1. Cellular Respiration
Stage 1:
Glycolysis
AP Biology
2007-2008

2. What’s the
point?
The point
is to make
ATP!
ATP
AP Biology
2007-2008

3. Glycolysis
 Breaking down glucose

“glyco – lysis” (splitting sugar)
glucose → → → → → pyruvate
2x 3C
6C
In the
cytosol?
Why does
that make
evolutionary
sense?

ancient pathway which harvests energy
 where energy transfer first evolved
 transfer energy from organic molecules to ATP
 still is starting point for ALL cellular respiration

but it’s inefficient
 generate only 2 ATP for every 1 glucose

occurs in cytosol
AP Biology
That’s not enough
ATP for me!

4. Evolutionary perspective
 Prokaryotes

first cells had no organelles
Enzymes
of glycolysis are
“well-conserved”
 Anaerobic atmosphere


life on Earth first evolved without free oxygen (O2)
in atmosphere
energy had to be captured from organic molecules
in absence of O2
 Prokaryotes that evolved glycolysis are ancestors
of all modern life

AP Biology
ALL cells still utilize glycolysis
You mean
we’re related?
Do I have to invite
them over for
the holidays?

5. Overview
glucose
C-C-C-C-C-C
10 reactions
enzyme
enzyme
2 ATP
2 ADP
convert
fructose-1,6bP
glucose (6C) to
P-C-C-C-C-C-C-P
enzyme
enzyme
2 pyruvate (3C)
enzyme
 produces:
DHAP
G3P
4 ATP & 2 NADH P-C-C-C C-C-C-P
2H
 consumes:
2Pi enzyme
2 ATP
enzyme
 net yield:
2Pi
enzyme
2 ATP & 2 NADH

DHAP = dihydroxyacetone phosphate
AP
G3P Biology
= glyceraldehyde-3-phosphate
pyruvate
C-C-C
2 NAD+
2
4 ADP
4 ATP

6. Glycolysis summary
endergonic
invest some ATP
ENERGY INVESTMENT
-2 ATP
ENERGY PAYOFF
G3P
C-C-C-P
4 ATP
exergonic
harvest a little
ATP & a little NADH
like $$
in the
bank
NET YIELD
AP Biology
net yield
2 ATP
2 NADH

7. 1st half of glycolysis (5 reactions)
Glucose “priming”

get glucose ready
to split
 phosphorylate
ADP
P
CH2 O
O
P O
P
CH2
CH2
O
CH2OH
Fructose 1,6-bisphosphate
O CH2
C
4,5 aldolase
isomerase
O Dihydroxyacetone
CH2OH phosphate
Glyceraldehyde 3
-phosphate (G3P)
Pi
NAD+
Pi
6
glyceraldehyde
NADH
NADH
3-phosphate
P
dehydrogenase
1,3-Bisphosphoglycerate 1,3-Bisphosphoglycerate
(BPG)
(BPG)
NAD+
AP Biology
O
CH2 O
O
Glucose 6-phosphate
2
Fructose 6-phosphate
3
ATP
phosphofructokinase
split destabilized
glucose
P
ADP
phosphoglucose
isomerase
glucose
 molecular
rearrangement

CH2OH
Glucose
1
ATP
hexokinase
H
C O
CHOH
CH2 O
O
P
O
CHOH
CH2 O
P
O
P

8. 2nd half of glycolysis (5 reactions)
DHAP
P-C-C-C
Energy Harvest

NADH production





G3P donates H
oxidizes the sugar
reduces NAD+
NAD+ → NADH
Pi
NAD+
phosphorylation”
 ADP → ATP
AP Biology
Payola!
Finally some
ATP!
Pi
6
NAD+
NADH
NADH
7
phosphoglycerate
kinase
ADP
ATP
3-Phosphoglycerate
(3PG)
ADP
ATP
3-Phosphoglycerate
(3PG)
8
phosphoglyceromutase
ATP production
 G3P → → → pyruvate
 PEP sugar donates P
 “substrate level
G3P
C-C-C-P
2-Phosphoglycerate
(2PG)
Phosphoenolpyruvate
(PEP)
ADP
H2O
Phosphoenolpyruvate
(PEP)
10
pyruvate kinase
ADP
O P
ATP
Pyruvate
C O
H C O
CH2OH
P
OC
C
CH2
O
O
OC
ATP
Pyruvate
CHOH
CH2
O-
2-Phosphoglycerate
(2PG)
9
enolase
H2O
OC
O
C O
CH3
P

9. Substrate-level Phosphorylation
 In the last steps of glycolysis, where did
the P come from to make ATP?

9
the sugar substrate O
(PEP) enolase
H
H2O
2
P is transferred
from PEP to ADP
kinase enzyme
ADP → ATP
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Phosphoenolpyruvate
(PEP)
ADP
Phosphoenolpyruvate
(PEP)
10
pyruvate kinase
Pyruvate
I get it!
The Pi came
directly from
the substrate!
Pyruvate
C
C
CH2
O
O
OC
ATP
ATP
ATP
ADP
O-
O
C O
CH3
P

10. Energy accounting of glycolysis
2 ATP
2 ADP
glucose → → → → →
pyruvate
2x 3C
6C
4 ADP
4 ATP
2 NAD+
2
 Net gain = 2 ATP + 2 NADH


All that work!
And that’s all
I get?
But
glucose has
so much more
to give!
some energy investment (-2 ATP)
small energy return (4 ATP + 2 NADH)
AP Biology
 1 6C sugar → 2 3C sugars

11. Is that all there is?
 Not a lot of energy…

for 1 billon years+ this is how life on Earth
survived
 no O2 = slow growth, slow reproduction
 only harvest 3.5% of energy stored in glucose
 more carbons to strip off = more energy to harvest
O2
O2
O2
O2
AP Biology
O2
glucose → → → → pyruvate
2x 3C
6C
Hard way
to make
a living!

12. But can’t stop there!
G3P
DHAP
NAD+
raw materials → products
NADH
NAD+
NADH
Pi
6
1,3-BPG
NAD+
Pi
NADH
NAD+
1,3-BPG
NADH
7
ADP
Glycolysis
Pi
Pi
ADP
ATP
ATP
3-Phosphoglycerate
(3PG)
3-Phosphoglycerate
(3PG)
2-Phosphoglycerate
(2PG)
2-Phosphoglycerate
(2PG)
glucose + 2ADP + 2Pi + 2 NAD+ → 2 pyruvate + 2ATP + 2NADH
8
 Going to run out of NAD+


H2O
9
without regenerating NAD+,
energy production would stop! Phosphoenolpyruvate
(PEP)
another molecule must accept HADP
10
from NADH
ATP
 so
AP Biology
NAD+ is freed up for another round
Pyruvate
H2O
Phosphoenolpyruvate
(PEP)
ADP
ATP
Pyruvate

13. How is NADH recycled to NAD+?
Another molecule
must accept H
from NADH
H2O
O2
recycle
NADH
with oxygen
without oxygen
aerobic respiration
anaerobic respiration
“fermentation”
pyruvate
NAD+
NADH
acetyl-CoA
CO2
NADH
NAD+
lactate
acetaldehyde
NADH
NAD+
lactic acid
fermentation
which path you
use depends on
AP Biology
who you are…
Krebs
cycle
ethanol
alcohol
fermentation

14. Fermentation (anaerobic)
 Bacteria, yeast
pyruvate → ethanol + CO2
3C
NADH
2C
NAD+
 beer, wine, bread
1C
back to glycolysis→→
 Animals, some fungi
pyruvate → lactic acid
3C
NADH
AP Biology

3C
+
NADback to glycolysis→→
cheese, anaerobic exercise (no O2)

15. Alcohol Fermentation
pyruvate → ethanol + CO2
3C
NADH
2C
NAD+ back to glycolysis→→
 Dead end process
 at ~12% ethanol,
kills yeast
 can’t reverse the
reaction
Count the
carbons!
AP Biology
1C
bacteria
yeast
recycle
NADH

16. Lactic Acid Fermentation
pyruvate → lactic acid
→
3C
NADH
3C
NAD+ back to glycolysis→→
 Reversible process
 once O2 is available,
lactate is converted
back to pyruvate by
the liver
Count the
carbons!
AP Biology
O2
animals
some fungi
recycle
NADH

17. Pyruvate is a branching point
Pyruvate
O2
O2
fermentation
anaerobic
respiration
mitochondria
Krebs cycle
aerobic respiration
AP Biology

18. What’s the
point?
The point
is to make
ATP!
ATP
AP Biology
2007-2008

19. H+
And how do we do that? H
+
H+
H+
H+
H
+
H+
H+
 ATP synthase
set up a H+ gradient
 allow H+ to flow
through ATP synthase
 powers bonding
of Pi to ADP

ADP + P
ADP + Pi → ATP
ATP
H+
AP Biology
But… Have we done that yet?

20. NO!
There’s still more
to my story!
Any Questions?
AP Biology
2007-2008