Cellular Respiration

Stage 1: Glycolysis
Cellular Respiration
Glycolysis
u Breaking down glucose
u “glyco – lysis” (splitting sugar)

glucose ® ® ® ® ® pyruvate
6C 2x 3C

u ancient pathway which harvests energy

u but it’s inefficient

v generate only 2 ATP for every 1 glucose
u occurs in cytosol
Evolutionary perspective
u Prokaryotes
u first cells had no organelles
u Anaerobic atmosphere
u life on Earth first evolved without free oxygen
(O2) in atmosphere
u energy had to be captured from organic molecules
in absence of O2
u Prokaryotes that evolved glycolysis are ancestors
of all modern life
u ALL cells still utilize glycolysis
 glucose
Overview C-C-C-C-C-C
enzyme 2 ATP
10 reactions enzyme 2 ADP
u convert fructose-1,6bP
glucose (6C) to P-C-C-C-C-C-C-P
2 pyruvate (3C) enzyme enzyme
enzyme
u produces: DHAP G3P
4 ATP & 2 NADH P-C-C-C C-C-C-P
2H 2 NAD+
u consumes: 2Pi enzyme
2 ATP 2 NADH
enzyme
u net yield:
2Pi 4 ADP
2 ATP & 2 NADH enzyme

pyruvate 4 ATP
DHAP = dihydroxyacetone phosphate
G3P = glyceraldehyde-3-phosphate C-C-C
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

NET YIELD net yield

ü2 ATP
ü2 NADH
 1st half of glycolysis (5 reactions)
CH2OH
Glucose O
1
ATP
hexokinase
ADP CH2 O P
O
Glucose 6-phosphate
2
phosphoglucose CH2 O P
isomerase O CH2OH
Fructose 6-phosphate
Glucose “priming” ATP
3
phosphofructokinase
P O CH2 CH2 O P
ADP O
Fructose 1,6-bisphosphate
4,5 aldolase
H
P O CH2 isomerase
C O
C O Dihydroxyacetone Glyceraldehyde 3
CHOH
CH2OH phosphate -phosphate (G3P)
CH2 O P
NAD+ Pi 6 Pi NAD+
NADH glyceraldehyde NADH
3-phosphate P O O
dehydrogenase
CHOH
1,3-Bisphosphoglycerate 1,3-Bisphosphoglycerate
(BPG) (BPG) CH2 O P
 2nd half of glycolysis (5 reactions)
DHAP G3P
Energy Harvest P-C-C-C C-C-C-P
NAD+ Pi Pi NAD+
6
u NADH production NADH NADH

ADP 7 ADP
phosphoglycerate O-
kinase ATP
ATP C
3-Phosphoglycerate 3-Phosphoglycerate CHOH
(3PG) (3PG)
u ATP production 8
CH2 O P

phosphoglycero- O-
mutase C O
2-Phosphoglycerate 2-Phosphoglycerate H C O P
(2PG) (2PG) CH2OH
9 O-
H2O enolase H2O
C O
C O P
u “substrate level Phosphoenolpyruvate Phosphoenolpyruvate
CH2
(PEP) (PEP)
phosphorylation”
10 O-
ADP ADP
pyruvate kinase C O
ATP ATP
C O
Pyruvate Pyruvate CH3
 Substrate-level Phosphorylation
u In the last steps of glycolysis, where did
the P come from to make ATP?
9 O-
H2O enolase H2O
C O
O
P is transferred Phosphoenolpyruvate
(PEP)
Phosphoenolpyruvate
(PEP)
C
CH2
P

from PEP to ADP ADP 10 ADP

O-

ükinase enzyme ATP

pyruvate kinase
ATP
C
C O
O

üADP ® ATP Pyruvate Pyruvate CH3

ATP
 Energy accounting of glycolysis
2 ATP 2 ADP

glucose ® ® ® ® ® pyruvate
6C 2x 3C

4 ADP 4 ATP

2 NAD+ 2

u Net gain = 2 ATP + 2 NADH

u some energy investment (-2 ATP)
u small energy return (4 ATP + 2 NADH)

u 1 6C sugar ® 2 3C sugars
 Is that all there is?
u Not a lot of energy…
u for 1 billon years+ this is how life on Earth survived
u no O2 = slow growth, slow reproduction
u only harvest 3.5% of energy stored in glucose
u more carbons to strip off = more energy to
harvest

O2 O2 glucose ® ® ® ® pyruvate
6C 2x 3C
O2
O2

O2
 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
8 + 2NADH

2-Phosphoglycerate 2-Phosphoglycerate
u Going to run out of NAD+ (2PG)
9
(2PG)

H2O H2O
u without regeneratingNAD+,
energy production would stop! Phosphoenolpyruvate
(PEP)
Phosphoenolpyruvate
(PEP)

ADP 10 ADP

ATP ATP

Pyruvate Pyruvate
 How is NADH recycled to NAD+?
with oxygen without oxygen
Another molecule aerobic respiration anaerobic respiration
must accept H from “fermentation”
pyruvate
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… fermentation
Fermentation (anaerobic)
u 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 NAD+
back to glycolysis®®
§ cheese, anaerobic exercise (no O2)
 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
 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
Three Stages of Catabolism
 Pyruvate is a branching point
Pyruvate

O2 O2

fermentation
anaerobic
respiration
mitochondria
Krebs cycle
aerobic respiration
 H+
H+ H+ H+
And how do we do that? H+ H+
H+ H+

u ATP synthase
u set up a H+ gradient
u allow H+ to flow
through ATP synthase
u powers bonding ADP + P
of Pi to ADP
ATP
H+
ADP + Pi ® ATP
Pentose Phosphate Pathway.
The Entner-Doudoroff Pathway
Cellular Respiration
Three Stages of Catabolism
To be continued…..