Cellular Respiration:
Harvesting Chemical Energy
PowerPoint® Lecture Presentations for
         Biology
       Eighth Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Overview: Life Is Work
• Living cells require energy from outside
  sources
• Some animals, such as the giant panda, obtain
  energy by eating plants, and some animals
  feed on other organisms that eat plants
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-1
• Energy flows into an ecosystem as sunlight
  and leaves as heat
• Photosynthesis generates O2 and organic
  molecules, which are used in cellular
  respiration
• Cells use chemical energy stored in organic
  molecules to regenerate ATP, which powers
  work
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-2
                       Light
                       energy
           ECOSYSTEM
                             Photosynthesis
                             in chloroplasts
             CO2 + H2O                             Organic
                                                           +O
                                                  molecules 2
                           Cellular respiration
                            in mitochondria
                                  ATP
                   ATP powers most cellular work
                         Heat
                         energy
Catabolic Pathways and Production of ATP
• The breakdown of organic molecules is
  exergonic
• Fermentation is a partial degradation of
  sugars that occurs without O2
• Aerobic respiration consumes organic
  molecules and O2 and yields ATP
• Anaerobic respiration is similar to aerobic
  respiration but consumes compounds other
  than O2
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• Cellular respiration includes both aerobic and
  anaerobic respiration but is often used to refer
  to aerobic respiration
• Although carbohydrates, fats, and proteins are
  all consumed as fuel, it is helpful to trace
  cellular respiration with the sugar glucose:
         C6H12O6 + 6 O2 → 6 CO2 + 6 H2O + Energy
                                       (ATP + heat)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Oxidation of Organic Fuel Molecules During
Cellular Respiration
• During cellular respiration, the fuel (such as
  glucose) is oxidized, and O2 is reduced:
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-UN3
             becomes oxidized
                          becomes reduced
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)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-6-1
               Electrons
                carried
               via NADH
               Glycolysis
    Glucose             Pyruvate
      Cytosol
                  ATP
             Substrate-level
             phosphorylation
Fig. 9-6-2
               Electrons                               Electrons carried
                carried                                 via NADH and
               via NADH                                     FADH2
               Glycolysis                          Citric
                                                   acid
    Glucose             Pyruvate                   cycle
                                   Mitochondrion
      Cytosol
                  ATP                          ATP
             Substrate-level               Substrate-level
             phosphorylation              phosphorylation
Fig. 9-6-3
               Electrons                               Electrons carried
                carried                                 via NADH and
               via NADH                                     FADH2
                                                                       Oxidative
               Glycolysis                          Citric          phosphorylation:
                                                   acid            electron transport
    Glucose             Pyruvate                   cycle                  and
                                                                     chemiosmosis
                                   Mitochondrion
      Cytosol
                  ATP                          ATP                           ATP
             Substrate-level               Substrate-level                Oxidative
             phosphorylation              phosphorylation              phosphorylation
• The process that generates most of the ATP is
  called oxidative phosphorylation because it
  is powered by redox reactions
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• Oxidative phosphorylation accounts for almost
  90% of the ATP generated by cellular
  respiration
• A smaller amount of ATP is formed in glycolysis
  and the citric acid cycle by substrate-level
  phosphorylation
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-7
           Enzyme            Enzyme
                  ADP
             P
      Substrate                   +   ATP
                        Product
Glycolysis harvests chemical energy by oxidizing
glucose to pyruvate
• Glycolysis (“splitting of sugar”) breaks down
  glucose into two molecules of pyruvate
• Glycolysis occurs in the cytoplasm and has two
  major phases:
        – Energy investment phase
        – Energy payoff phase
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-8
             Energy investment phase
                               Glucose
                        2 ADP + 2 P            2 ATP   used
              Energy payoff phase
                        4 ADP + 4 P            4 ATP   formed
               2 NAD+ + 4 e– + 4 H+           2 NADH + 2 H+
                                             2 Pyruvate + 2 H2O
             Net
                               Glucose    2 Pyruvate + 2 H2O
           4 ATP formed – 2 ATP used      2 ATP
                   2 NAD+ + 4 e– + 4 H+   2 NADH + 2 H+
                     Glucose
            ATP
                           1
                          Hexokinase
              ADP
              Glucose-6-phosphate
                           2
                          Phosphoglucoisomerase
                                                                          Fructose-
                                                                     1, 6-bisphosphate
                                                                                  4
              Fructose-6-phosphate
                                                                                  Aldolase
            ATP
                           3
                          Phosphofructokinase
              ADP
                                                                              5
                                                                          Isomerase
                   Fructose-
              1, 6-bisphosphate
                           4
                          Aldolase
                        5
                    Isomerase
                                                       Dihydroxyacetone                  Glyceraldehyde-
                                                          phosphate                       3-phosphate
Dihydroxyacetone                     Glyceraldehyde-
   phosphate                           3-phosphate
Fig. 9-9-9
               2 NAD+            6
                                Triose phosphate
                                dehydrogenase
                                    2 Pi
             2 NADH
               + 2 H+
             2 1, 3-Bisphosphoglycerate
                  2 ADP
                                 7 Phosphoglycerokinase
              2 ATP
                                                          2    Phosphoenolpyruvate
                                                              2 ADP
              2     3-Phosphoglycerate
                                 8
                                Phosphoglyceromutase                        10
                                                                            Pyruvate
                                                          2 ATP             kinase
              2     2-Phosphoglycerate
                                 9
                                Enolase
                  2 H2O
              2 Phosphoenolpyruvate
               2 ADP
                                10
                                Pyruvate kinase
              2 ATP
                                                          2           Pyruvate
              2           Pyruvate
The citric acid cycle completes the energy-yielding
oxidation of organic molecules
• In the presence of O2, pyruvate enters the
  mitochondrion
• Before the citric acid cycle can begin, pyruvate
  must be converted to acetyl CoA, which links
  the cycle to glycolysis
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-10
            CYTOSOL                    MITOCHONDRION
                           NAD+       NADH + H+
                       1                   3
                                                  Acetyl CoA
   Pyruvate                CO2    Coenzyme A
   Transport protein
• 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Pyruvate
                                 CO2
             NAD+
                                  CoA
           NADH
           + H+     Acetyl CoA
                           CoA
                                  CoA
                         Citric
                         acid
                         cycle           2 CO2
   FADH2                                  3 NAD+
       FAD                              3 NADH
                                         + 3 H+
                            ADP + P i
                      ATP
• 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-12-1
                  Acetyl CoA
                             CoA—SH
              Oxaloacetate
                                Citrate
                      Citric
                      acid
                      cycle
Fig. 9-12-2
                  Acetyl CoA
                             CoA—SH
                         1                    H2O
              Oxaloacetate
                                          2
                                Citrate
                                                Isocitrate
                      Citric
                      acid
                      cycle
Fig. 9-12-3
                  Acetyl CoA
                             CoA—SH
                         1                    H2O
              Oxaloacetate
                                          2
                                Citrate
                                                Isocitrate
                                                       NAD+
                      Citric                             NADH
                                                3
                      acid                                + H+
                      cycle
                                                       CO2
                                                     -Keto-
                                                     glutarate
Fig. 9-12-4
                  Acetyl CoA
                              CoA—SH
                          1                         H2O
              Oxaloacetate
                                           2
                                 Citrate
                                                      Isocitrate
                                                                 NAD+
                       Citric                         3
                                                                  NADH
                       acid                                        + H+
                       cycle
                                                                 CO2
                                       CoA—SH
                                                            -Keto-
                                                            glutarate
                                               4
                                                           CO2
                                            NAD+
                                                   NADH
                                Succinyl            + H+
                                  CoA
Fig. 9-12-5
                     Acetyl CoA
                                   CoA—SH
                               1                            H2O
                Oxaloacetate
                                                   2
                                         Citrate
                                                              Isocitrate
                                                                         NAD+
                           Citric                                         NADH
                                                              3
                           acid                                            + H+
                           cycle
                                                                         CO2
                                              CoA—SH
                                                                    -Keto-
                                                                    glutarate
                                                       4
                          CoA—SH
                           5
                                                                   CO2
                                                   NAD+
              Succinate            Pi                      NADH
                     GTP GDP            Succinyl            + H+
                                          CoA
                   ADP
                     ATP
Fig. 9-12-6
                                    Acetyl CoA
                                                  CoA—SH
                                              1                            H2O
                                Oxaloacetate
                                                                  2
                                                        Citrate
                                                                             Isocitrate
                                                                                        NAD+
                                           Citric                                        NADH
                                                                             3
                                           acid                                           + H+
                                           cycle
                                                                                        CO2
                        Fumarate                             CoA—SH
                                                                                   -Keto-
                                                                                   glutarate
                            6                                         4
                                        CoA—SH
              FADH2                      5
                                                                                  CO2
                                                                  NAD+
                      FAD
                            Succinate             Pi                      NADH
                                    GTP GDP            Succinyl            + H+
                                                         CoA
                                  ADP
                                     ATP
Fig. 9-12-7
                                          Acetyl CoA
                                                       CoA—SH
                                                   1                            H2O
                                      Oxaloacetate
                                                                       2
                            Malate                           Citrate
                                                                                  Isocitrate
                                                                                             NAD+
                                                 Citric                           3
                                                                                              NADH
                        7
                                                 acid                                          + H+
              H2O                                cycle
                                                                                             CO2
                              Fumarate                            CoA—SH
                                                                                        -Keto-
                                                                                        glutarate
                                  6                                        4
                                              CoA—SH
                    FADH2                      5
                                                                                       CO2
                                                                       NAD+
                            FAD
                                  Succinate            Pi                      NADH
                                          GTP GDP           Succinyl            + H+
                                                              CoA
                                        ADP
                                           ATP
Fig. 9-12-8
                                           Acetyl CoA
                                                        CoA—SH
                        NADH
                         +H+                        1                            H2O
                     NAD+
                                   8   Oxaloacetate
                                                                        2
                            Malate                            Citrate
                                                                                   Isocitrate
                                                                                              NAD+
                                                  Citric                           3
                                                                                               NADH
                        7
                                                  acid                                          + H+
              H2O                                 cycle
                                                                                              CO2
                               Fumarate                            CoA—SH
                                                                                         -Keto-
                                                                                         glutarate
                                  6                                         4
                                               CoA—SH
                    FADH2                       5
                                                                                        CO2
                                                                        NAD+
                            FAD
                                  Succinate             Pi                      NADH
                                           GTP GDP           Succinyl            + H+
                                                               CoA
                                         ADP
                                            ATP
During oxidative phosphorylation, chemiosmosis
couples electron transport to ATP synthesis
• Following glycolysis and the citric acid cycle,
  NADH and FADH2 account for most of the
  energy extracted from food
• These two electron carriers donate electrons to
  the electron transport chain, which powers ATP
  synthesis via oxidative phosphorylation
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-13
                   NADH
            50
                 2 e–
                        NAD+
                                          FADH2
                                        2 e–     FAD
                                                          Multiprotein
            40                           FAD             complexes
                 FMN
                         Fe•S          Fe•S 
                                   Q
                                                        
                                         Cyt b
                                                 Fe•S
            30
                                                        Cyt c1                      I
                                                                 Cyt c              V
                                                                         Cyt a
                                                                                 Cyt a3
            20
            10                                                                   2 e–
                                                                     (from NADH
                                                                        or FADH2)
             0                                                      2 H+ + 1/2 O2
                                                                                        H2O
• Electrons are transferred from NADH or FADH2
  to the electron transport chain
• Electrons are passed through a number of
  proteins including cytochromes (each with an
  iron atom) 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-14
            INTERMEMBRANE SPACE
                            H+
                                  Stator
                    Rotor
            Internal
            rod
            Cata-
            lytic
            knob
             ADP
              +
              P                  ATP
                i
            MITOCHONDRIAL MATRIX
• The energy stored in a H+ gradient across a
  membrane couples the redox reactions of the
  electron transport chain to ATP synthesis
• The H+ gradient is referred to as a proton-
  motive force, emphasizing its capacity to do
  work
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-16
                                                                        H+
                                               H+
                         H+
                                                                                                  H+
   Protein complex                                      Cyt c
   of electron
   carriers
                                                                   V
                                     Q
                                           
                                                                                                            ATP
                                                                                                            synthase
                                
                                                         2 H+ + 1/2O2           H2O
                                FADH2
                                         FAD
            NADH              NAD+
                                                                                      ADP + P i        ATP
      (carrying electrons
      from food)
                                                                                                  H+
                                     1 Electron transport chain                            2 Chemiosmosis
                                                    Oxidative phosphorylation
An Accounting of ATP Production by Cellular
Respiration
• During cellular respiration, most energy flows in
  this sequence:
      glucose → NADH → electron transport chain
      → proton-motive force → ATP
• About 40% of the energy in a glucose molecule
  is transferred to ATP during cellular respiration,
  making about 38 ATP
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-17
  CYTOSOL       Electron shuttles                                                 MITOCHONDRION
                span membrane               2 NADH
                                               or
                                            2 FADH2
             2 NADH                         2 NADH                   6 NADH   2 FADH2
            Glycolysis                                                                  Oxidative
                       2                        2          Citric                   phosphorylation:
      Glucose       Pyruvate                  Acetyl       acid                     electron transport
                                               CoA         cycle                           and
                                                                                      chemiosmosis
             + 2 ATP                                       + 2 ATP                       + 34 ATP
                                    Maximum per glucose:   38 ATP
Fermentation and anaerobic
respiration enable cells to produce ATP without
the use of oxygen
• 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• Anaerobic respiration uses an electron
  transport chain with an electron acceptor other
  than O2, for example sulfate
• Fermentation uses phosphorylation instead of
  an electron transport chain to generate ATP
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-18a
                         2 ADP + 2 P i         2 ATP
              Glucose             Glycolysis
                                                           2 Pyruvate
                            2 NAD+          2 NADH                2 CO2
                                          + 2 H+
             2 Ethanol                                 2 Acetaldehyde
        (a) Alcohol fermentation
• 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-18b
                            2 ADP + 2 P i         2 ATP
                 Glucose             Glycolysis
                              2 NAD+           2 NADH
                                             + 2 H+
                                                          2 Pyruvate
                2 Lactate
             (b) Lactic acid fermentation
Fermentation and Aerobic Respiration Compared
• Both processes use glycolysis to oxidize
  glucose and other organic fuels to pyruvate
• The processes have different final electron
  acceptors: an organic molecule (such as
  pyruvate or acetaldehyde) in fermentation and
  O2 in cellular respiration
• Cellular respiration produces 38 ATP per
  glucose molecule; fermentation produces 2
  ATP per glucose molecule
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-19
                             Glucose
                                  Glycolysis
            CYTOSOL
                             Pyruvate
            No O2 present:          O2 present:
            Fermentation             Aerobic cellular
                                      respiration
                                                     MITOCHONDRION
             Ethanol                    Acetyl CoA
                or
             lactate
                                                     Citric
                                                     acid
                                                     cycle