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) In the
cytosol?
glucose → → → → → pyruvate Why does
that make
6C 2x 3C 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 That’s not enough
AP Biology ATP for me!
4. Evolutionary perspective
Enzymes
Prokaryotes of glycolysis are
first cells had no organelles “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
ALL cells still utilize glycolysis
You mean
we’re related?
Do I have to invite
them over for
AP Biology the holidays?
5. glucose
Overview C-C-C-C-C-C
enzyme 2 ATP
10 reactions
enzyme 2 ADP
convert fructose-1,6bP
glucose (6C) to P-C-C-C-C-C-C-P
2 pyruvate (3C) enzyme enzyme
enzyme
produces: DHAP G3P
4 ATP & 2 NADH P-C-C-C C-C-C-P 2 NAD+
2H
consumes: 2Pi enzyme
2
2 ATP enzyme
net yield: 2Pi 4 ADP
enzyme
2 ATP & 2 NADH
pyruvate 4 ATP
DHAP = dihydroxyacetone phosphate
G3P Biology
AP
= glyceraldehyde-3-phosphate C-C-C
6. Glycolysis summary
ENERGY INVESTMENT endergonic
invest some ATP
-2 ATP
G3P
ENERGY PAYOFF C-C-C-P exergonic
harvest a little
4 ATP
ATP & a little NADH
like $$
in the
bank
NET YIELD net yield
2 ATP
AP Biology 2 NADH
7. 1st half of glycolysis (5 reactions)
CH2OH
Glucose “priming” Glucose
1
O
ATP
hexokinase
get glucose ready ADP CH2 O P
O
to split Glucose 6-phosphate
2
phosphorylate phosphoglucose
CH2 O P
glucose isomerase
O CH2OH
Fructose 6-phosphate
molecular 3
ATP
rearrangement phosphofructokinase
P O CH2 CH2 O P
ADP O
split destabilized Fructose 1,6-bisphosphate
glucose 4,5 aldolase
H
P O CH2 isomerase
C O Dihydroxyacetone C O
Glyceraldehyde 3
CHOH
CH2OH phosphate -phosphate (G3P)
CH2 O P
NAD+ Pi 6 Pi NAD+
NADH glyceraldehyde NADH
3-phosphate P O O
dehydrogenase
1,3-Bisphosphoglycerate 1,3-Bisphosphoglycerate CHOH
AP Biology
(BPG) (BPG) CH2 O P
8. 2nd half of glycolysis (5 reactions)
DHAP G3P
Energy Harvest P-C-C-C C-C-C-P
NAD+ Pi Pi NAD+
6
NADH production NADH NADH
G3P donates H ADP 7 ADP
phosphoglycerate O-
oxidizes the sugar ATP
kinase ATP C
reduces NAD+ 3-Phosphoglycerate 3-Phosphoglycerate CHOH
(3PG) (3PG)
NAD+ → NADH 8
CH2 O P
O-
ATP production phosphoglycero-
mutase C O
G3P → → → pyruvate 2-Phosphoglycerate 2-Phosphoglycerate H C O P
(2PG) (2PG) CH2OH
PEP sugar donates P
9 O-
“substrate level H2O enolase H2O
C O
phosphorylation” O
C P
ADP → ATP Phosphoenolpyruvate Phosphoenolpyruvate
CH2
(PEP) (PEP)
10 O-
ADP ADP
pyruvate kinase
Payola! ATP
C O
ATP
Finally some C O
AP Biology ATP! Pyruvate Pyruvate CH3
9. Substrate-level Phosphorylation
In the last steps of glycolysis, where did
the P come from to make ATP?
the sugar substrate O
H
(PEP) enolase
2
9
H2O
O-
C O
O
P is transferred Phosphoenolpyruvate
(PEP)
Phosphoenolpyruvate
(PEP)
C
CH2
P
from PEP to ADP ADP 10 ADP
O-
kinase enzyme ATP
pyruvate kinase
ATP
C O
C O
ADP → ATP Pyruvate Pyruvate CH3
ATP
I get it!
The Pi came
directly from
the substrate!
AP Biology
10. Energy accounting of glycolysis
2 ATP 2 ADP
glucose → → → → →
pyruvate
6C 2x 3C
4 ADP 4 ATP All that work!
And that’s all
I get?
2 NAD+ 2 But
glucose has
so much more
Net gain = 2 ATP + 2 NADH to give!
some energy investment (-2 ATP)
small energy return (4 ATP + 2 NADH)
1 6C sugar → 2 3C sugars
AP Biology
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 glucose → → → → pyruvate
6C 2x 3C
O2
Hard way
O2 to make
a living!
AP Biology
O2
12. But can’t stop there! DHAP G3P
NAD+ Pi Pi NAD+
raw materials → products NADH
NAD+ Pi 6 Pi NADH
NAD+
NADH 1,3-BPG 1,3-BPG NADH
ADP 7 ADP
Glycolysis ATP ATP
3-Phosphoglycerate 3-Phosphoglycerate
(3PG) (3PG)
glucose + 2ADP + 2Pi + 2 NAD+ → 2 pyruvate + 2ATP + 2NADH
8
2-Phosphoglycerate 2-Phosphoglycerate
Going to run out of NAD+ (2PG)
9
(2PG)
H2O H2O
without regenerating NAD+,
energy production would stop! Phosphoenolpyruvate Phosphoenolpyruvate
(PEP) (PEP)
another molecule must accept HADP 10 ADP
from NADH ATP ATP
so Pyruvate Pyruvate
AP Biology NAD+ is freed up for another round
13. How is NADH recycled to NAD+?
with oxygen without oxygen
Another molecule aerobic respiration anaerobic respiration
must accept H pyruvate
“fermentation”
from NADH
H2O NAD+
CO2
O2 NADH NADH acetaldehyde
recycle acetyl-CoA NADH
NAD+
NADH
lactate NAD+
lactic acid
fermentation
which path you Krebs
ethanol
use depends on cycle
alcohol
who you are…
AP Biology fermentation
14. Fermentation (anaerobic)
Bacteria, yeast
pyruvate → ethanol + CO2
3C 2C 1C
NADH NAD+
back to glycolysis→→
beer, wine, bread
Animals, some fungi
pyruvate → lactic acid
3C 3C
NADH NADback to glycolysis→→
+
AP Biology cheese, anaerobic exercise (no O2)
15. bacteria
Alcohol Fermentation yeast
recycle
pyruvate → ethanol + CO2 NADH
3C 2C 1C
NADH NAD+ back to glycolysis→→
Dead end process
at ~12% ethanol,
kills yeast
can’t reverse the
reaction
Count the
carbons!
AP Biology
16. animals
some fungi
Lactic Acid Fermentation recycle
O2
pyruvate → lactic acid
→
NADH
3C 3C
NADH NAD+ back to glycolysis→→
Reversible process
once O2 is available,
lactate is converted
back to pyruvate by
the liver
Count the
carbons!
AP Biology
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+
H+ H+ H+
And how do we do that? 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+
But… Have we done that yet?
AP Biology
20. NO!
There’s still more
to my story!
Any Questions?
AP Biology 2007-2008
Editor's Notes
Why does it make sense that this happens in the cytosol? Who evolved first?
The enzymes of glycolysis are very similar among all organisms. The genes that code for them are highly conserved. They are a good measure for evolutionary studies. Compare eukaryotes, bacteria & archaea using glycolysis enzymes. Bacteria = 3.5 billion years ago glycolysis in cytosol = doesn’t require a membrane-bound organelle O 2 = 2.7 billion years ago photosynthetic bacteria / proto-blue-green algae Eukaryotes = 1.5 billion years ago membrane-bound organelles! Processes that all life/organisms share: Protein synthesis Glycolysis DNA replication
1st ATP used is like a match to light a fire… initiation energy / activation energy. Destabilizes glucose enough to split it in two
Glucose is a stable molecule it needs an activation energy to break it apart. phosphorylate it = Pi comes from ATP. make NADH & put it in the bank for later.
And that’s how life subsisted for a billion years. Until a certain bacteria ”learned” how to metabolize O 2 ; which was previously a poison. But now pyruvate is not the end of the process Pyruvate still has a lot of energy in it that has not been captured. It still has 3 carbons bonded together! There is still energy stored in those bonds. It can still be oxidized further.
So why does glycolysis still take place?
Count the carbons!! Lactic acid is not a dead end like ethanol. Once you have O 2 again, lactate is converted back to pyruvate by the liver and fed to the Kreb’s cycle.