1. Cellular Respiration

2. Cellular Respiration
Conversion of stored energy in biological molecules into ATP for cellular work - produces carbon dioxide and usually requires oxygen
HOW: Gradual release of energy through a series of steps – slower release allows for a more efficient capture of the energy

3. (a) Uncontrolled reaction
Free energy, G
H2O
Explosive release of heat and light energy
H2 + 1/2 O2

4. Electron transport chain (b) Cellular respiration
(from food via NADH)
2 H e–
2 H+
2 e–
H2O
Controlled release of energy for synthesis of ATP
ATP
Electron transport chain
Free energy, G
(b) Cellular respiration +
Figure 9.5 B

5. Overall Reaction
C6H12O6 + 6 O2  6 CO2 + 6 H2O

6. Mechanisms of Cellular Respiration
Transfer of electrons from a higher energy state (glucose) to a lower energy state (Water) through Oxidation-reduction reactions (REDOX)
REDOX reactions:
- transfer of electrons from one substance (reducing agent) to another (oxidzing agent)
- result: reducing agent becomes more positive (Oxidized) and the oxidizing agent becomes more negative (REDUCED in charge)

7. NAD+ - nicotinamide adenine dinucleotide
IMPORTANCE OF HYDROGEN ACCEPTORS chemicals that accept hydrogens from molecules and transfer them for other reactions
NAD+ - nicotinamide adenine dinucleotide
FAD - flavin adenine dinucleotide
- allow for the gradual controlled release of energy

8. NAD+ H O O– + (from food) Dehydrogenase Reduction of NAD+P
CH2 HO OH N+ C
NH2 N
Nicotinamide (oxidized form) +
2[H]
(from food)
Dehydrogenase
Reduction of NAD+
Oxidation of NADH
2 e– + 2 H+
2 e– + H+
NADH
Nicotinamide (reduced form)
Figure 9.4

10. TYPES of Cellular respiraton
Aerobic - uses oxygen - most efficient
- generates ATP per glucose
Anaerobic - (AKA fermentation) does not use oxygen - less efficient
generates about 2 ATP

11. Aerobic cellular respiration occurs in the mitochondria
Structure of the mitochondria
Outer membrane
Inner membrane
Intermembranous space
Matrix

12. Oxidative phosphorylation: electron transport and chemiosmosis
Electrons
carried
via NADH
Glycolsis
Glucose
Pyruvate
ATP
Substrate-level
phosphorylation
Electrons carried
via NADH and
FADH2
Citric acid cycle
Oxidative phosphorylation: electron transport and chemiosmosis
Oxidative
Mitochondrion
Cytosol

13. STEPS OF CELLULAR RESPIRATION
1. Glycolysis - splitting of sugar - in cytoplasm
REACTANTS:
Glucose (C6H12O6)
ATP
NAD+ (nicotinamide adenine dinucleotide)
PRODUCTS:
2 Pyruvate (3 carbon sugars)
4 ATP (really 2 net ATP)
NADH (reduced NAD+)

14. STEPS OF CELLULAR RESPIRATION
2. Kreb's Cycle - matrix of mitochondria
PRODUCTS
CO2
ATP
NADH
FADH2
REACTANTS:
Pyruvate (sort of)
ADP + P
NAD+
FAD

15. STEPS OF CELLULAR RESPIRATION
3. Electron transport chain
- innermembrane
- intermembranous space
REACTANTS:
NADH
FADH2 O2
ADP + P
PRODUCTS:
NAD+
FAD
H2O
ATP - lots

16. GLYCOLYSIS - splitting of sugar
6 carbon sugar split into 2, 3 carbon compounds to be made into PYRUVATE
10 steps in the cytosol of the cell broken into 2 parts:
1. Energy-Investment Phase: 2 ATP USED
2. Energy-Payoff Phase: 4 ATP and 2 NADH generated
SUBSTRATE LEVEL PHOSPHORYLATION
– transfer of phosphates from a molecule to ADP using an enzyme

17. Figure 9.7
Enzyme
ATP
ADP
Product
Substrate P +

18. Energy investment phase
Glycolysis
Citric acid cycle
Oxidative phosphorylation
ATP
2 ATP
4 ATP
used
formed
Glucose
2 ATP + 2 P
4 ADP + 4
2 NAD+ + 4 e- + 4 H +
2 NADH
+ 2 H+
2 Pyruvate + 2 H2O
Energy investment phase
Energy payoff phase
4 ATP formed – 2 ATP used
2 NAD+ + 4 e– + 4 H +

19. Phosphoglucoisomerase
Dihydroxyacetone
phosphate
Glyceraldehyde-
3-phosphate H OH HO
CH2OH O P
CH2O
CH2 C
CHOH
ATP
ADP
Hexokinase
Glucose
Glucose-6-phosphate
Fructose-6-phosphate
Phosphoglucoisomerase
Phosphofructokinase
Fructose-
1, 6-bisphosphate
Aldolase
Isomerase
Glycolysis 1 2 3 4 5
Oxidative
phosphorylation
Citric
acid
cycle

20. 1, 3-Bisphosphoglycerate
2 NAD+
NADH 2
+ 2 H+
Triose phosphate
dehydrogenase
P i P C
CHOH O
CH2 O–
1, 3-Bisphosphoglycerate
2 ADP
2 ATP
Phosphoglycerokinase
3-Phosphoglycerate
Phosphoglyceromutase
CH2OH H
2-Phosphoglycerate
2 H2O
Enolase
Phosphoenolpyruvate
Pyruvate kinase
CH3 6 8 7 9 10
Pyruvate

21. ENERGY SUMMARY 2 ATP used 4 ATP and 2 NADH generated
Yields 2 ATP and 2 NADH per glucose

22. Transport across Mitochondrial Membrane
Prepping for Kreb’s: changing pyruvate to acetyl Co-A
Pyruvate enters mitochondria and a carboxy group is removed producing CO2 - go from a 3 carbon to a 2 carbon
2 carbon compound loses a Hydrogen to NAD+ to make NADH and acetate
NADH goes to ETC
Acetate bonds with coenzyme A to make acetyl-CoA

23. CYTOSOL MITOCHONDRION Pyruvate Acetyle CoA
NADH
+ H+
NAD+ 2 3 1
CO2
Coenzyme A
Pyruvate
Acetyle CoA S
CoA C
CH3 O
Transport protein O–

24. KREB’S CYCLE EACH GLUCOSE TURNS THE CYCLE TWICE
Where: Matrix of mitochondria
2 remaining Carbons go through the cycle producing 2 CO2
Process Generates Per acetyl - CoA:
3 NADH
1 FADH2
1 ATP
X 2 = 6 NADH, 2 FADH2, 2 ATP per glucose
EACH GLUCOSE TURNS THE CYCLE TWICE
NADH and FADH2 go to ETC

25. Oxidative phosphorylation
ATP
2 CO2
3 NAD+
3 NADH
+ 3 H+
ADP + P i
FAD
FADH2
Citric acid cycle
CoA
Acetyle CoA
NADH
CO2
Pyruvate (from glycolysis, 2 molecules per glucose)
Glycolysis
Oxidative phosphorylation

26. Acetyl CoA Oxaloacetate Malate Citrate Isocitrate Citric acid cycle
NADH
Oxaloacetate
Citrate
Malate
Fumarate
Succinate
Succinyl
CoA
a-Ketoglutarate
Isocitrate
Citric
acid
cycle S SH
FADH2
FAD
GTP
GDP
NAD+
ADP
P i
CO2
H2O
+ H+ C
CH3 O
COO–
CH2 HO HC CH 1 2 3 4 5 6 7 8
Glycolysis
Oxidative
phosphorylation
ATP

28. ELECTRON TRANSPORT CHAIN
- generates a proton gradient to drive oxidative phosphorylation (chemiosmosis)
LOCATION:
matrix: inner membrane: intermembranous space
Inner membrane:
Chain of proteins complexes that move electrons through membrane by redox reactions
Each transfer from one complex to another lowers the energy of the electron
Energy is used to pump H+ from the matrix to the intermembranous space
BUILDS PROTON GRADIENT

29. Free energy (G) relative to O2 (kcl/mol)
H2O O2
NADH
FADH2
FMN
Fe•S O
FAD
Cyt b
Cyt c1
Cyt c
Cyt a
Cyt a3
2 H + + 12 I II
III IV
Multiprotein complexes 10 20 30 40 50
Free energy (G) relative to O2 (kcl/mol)

30. NADH breaks into NAD+ and H+ and electrons
electrons go into electron transport chain –
FADH2 deposits electrons further down chain
At specific points H+ are pumped across the membrane - NAD+ is reused
Each NADH gives enough energy for the production of 3 ATP
Each FADH2 gives enough energy for the production of 2 ATP

31. Electron transport chain Oxidative phosphorylation
and chemiosmosis
Glycolysis
ATP
Inner
Mitochondrial
membrane H+
P i
Protein complex
of electron
carners
Cyt c I II
III IV
(Carrying electrons
from, food)
NADH
FADH2
NAD+
FAD+
2 H+ + 1/2 O2
H2O
ADP +
Electron transport chain
Electron transport and pumping of protons (H+),
which create an H+ gradient across the membrane
Chemiosmosis
ATP synthesis powered by the flow
Of H+ back across the membrane
synthase Q
Oxidative phosphorylation
Intermembrane
space
mitochondrial
matrix

32. H+s pumping builds PROTON-MOTIVE FORCE or CHEMIOSMOTIC GRADIENT
protons diffuse back across to other side through a protein (facilitated diffusion)  ATP synthase
cylidrical rotor
knob with a rod in the rotor

33. Electron transport chain Oxidative phosphorylation
and chemiosmosis
Glycolysis
ATP
Inner
Mitochondrial
membrane H+
P i
Protein complex
of electron
carners
Cyt c I II
III IV
(Carrying electrons
from, food)
NADH
FADH2
NAD+
FAD+
2 H+ + 1/2 O2
H2O
ADP +
Electron transport chain
Electron transport and pumping of protons (H+),
which create an H+ gradient across the membrane
Chemiosmosis
ATP synthesis powered by the flow
Of H+ back across the membrane
synthase Q
Oxidative phosphorylation
Intermembrane
space
mitochondrial
matrix

34. CHEMIOSMOTIC PHOSPHORYLATION OXIDATIVE PHOSPHORYLATION
as H+ pass through, the rotor turns the rod and the movement of the rod causes conformational changes in the knob which then phosphorulates ADP into ATP
CHEMIOSMOTIC PHOSPHORYLATION or
OXIDATIVE PHOSPHORYLATION

35. INTERMEMBRANE SPACE H+
P i +
ADP
ATP
A rotor within the membrane spins clockwise when H+ flows past it down the H+ gradient.
A stator anchored in the membrane holds the knob stationary.
A rod (for “stalk”) extending into the knob also spins, activating catalytic sites in the knob.
Three catalytic sites in the stationary knob join inorganic
Phosphate to ADP to make ATP.
MITOCHONDRIAL MATRIX

36. END OF ELECTRON TRANSPORT CHAIN
Final electron acceptor is O2
for every 2 NADH or 1 FADH2 one O2 is reduced and forms water
Electron Transport Chain Animation

37. CELLULAR RESPIRATION: AN OVERVIEW
Overall Energy Yield = 36 – 38 ATP
Glycolysis: 2 ATP, 2 NADH
Kreb’s Cycle: 2 ATP, 8 NADH, 2 FADH2
ETC: ATP based on #’s of NADH and FADH2
# of NADH = 8 (Krebs) = 24 ATP
# of FADH2 = 2 = 4 ATP
Total ATP = 2 (Glyc) + 2 (Kreb’s) + 28 ATP = 32 ATP
Remaining 4 – 6 from the 2 NADH from Glycolysis

38. Glycolysis NADH transfers Hydrogen across membrane of mitochondria
membrane not permeable to NAD+
Transfers H’s to either NADH or FADH2
if to NADH = 3 ATP
if to FADH2 = 2 ATP

39. TOTAL Yield: about 38 ATP per glucose
ATP TOTALS:
Glycolysis: 2
Kreb’s:
ETC:
TOTAL Yield: about 38 ATP per glucose
efficiency of 40%
compared to a car which is at best 25%
Remaining energy lost as heat

40. Glycolysis Citric acid cycle
Electron shuttles
span membrane
CYTOSOL
2 NADH
2 FADH2
6 NADH
Glycolysis
Glucose 2
Pyruvate
Acetyl
CoA
Citric
acid
cycle
Oxidative
phosphorylation:
electron transport
and
chemiosmosis
MITOCHONDRION
by substrate-level
phosphorylation
by oxidative phosphorylation, depending
on which shuttle transports electrons
from NADH in cytosol
Maximum per glucose:
About
36 or 38 ATP
+ 2 ATP
+ about 32 or 34 ATP or

41. RELATED METABOLIC PROPERTIES
Glycolysis uses NAD+ to Oxidize Glucose
for glucose to continue to be used for the generation of energy the cell must recycle the NADH to NAD+
NEED A FINAL ELECTRON ACCEPTOR - usually Oxygen
WHAT HAPPENS WHEN THERE IS NO OXYGEN?
NADH has no place to put its hydrogens - glucose can’t be broken down
NEED ANOTHER ELECTRON ACCEPTOR:
with oxygen  aerobic
without Oxygen  anaerobic

42. Anaerobic Metabolic Pathways = Fermentation
Alcohol Fermentation: Irreversible
2 steps:
pyruvate is converted to acetylaldehyde by the removal of a carbon - forms CO2 - the bubbles in alcoholic beverages
acetalyaldehyde is reduced by NADH - forms ethanol and frees up NAD+ for glycolysis
Generates NO ENERGY
WHERE: bacteria and fungus cells

43. Pyruvate is reduced to lactate - frees up NAD+ for glycolysis
Lactic Acid Fermentation: Reversible
Pyruvate is reduced to lactate - frees up NAD+ for glycolysis
PRODUCES NO ENERGY and NO CO2
- burning and pain in cells
Lactate can be converted back to pyruvate when removed from cells and processed in liver

44. (a) Alcohol fermentation (b) Lactic acid fermentation
2 ADP + 2 P1
2 ATP
Glycolysis
Glucose
2 NAD+
2 NADH
2 Pyruvate
2 Acetaldehyde
2 Ethanol
(a) Alcohol fermentation
2 Lactate
(b) Lactic acid fermentation H OH
CH3 C
O – O O–
CO2 2

45. COMPARISON OF AEROBIC AND ANAEROBIC
ATP Generated per glucose
Aerobic: about 38
Anaerobic: 2
FINAL ELECTRON ACCEPTOR
CR - oxygen
Ferm - organic molecule

46. METABOLISM OF OTHER BIOLOGICAL MOLECULES
GLUCOSE:
break down of starch or glycogen
feeds directly into the process
Other Monosaccharides and Dissacharides - easily incorporated early in glycolysis

47. METABOLISM OF OTHER BIOLOGICAL MOLECULES
Proteins:
broken down into amino acids
most used to build proteins in cells - extra are processed by deaminification - removal of amine group
nitrogen group  urine
remaining portions enter into respiration dependent on structure

48. METABOLISM OF OTHER BIOLOGICAL MOLECULES
FATS:
glycerol and fatty acids
glycerol  glyceraldehyde phosphate
fatty acids: broken down into 2 carbon molecules  acetyl CoA
provide tremendous amounts of energy because of numerous carbon bonds
FATS GIVE TWICE AS MUCH ENERGY

49. METABOLISM OF OTHER BIOLOGICAL MOLECULES
HOWEVER: NOT ALL BIOMOLECULES OR INTERMEDIATES OF CELLULAR RESPIRATION ARE USED FOR PRODUCTION OF ENERGY
some are used to build other molecules

50. Glucose NH3 Pyruvate Amino acids Sugars Glycerol Fatty Glycolysis
Glyceraldehyde-3- P
Pyruvate
Acetyl CoA
NH3
Citric
acid
cycle
Oxidative
phosphorylation
Fats
Proteins
Carbohydrates

51. CONTROL OF METABOLISM Feedback inhibition:
too much ATP inhibits phosphofructokinase (first irreversible step in process)
stops generation of Pyruvate and thus the production of ATP
When ATP stores are low, AMP is formed and binds to phosphofructokinase to stimulate production of energy
Phosphofructokinase also sensitive to citrate - too much citrate - moves out of mitochondria and inhibits enzyme - slows glycolysis until citrate is consumed -
PREVENTS THE CELL FROM WASTING RESOURCES

52. Fructose-1,6-bisphosphate
Glucose
Glycolysis
Fructose-6-phosphate
Phosphofructokinase
Fructose-1,6-bisphosphate
Inhibits
Pyruvate
ATP
Acetyl CoA
Citric
acid
cycle
Citrate
Oxidative
phosphorylation
Stimulates
AMP + –