Cellular Respiration
Stage 1:
Glycolysis

AP Biology

2007-2008
What’s the
point?

The point
is to make
ATP!

ATP
AP Biology

2007-2008
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!
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?
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
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
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
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
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

AP Biology

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
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
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!
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
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
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)
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
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
Pyruvate is a branching point
Pyruvate
O2

O2

fermentation
anaerobic
respiration

mitochondria
Krebs cycle
aerobic respiration

AP Biology
What’s the
point?

The point
is to make
ATP!

ATP
AP Biology

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

AP Biology

2007-2008

34 ch09respiration22008

  • 1.
  • 2.
    What’s the point? The point isto make ATP! ATP AP Biology 2007-2008
  • 3.
    Glycolysis  Breaking downglucose  “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  firstcells 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 2ADP 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 someATP 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 ofglycolysis (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 ofglycolysis (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  Inthe 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 AP Biology 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 ofglycolysis 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 allthere 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 stopthere! 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 NADHrecycled 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 abranching point Pyruvate O2 O2 fermentation anaerobic respiration mitochondria Krebs cycle aerobic respiration AP Biology
  • 18.
    What’s the point? The point isto make ATP! ATP AP Biology 2007-2008
  • 19.
    H+ And how dowe 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 tomy story! Any Questions? AP Biology 2007-2008

Editor's Notes

  • #4 Why does it make sense that this happens in the cytosol? Who evolved first?
  • #5 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 O2 = 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
  • #6 1st ATP used is like a match to light a fire… initiation energy / activation energy. Destabilizes glucose enough to split it in two
  • #7 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.
  • #11 And that’s how life subsisted for a billion years. Until a certain bacteria ”learned” how to metabolize O2; 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.
  • #12 So why does glycolysis still take place?
  • #15 Count the carbons!! Lactic acid is not a dead end like ethanol. Once you have O2 again, lactate is converted back to pyruvate by the liver and fed to the Kreb’s cycle.