 NADH + H+
Capture of 1 FADH2
Capture of 1 high energy phosphate bond (GTP)
per 2 carbon unit
So some GTP harvested,
but a lot of reducing equivalents accumulated
these are worth a lot more ATP
How? 19
What good are “accumulated” reducing equivalents?
H2 + 1/2 O2
H2 = 2e- 2H+
Free energy, G
Explosive
release of
heat and light
energy
2H2 + O2 = H2O + BOOM!
Figure 9.5 A H2O
20
The Regeneration Energy Carriers
Energy carriers (ATP, NAD+, FAD) present
in only minute amounts
Only limited amounts of reducing equiv carriers
must “cash them in” - oxidize them
2e-
2e- 2H+
2H+ Cashed in
Captured in catabolism
Electron transport
– oxidizes NADH and FADH2 NADH + H+
back to NAD+ and FAD
Energy from catabolism Energy for cellular work
(exergonic, energy yielding (endergonic, energy-
processes) consuming processes)
NAD+ 21
Mitochondrial Functions
Oxidize compounds to CO2 + H2O
Fatty acid Oxidation
Produce
Oxidation of Pyruvate reduced carriers
TCA Kreb’s Cycle NADH & FADH2
Generate >90% of Typical Cell’s ATP
Oxidative Phosphorylation
“electron transport”
ATP synthesis Oxidize reduced carriers
to produce ATP or equiv
22
Next time
How cash in the NADH + H+ and FADH2
“poker chips” for ATP
Oxidative Phosphorylation
23
Summary
-FA oxidation in matrix of mitochondrion
-Glycolysis (ox of sugar) in cytosol
-Oxidation of pyruvate in matrix of mitochondrion
-TCA cycle (oxidation of acetyl CoA) in matrix
- “accumulate” reducing equivalent carriers
- must “cash in” for ATP – oxidative Phosphorylation
Electrons Electrons carried
carried via NADH and
via NADH FADH2
Citric
Glycolsis acid Oxidative
Glucose Pyruvate phosphorylation
cycle
Cytosol Mitochondrion
ATP ATP ATP
Substrate-level 24
Substrate-level Oxidative
phosphorylation phosphorylation phosphorylation
Figure 9.6