Energy of Life

Lecture 17 -18

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 Metabolism
The sum of the chemical processes that occur
in living organisms, resulting in growth,
production of energy, elimination of waste
material, etc.

• Anabolism- build up of complex molecules

• Catabolism- break down of complex

molecules
2
 Cellular Respiration
Harvesting Chemical Energy

ATP
4
 Harvesting stored energy
• Energy is stored in organic molecules (e.g.
carbohydrates, fats, proteins)
• Heterotrophs eat these organic molecules ® Food
– digest organic molecules to get…
• raw materials for synthesis
• fuels for energy
– controlled release of energy
– “burning” fuels in a series of step-by-step
enzyme-controlled reactions

5
Effect of insulin on glucose uptake and metabolism

Insulin binds to its receptor (1), which in turn starts many protein activation
cascades (2). These include: translocation of Glut-4 transporter to the plasma
membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and
fatty acid synthesis (6). It works at other sizes, but sometimes truncates the text
6
on the far right.
 Harvesting stored energy
• Glucose is the model
– catabolism of glucose to produce ATP
respiration

glucose + oxygen ® energy + water + carbondioxide

C6H12O6 + 6O2 ® ATP + 6H2O + 6CO2 + heat

combustion = making a lot of heat energy respiration = making ATP (& some heat)
by burning fuels in one step by burning fuels in many small steps
ATP
enzymes
ATP
O2
glucose
O2
fuel CO2 + H2O + heat CO2 + H2O + ATP (+ heat)
fuel
(carbohydrates) 7
 Overview of cellular respiration
• 4 metabolic stages
1. Glycolysis
-Anaerobic respiration
– respiration without O2
– in cytosol
– Aerobic respiration
– respiration using O2
– in mitochondria
2. Pyruvate oxidation
3. Krebs cycle
4. Electron transport chain

C6H12O6 + 6O2 ® ATP + 6H2O + 6CO2 (+ heat)

8
Cellular Respiration
Stage 1:
Glycolysis

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 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
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 Glycolysis summary
ENERGY INVESTMENT Endergonic
invest some ATP

G3P
ENERGY PAYOFF C-C-C-P Exergonic
harvest a little
4ATP
ATP & a little NADH

NET YIELD Yield

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

• G3P donates H ADP 7

phosphoglycerate
ADP
O-
kinase
• oxidize sugar ATP ATP C
3-Phosphoglycerate 3-Phosphoglycerate CHOH
• reduce NAD+ (3PG) (3PG) CH2 O P
• NAD+ ® NADH 8
O-
phosphoglyceromutase
– ATP production C O
2-Phosphoglycerate 2-Phosphoglycerate H C O P
• G3P ® pyruvate (2PG) (2PG) CH2OH

• PEP sugar donates P H2O

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enolase H2O
O-
C O
• ADP ® ATP C O P
Phosphoenolpyruvate Phosphoenolpyruvate
(PEP) (PEP) CH2

10 O-
ADP ADP
pyruvate kinase
Payola! ATP
C O
ATP
Finally some C O
ATP! Pyruvate Pyruvate CH3
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 Substrate-level Phosphorylation
• In the last steps of glycolysis, where did the P
come from to make ATP?
– the sugar substrate (PEP)
9 O-
H2O enolase H2O
C O
O
P is transferred from Phosphoenolpyruvate
(PEP)
Phosphoenolpyruvate
(PEP)
C
CH2
P

PEP to ADP ADP 10 ADP

O-

" kinase enzyme ATP

pyruvate kinase
ATP
C
C O
O

" ADP ® ATP Pyruvate Pyruvate CH3

ATP

I get it!
The PO4 came
directly from
the substrate!
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 Energy accounting of glycolysis
2 ATP 2 ADP

glucose ® ® ® ® ® pyruvate
6C 2x 3C

4 ADP 4 ATP
• Net gain = 2 ATP
– some energy investment (-2 ATP)
– small energy return (+4 ATP)
• 1 molecule of 6C sugar ® 2 molecules of 3C sugars

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 How is NADH recycled to NAD+?
with oxygen without oxygen
Another molecule aerobic respiration anaerobic respiration
must accept H from fermentation
pyruvate
NADH
H2 O NAD+
CO2

O2 NADH NADH acetaldehyde

Recycle acetyl-CoA NAD+

NADH
NADH
lactate NAD+

(lactic acid)

which path you Krebs

ethanol
use depends on cycle

who you are… 22

Fermentation (anaerobic)
• Bacteria, yeast
pyruvate ® ethanol + CO2
3C 2C 1C
NADH NAD+
to glycolysis®®
" beer, wine, bread

" Animals, some fungi

pyruvate ® lactic acid
3C 3C
NADH NAD+
to glycolysis®®
" cheese, anaerobic exercise (no O2) 23
 Alcohol Fermentation bacteria yeast

pyruvate ® ethanol + CO2

3C 2C 1C
NADH NAD+

" Dead end process

" at ~12% ethanol, kills
yeast
" can’t reverse the
reaction

Count the
carbons!

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 Lactic Acid Fermentation
O2 animals
pyruvate ® lactic acid
®
3C 3C
NADH NAD+

" Reversible process

" once O2 is available,
lactate is converted
back to pyruvate by
the liver

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 Pyruvate is a branching point
Pyruvate

O2 O2

fermentation
anaerobic
respiration
In mitochondria
Kreb’s cycle
aerobic respiration
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Cellular Respiration
Stage 2 & 3:
Oxidation of Pyruvate
Krebs Cycle

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 Glycolysis is only the start
• Glycolysis
glucose ® ® ® ® ® pyruvate
6C 2x 3C

• Pyruvate has more energy to yield

– if O2 is available, pyruvate enters mitochondria
– enzymes of Krebs cycle complete the full
oxidation of sugar to CO2

pyruvate ® ® ® ® ® ® CO2
3C 1C
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Cellular respiration

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 Mitochondria — Structure
• Double membrane energy harvesting organelle
– smooth outer membrane
– highly folded inner membrane
• cristae
– intermembrane space
• fluid-filled space between membranes
– matrix
• inner fluid-filled space
– DNA, ribosomes outer
intermembrane membrane
– enzymes space inner
membrane
cristae
matrix

What cells would have a mitochondrial

lot of mitochondria? DNA 31
 Oxidation of pyruvate
• Pyruvate enters mitochondria

[
2x pyruvate ® ® ® acetyl CoA + CO2
3C
NAD
2C 1C ]
Where
– 3 step oxidation process does the
CO2 go?
– releases 1 CO2 (count the carbons!) Exhale!

– reduces 2 NAD ® 2 NADH (moves e-)

– produces acetyl CoA
• Acetyl CoA enters Krebs cycle
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Pyruvate oxidized to Acetyl CoA

NAD+ reduction

Coenzyme A Acetyl CoA

Pyruvate
CO2 C-C
C-C-C oxidation

2x [ Yield = 2C product + NADH + CO ] 2 34

 Krebs cycle 1937 | 1953

• Citric Acid Cycle

– in mitochondrial matrix
– 8 step pathway
• each catalyzed by specific enzyme Hans Krebs
1900-1981
• step-wise catabolism of 6C citrate molecule
• Evolved later than glycolysis
– does that make evolutionary sense?
• bacteria ®3.5 billion years ago (glycolysis)
• free O2 ®2.7 billion years ago (photosynthesis)
• eukaryotes ®1.5 billion years ago (aerobic
respiration = organelles ® mitochondria)
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Count the electron carriers!
CO2
pyruvate acetyl CoA
3C 2C
NADH
citrate
NADH 4C 6C

This happens 4C x2 6C
twice for each reduction CO2
glucose of electron
molecule carriers NADH
4C 5C

FADH2 CO2
4C 4C NADH
ATP
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Electron Carriers = Hydrogen Carriers

" Krebs cycle

produces large
quantities of
electron carriers
! NADH
! FADH2

! go to Electron
Transport Chain

Why electron
carriers are so
important?

37
 Energy accounting of Krebs cycle

4 NAD + 1 FAD 4 NADH + 1 FADH2

2x pyruvate ® ® ® ® ® ® ® ® ® CO2
3C 3x 1C
1 ADP 1 ATP
ATP

Net gain = 2 ATP

= 8 NADH + 2 FADH2
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Cellular Respiration
Stage 4:
Electron Transport Chain

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 Mitochondria
• Double membrane
– outer membrane
– inner membrane
• highly folded cristae
• enzymes & transport proteins
– intermembrane space
• fluid-filled space between membranes
outer
intermembrane membrane
space inner
membrane
cristae
matrix

41
 ATP accounting so far…
• Glycolysis ® 2 ATP
• Kreb’s cycle ® 2 ATP
• Life takes a lot of energy to run, need to
extract more energy than 4 ATP!
There should be a better way!

A working muscle recycles over 10

million ATPs per second 42
 There is a better way!
• Electron Transport Chain
– series of molecules built into inner
mitochondrial membrane
• along cristae
• transport proteins & enzymes
– transport of electrons down ETC linked to
pumping of H+ to create H+ gradient
– yields ~34 ATP from 1 glucose!
– only in presence of O2 (aerobic respiration)

43
Electron Transport Chain
Inner
mitochondrial
Intermembrane space membrane

C
Q

NADH cytochrome cytochrome c

dehydrogenase bc complex oxidase complex
Mitochondrial matrix

44
 Electron Transport Chain
NADH ® NAD+ + H Building proton gradient!
e intermembrane
space
P
H+ H+ H+
inner
mitochondrial
H ® e- + H+ C membrane

Q e–
e– H e–
FADH2
FAD
H 1
NADH 2H+ + O2 H2O
NAD+ 2
NADH cytochrome cytochrome c
dehydrogenase bc complex oxidase complex
mitochondrial
matrix

What powers the proton (H+) pumps?…

46
 But what “pulls” the
electrons down the ETC?

O2

electrons
flow downhill
to O2 oxidative phosphorylation 48
 Electrons flow down hill
• Electrons move in steps from
carrier to carrier downhill to O2
– each carrier more electronegative
– controlled oxidation
– controlled release of energy

make ATP
instead of
fire!

49
ETC of Respiration

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Cellular respiration ~ 40
ATP

2 ATP + ~2 ATP + 2 ATP + ~34 ATP

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 Enzymes:

“Helper” Protein molecules

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 Chemical reactions of life
• Processes of life
– building molecules
• synthesis +
– breaking down molecules
• digestion +

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 Enzymes
• A protein catalyst
• Enzymes are important proteins found in living
things. An enzyme is a protein that changes the
rate of a chemical reaction.
They speed metabolic reactions.
• Each enzyme is the specific helper to
a specific reaction
– each enzyme needs to be the right shape for the job
– enzymes are named for the reaction
they help
• sucrase breaks down sucrose
• proteases breakdown proteins
• lipases breakdown lipids
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• DNA polymerase builds DNA
 Enzymes aren’t used up
• Enzymes are not changed by the reaction
– used only temporarily
– re-used again for the same reaction with other
molecules
– very little enzyme needed to help in many
reactions

substrate product

active site enzyme

57
 Enzyme vocabulary
• Enzyme
– helper protein molecule
• Substrate
– molecule that enzymes work on
• Products
– what the enzyme helps produce from the
reaction
• Active site
– part of enzyme
that substrate
molecule fits into
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 What affects enzyme action
• Correct protein structure
– correct order of amino acids
– why? enzyme has to be right shape
• Temperature
– why? enzyme has to be right shape
• pH (acids & bases)
– why? enzyme has to be right shape

59
 Temperature
• Effect on rates of enzyme activity
– Optimum temperature
• human enzymes
–35°- 40°C (body temp = 37°C)

– Raise temperature (boiling)

• denature protein = unfold = lose
shape

– Lower temperature T°
• molecules move slower
61
 Temperature
human What’s
enzymes happening
here?!
reaction rate

37°
temperature

62
 pH
• Effect on rates of enzyme activity
– changes in pH changes protein shape~
Denatures
– most human enzymes = pH 6-8
• depends on where in body
• pepsin (stomach) = pH 3
• trypsin (small intestines) = pH 8

63
 pH
stomach intestines What’s
happening
pepsin trypsin here?!
reaction rate

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
pH

64
 Classification of Enzyme:

Enzymes are protein. There are 6 types of reaction

they can catalyze-

• Oxidoreductases: These catalyze oxidation and

reduction reactions.
• Transferases: These catalyze the transfer of a
chemical group from one compound to another.
• Hydrolases: These catalyze hydrolysis (splitting
by use of water) reactions. Most digestive enzymes
are hydrolases.
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Classification of Enzyme (Cont.)
* Lyases: these catalyze the breakdown of molecules
by reactions that do not involved hydrolysis.

• Isomerases: These catlyze the transformation of

one isomer into another

• Ligases: These catalyze the formation of bonds

between compounds, often using the free energy made
available from ATP hydrolysis.

To remember from the acronym: OTHLIL

66
 Photosynthesis:
Life from Light and Air

67
Energy needs of life
– Heterotrophs
• consumers
• animals
• fungi
• most bacteria

– Autotrophs
• producers
• plants
• photosynthetic bacteria
(blue-green algae)
69
 How are they connected?
Heterotrophs
making energy & organic molecules from ingesting organic molecules

glucose + oxygen ® carbon + water + energy

dioxide
C6H12O6 + 6O2 ® 6CO2 + 6H2O + ATP
exergonic
Autotrophs
making energy & organic molecules from light energy

carbon + water + energy ® glucose + oxygen

dioxide
6CO2 + 6H2O +light ® C6H12O6 + 6O2
energy
endergonic 70
 Energy cycle
sun

Photosynthesis
plants

CO2 H2O glucose O2

animals, plants
Cellular Respiration

The Great Circle

of Life,Mufasa!
ATP
71
Plant structure
• Obtaining raw materials
– sunlight
• leaves = solar collectors
– CO2
• stomates = gas exchange
– H2O
• uptake from roots
– nutrients
• N, P, K, S, Mg, Fe…
• uptake from roots

73
Plant structure
• Chloroplasts
– double membrane
– stroma
• fluid-filled interior
– thylakoid sacs
– grana stacks

• Thylakoid membrane
contains
– chlorophyll molecules
– electron transport chain
– ATP synthase
+ H+ H H+
+
• H+ gradient built up within H+ H+ H
H + H+ H+ H+
thylakoid sac H +

76
Photosynthesis

• Light reactions
– light-dependent reactions
– energy production reactions
• convert solar energy to chemical energy
• ATP & NADPH
• Calvin cycle
– light-independent reactions
– sugar production reactions
• uses chemical energy (ATP & NADPH) to
reduce CO2 & synthesize C6H12O6 77
 Light Reactions
H2O + light ® ATP + NADPH + O2
energy

H2 O
sunlight
" produces ATP
" produces NADPH
" releases O2 as a
Energy Building
waste product
Reactions
NADPH

ATP

O2 78
 Calvin Cycle

CO2 + ATP + NADPH ® C6H12O6 + ADP + NADP

CO2 " builds sugars

" uses ATP &
ADP
NADPH
NADP Sugar " recycles ADP &
Building
Reactions
NADP back to
NADPH make more
ATP ATP & NADPH

sugars 79
C6H12O6
 Putting it all together
light
CO2 + H2O + energy ® C6H12O6 + O2

sunlight
H2 O CO2
Plants make both:
" energy
ADP
"ATP & NADPH
Energy NADP Sugar " sugars
Building Building
Reactions Reactions
NADPH

ATP

sugars 80
O2 C6H12O6
 " Chloroplasts transform light
ETC of Photosynthesis energy into chemical energy of
ATP
! use electron carrier NADPH

81
Thank You

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