1. Cellular Respiration Harvesting Chemical Energy

2. Harvesting stored energy
Energy is stored in organic molecules
heterotrophs eat food (organic molecules)
digest organic molecules
serve as raw materials for building & fuels for energy
controlled release of energy
series of step-by-step enzyme-controlled reactions
“burning” fuels
carbohydrates, lipids, proteins
We eat to take in the fuels to make ATP which will then be used to help us build biomolecules and grow and move and… live!
heterotrophs = “fed by others”
vs.
autotrophs = “self-feeders”

3. Harvesting energy stored in glucose
Glucose is the ideal molecule
catabolism of glucose to produce ATP
glucose + oxygen  carbon + water + energy
dioxide
C6H12O6
6O2
6CO2
6H2O
ATP  +
+ heat
respiration
Movement of hydrogen atoms from glucose to water
combustion = making heat energy by burning fuels in one step
respiration = making ATP (& less heat) by burning fuels in many small steps
ATP
fuel (carbohydrates)
CO2 + H2O + heat
CO2 + H2O + ATP (+ heat)

4. How do we harvest energy from fuels?
Digest large molecules into smaller ones
break bonds & move electrons from one molecule to another
as electrons move they carry energy with them
that energy is stored in another bond, released as heat, or harvested to make ATP
They are called oxidation reactions because it reflects the fact that in biological systems oxygen, which attracts electrons strongly, is the most common electron acceptor.
Oxidation & reduction reactions always occur together therefore they are referred to as “redox reactions”.
As electrons move from one atom to another they move farther away from the nucleus of the atom and therefore are at a higher potential energy state.
The reduced form of a molecule has a higher level of energy than the oxidized form of a molecule. The ability to store energy in molecules by transferring electrons to them is called reducing power, and is a basic property of living systems.
loses e-
gains e-
oxidized
reduced + – + + e-
oxidation
reduction e-

5. How do we move electrons in biology?
Moving electrons
in living systems, electrons do not move alone
electrons move as part of H atom
loses e-
gains e-
oxidized
reduced + – + + H
Energy is transferred from one molecule to another via redox reactions.
C6H12O6 has been oxidized fully == each of the carbons (C) has been cleaved off and all of the hyrogens (H) have been stripped off & transferred to oxygen (O) — the most electronegative atom in livng systems. This converts O2 into H2O as it is reduced.
The reduced form of a molecule has a higher energy state than the oxidized form. The ability of organisms to store energy in molecules by transferring electrons to them is referred to as reducing power. The reduced form of a molecule in a biological system is the molecule which has gained a H atom, hence NAD+  NADH once reduced.
soon we will meet the electron carriers NAD & FADH = when they are reduced they now have energy stored in them that can be used to do work.
oxidation
reduction H
C6H12O6
6O2
6CO2
6H2O
ATP  +
oxidation
reduction H

6. Moving electrons in respiration
Electron carriers move electrons by shuttling H atoms around
NAD+  NADH (reduced)
FAD+2  FADH2 (reduced)
reducing power!
NAD+
nicotinamide
Vitamin B3 P O– O –O C
NH2 N+ H
NADH P O– O –O C
NH2 N+ H
adenine
ribose sugar
phosphates + H
reduction
Nicotinamide adenine dinucleotide (NAD) — and its relative nicotinamide adenine dinucleotide phosphate (NADP) which you will meet in photosynthesis — are two of the most important coenzymes in the cell.
In cells, most oxidations are accomplished by the removal of hydrogen atoms. Both of these coenzymes play crucial roles in this.
Nicotinamide is also known as Vitamin B3 is believed to cause improvements in energy production due to its role as a precursor of NAD (nicotinamide adenosine dinucleotide), an important molecule involved in energy metabolism. Increasing nicotinamide concentrations increase the available NAD molecules that can take part in energy metabolism, thus increasing the amount of energy available in the cell.
Vitamin B3 can be found in various meats, peanuts, and sunflower seeds. Nicotinamide is the biologically active form of niacin (also known as nicotinic acid).
FAD is built from riboflavin — also known as Vitamin B2. Riboflavin is a water-soluble vitamin that is found naturally in organ meats (liver, kidney, and heart) and certain plants such as almonds, mushrooms, whole grain, soybeans, and green leafy vegetables. FAD is a coenzyme critical for the metabolism of carbohydrates, fats, and proteins into energy.
oxidation
stores energy as a reduced molecule

7. Coupling oxidation & reduction
Redox reactions in respiration
release energy as breakdown molecules
break C-C bonds
strip off electrons from C-H bonds by removing H atoms
C6H12O6  CO2 = fuel has been oxidized
electrons attracted to more electronegative atoms
in biology, the most electronegative atom?
O2  H2O = oxygen has been reduced
release energy to synthesize ATP
 O2
O2 is 2 oxygen atoms both looking for electrons
LIGHT FIRE ==> oxidation
RELEASING ENERGY
But too fast for a biological system
C6H12O6
6O2
6CO2
6H2O
ATP  +
oxidation
reduction

8. Oxidation & reduction Reduction Oxidation  removing O adding O
removing H
loss of electrons
releases energy
exergonic
Reduction
removing O
adding H
gain of electrons
stores energy
endergonic
C6H12O6
6O2
6CO2
6H2O
ATP  +
oxidation
reduction
During cellular respiration, the fuel (such as glucose) is oxidized,
and O2 is reduced

9. The Stages of Cellular Respiration: A Preview
Cellular respiration has three stages:
Glycolysis (breaks down glucose into two molecules of pyruvate)
The citric acid cycle (completes the breakdown of glucose)
Oxidative phosphorylation (accounts for most of the ATP synthesis)
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10. glucose      pyruvate
Stage 1: Glycolysis
Breaking down glucose
“glyco – lysis” (splitting sugar)
most ancient form of energy capture
starting point for all cellular respiration
inefficient
generate only 2 ATP for every 1 glucose
in cytosol
why does that make evolutionary sense?
glucose      pyruvate 6C 2x 3C
Life on Earth first evolved without free oxygen (O2) in atmosphere
energy had to be captured from organic molecules in absence of O2
Organisms that evolved glycolysis are ancestors of all modern life
all organisms still utilize glycolysis

11. Stage 1: Glycolysis
METABOLIC PATHWAY
2 Pyruvate
Glucose 30 11

14. Stage 1: Glycolysis Forms ATP through substrate level phosphorylation
An ENZYME transfers a phosphate group from a substrate to ADP
Enzyme
Enzyme
ADP P
Substrate
ATP
Product

15. Glycolysis summary invest some ATP harvest a little more ATP
& a little NADH
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.
P is transferred from PEP to ADP
kinase enzyme
ADP  ATP

16. Most of that energy remains stored in the two molecules of pyruvate
Glycolysis releases less than ¼ of the chemical energy stored in glucose.
Most of that energy remains stored in the two molecules of pyruvate
If O2 is present, pyruvate enters a mitochondrion (eukaryote; if prokaryote, occurs in cytosol)

17. Pyruvate is a branching point
fermentation
Kreb’s cycle
mitochondria

18. Oxidation of Pyruvate
Pyruvate’s carboxyl group released as a molecule of CO2
Remaining 2 C molecule is oxidized forming acetate and NADH
Coenzyme A attaches to acetate by an unstable bond (reactive with stored PE)

19. Pyruvate oxidized to Acetyl CoA
reduction
Release CO2 because completely oxidized…already released all energy it can release … no longer valuable to cell….
Because what’s the point?
The Point is to make ATP!!!
oxidation
Yield = 2C sugar + CO2 + NADH

20. Step 2: The Citric Acid Cycle
The citric acid cycle, also called the Krebs cycle, takes place within the mitochondrial matrix
The cycle oxidizes organic fuel derived from pyruvate, generating 1 ATP, 3 NADH, and 1 FADH2 per turn
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21. Pyruvate CO2 NAD+ CoA NADH + H+ Acetyl CoA CoA CoA Citric acid cycle 2
Fig. 9-11
Pyruvate
CO2
NAD+
CoA
NADH
+ H+
Acetyl CoA
CoA
CoA
Citric
acid
cycle 2
CO2
Figure 9.11 An overview of the citric acid cycle
FADH2
3 NAD+
FAD 3
NADH
+ 3 H+
ADP + P i
ATP

22. The citric acid cycle has eight steps, each catalyzed by a specific enzyme
The acetyl group of acetyl CoA joins the cycle by combining with oxaloacetate, forming citrate
The next seven steps decompose the citrate back to oxaloacetate, making the process a cycle
The NADH and FADH2 produced by the cycle relay electrons extracted from food to the electron transport chain
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23. reduction of electron carriers
Count the carbons & electron carriers!
pyruvate 3C 2C
acetyl CoA
citrate 4C 6C
NADH x2 4C 6C
This happens twice for each glucose molecule
CO2
reduction of electron carriers
NADH 5C 4C
CO2
FADH2 4C 4C
NADH
ATP

24. What’s so important about NADH?
NADH & FADH2
Krebs cycle produces:
8 NADH
2 FADH2
2 ATP
Let’s go to ETC…
What’s so important about NADH?

25. So why the Krebs cycle? If the yield is only 2 ATP, then why?
value of NADH & FADH2
electron carriers
reduced molecules store energy!
to be used in the Electron Transport Chain

26. 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!
Why stop here…
There’s got
to be more to
life than this.

27. Step 3: Oxidative Phosphorylation
Electron Transport Chain
series of molecules built into inner mitochondrial membrane
mostly transport (integral) proteins
transport of electrons down ETC linked to ATP synthesis
yields ~28 ATP from 1 glucose!
only in presence of O2 (aerobic)
That sounds more like it!

28. Don’t forget the Mito! Double membrane * form fits function!
outer membrane
inner membrane (ETC here!)
highly folded cristae*
fluid-filled space between membranes = intermembrane space
Matrix (Kreb’s here!)
central fluid-filled space
* form fits function!

29. Remember the electron carriers?
Kreb’s cycle
Glycolysis
PGAL
8 NADH
2 FADH2
2 NADH

30. Electron Transport Chain
NADH and FADH2 passes electrons to ETC
H cleaved off NADH & FADH2
electrons stripped from H atoms  H+ (H ions)
electrons passed from one electron carrier to next in mitochondrial membrane (ETC)
transport proteins in membrane pump H+ across inner membrane to intermembrane space
Oxidation refers to the loss of electrons to any electron acceptor, not just to oxygen.
Uses exergonic flow of electrons through ETC to pump H+ across membrane.

31. The Pathway of Electron Transport
The electron transport chain is in the cristae of the mitochondrion
Most of the chain’s components are proteins, which exist in multiprotein complexes
The carriers alternate reduced and oxidized states as they accept and donate electrons
Electrons drop in free energy as they go down the chain and are finally passed to O2, forming H2O (H+ picked up from the aqueous solution)
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32. Electrons flow downhill
Electrons move in steps from carrier to carrier downhill to O2
each carrier more electronegative
controlled oxidation
controlled release of energy
Electrons move from molecule to molecule until they combine with O & H ions to form H2O
It’s like pumping water behind a dam -- if released, it can do work

33. Electrons are passed through a number of proteins to O2
Electrons are transferred from NADH or FADH2 to the electron transport chain
Electrons are passed through a number of proteins to O2
The electron transport chain generates no ATP
The chain’s function is to break the large free-energy drop from food to O2 into smaller steps that release energy in manageable amounts
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34. Chemiosmosis: The Energy-Coupling Mechanism
Electron transfer in the electron transport chain causes proteins to pump H+ from the mitochondrial matrix to the intermembrane space
H+ then moves back across the membrane, passing through channels in ATP synthase
ATP synthase uses the exergonic flow of H+ to drive phosphorylation of ATP
This is an example of chemiosmosis, the use of energy in a H+ gradient to drive cellular work
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35. Why the build up H+? ATP synthase ADP + Pi  ATP
enzyme in inner membrane of mitochondria
ADP + Pi  ATP
only channel permeable to H+
H+ flow down concentration gradient = provides energy for ATP synthesis
molecular power generator!
flow like water over water wheel
flowing H+ cause change in shape of ATP synthase enzyme
powers bonding of Pi to ADP
“proton-motive” force

36. Oxidative Phosphorylation
ATP synthesis
powered by redox
reactions of ETC

37. Cellular respiration

38. Summary of cellular respiration
C6H12O6
6O2
6CO2
6H2O
~32 ATP  +
Where did the glucose come from?
Where did the O2 come from?
Where did the CO2 come from?
Where did the H2O come from?
Where did the ATP come from?
What else is produced that is not listed in this equation?
Why do we breathe?
Where did the glucose come from?
from food eaten
Where did the O2 come from?
breathed in
Where did the CO2 come from?
oxidized carbons cleaved off of the sugars
Where did the H2O come from?
from O2 after it accepts electrons in ETC
Where did the ATP come from?
mostly from ETC
What else is produced that is not listed in this equation?
NAD, FAD, heat!

39. Taking it beyond…
What is the final electron acceptor in electron transport chain? O2
So what happens if O2 unavailable?
ETC backs up
ATP production ceases
cells run out of energy
and you die!
What if you have a chemical that punches holes in the inner mitochondrial membrane?

40. 9.5: Fermentation and anaerobic respiration
Most cellular respiration requires O2 to produce ATP
Glycolysis can produce ATP with or without O2 (in aerobic or anaerobic conditions)
In the absence of O2, glycolysis couples with fermentation or anaerobic respiration to produce ATP
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41. Anaerobic Respiration
An electron transport chain with a final electron acceptor OTHER THAN O2 is present
Ex: methanogens are archaebacteria that reduce CO2 to methane to regenerate NAD+ from NADH

42. Types of Fermentation
Fermentation consists of glycolysis plus reactions that regenerate NAD+, which can be reused by glycolysis
Two common types are alcohol fermentation and lactic acid fermentation
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43. In alcohol fermentation, pyruvate is converted to ethanol in two steps, with the first releasing CO2
Alcohol fermentation by yeast is used in brewing, winemaking, and baking
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44. (a) Alcohol fermentation
Fig. 9-18a
2 ADP + 2 P
2 ATP i
Glucose
Glycolysis
2 Pyruvate
2 NAD+
2 NADH 2
CO2
+ 2 H+
Figure 9.18a Fermentation
2 Acetaldehyde
2 Ethanol
(a) Alcohol fermentation

45. In lactic acid fermentation, pyruvate is reduced to NADH, forming lactate as an end product, with no release of CO2
Lactic acid fermentation by some fungi and bacteria is used to make cheese and yogurt
Human muscle cells use lactic acid fermentation to generate ATP when O2 is scarce
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46. (b) Lactic acid fermentation
Fig. 9-18b
2 ADP + 2 P
2 ATP i
Glucose
Glycolysis
2 NAD+
2 NADH
+ 2 H+
2 Pyruvate
Figure 9.18b Fermentation
2 Lactate
(b) Lactic acid fermentation

47. Fermentation Bacteria, yeast pyruvate  ethanol + CO2
NADH
NAD+
beer, wine, bread
at ~12% ethanol, kills yeast
Animals, some fungi
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.
pyruvate  lactic acid 3C
NADH
NAD+
cheese, yogurt, anaerobic exercise (no O2)

48. The Versatility of Catabolism
Catabolic pathways funnel electrons from many kinds of organic molecules into cellular respiration
Glycolysis accepts a wide range of carbohydrates
Proteins must be digested to amino acids; amino groups can feed glycolysis or the citric acid cycle
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49. Fats are digested to glycerol (used in glycolysis) and fatty acids (used in generating acetyl CoA)
An oxidized gram of fat produces more than twice as much ATP as an oxidized gram of carbohydrate
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50. Citric acid cycle Oxidative phosphorylation
Fig. 9-20
Proteins
Carbohydrates
Fats
Amino
acids
Sugars
Glycerol
Fatty
acids
Glycolysis
Glucose
Glyceraldehyde-3- P
NH3
Pyruvate
Acetyl CoA
Figure 9.20 The catabolism of various molecules from food
Citric
acid
cycle
Oxidative
phosphorylation

51. Biosynthesis (Anabolic Pathways)
The body uses small molecules to build other substances
These small molecules may come directly from food, from glycolysis, or from the citric acid cycle
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52. Regulation of Cellular Respiration via Feedback Mechanisms
Feedback inhibition is the most common mechanism for control
If ATP concentration begins to drop, respiration speeds up; when there is plenty of ATP, respiration slows down
Control of catabolism is based mainly on regulating the activity of enzymes at strategic points in the catabolic pathway
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