Ch. 9 Cellular Respiration


An Overview


There are three stages that occur in cellular respiration:

1.      Glycolysis

·        Occurs in the cytoplasm

·        is the partial oxidation of glucose (6 carbons) into 2 molecules of pyruvate (pyruvic acid) which has 3 carbons

2.      Krebs cycle (aka citric acid cycle)

·        Occurs in the mitochondrial matrix

·        Completes the oxidation of glucose

                                                                           i.      Breaks down pyruvate into CO2

3.      Electron transport chain and oxidative phosphorylation

·        Occurs at the inner membranes of the mitochondria

·        Accepts energized electrons from reduced coenzyme carrier molecules (NADH and FADH2).

·        Uses the movement of electrons to create ATP in oxidative phosphorylation.  Produces about 90% of ATP. 

o       The electrons were harvested during glycolysis and the Krebs cycle. 

o       Oxygen pulls the electrons through a series of reactions in the electron transport chain to successively lower energy states


Glycolysis: oxidizes glucose to form pyruvate


Catabolic pathway during which a 6 carbon glucose molecule is split into two 3 carbon sugars which are then oxidized and rearranged by a step-wise metabolic process that produces two molecules of pyruvic acid.

·        Each reaction in glycolysis is catalyzed by its own specific enzyme in the cytoplasm

·        No CO2 is released in the oxidation of glucose to pyruvate. 

·        Can occur either with or without O2


The reactions of glycolysis occur in 2 phases:

1.  Energy investment phase:  a 5-step process that splits glucose in two.  This process consumes ATP.

            Step 1:  glucose enters the cell and carbon # 6 is phosphorylated (phosphate bonds to it).  This reaction uses ATP.

            Step 2:  an enzyme called an isomerase catalyzes the reaction that changes the structure of glucose 6-phosphate to its isomer fructose 6- phosphate.

            Step 3:  Carbon # 1 of fructose 6-phosphate is phosphorylated.  Uses an ATP.

            Step 4:  Fructose 1,6 diphosphate is cut into two non-identical three-carbon sugars in an enzyme controlled reaction.  This is the reaction that gives glycolysis its name.

Step 5: Enzyme-controlled reaction that allows the two sugars to be converted to the other.  


2.  Energy yielding phase:  the 2 intermediate 3 carbon molecules are oxidized and ATP and NADH are produced.

  • Net gain of 2 ATP by substrate level phosphorylation (the production of ATP by the direct transfer of PO4 from an intermediate substrate to ADP.  Reaction is controlled by enzymes)

·        2 molecules of NAD are reduced to form NADH.  Energy in the high-energy electrons of NADH will be used to make ATP in oxidative phosphorylation (ATP production from the exergonic transfer of electron from food molecules to a final electron acceptor, in this case O2.


Step 1:  2 enzyme-catalyzed reactions, one reduces NAD to NADH and the other phosphorylates the 2 sugars.  2 NADH molecules are produced from every molecule of glucose.

Step 2:  ATP is produced in substrate level phosphorylation.  PO4 is transferred from the phosphorylated sugars to ADP.  Produces 2 ATP molecules from each glucose molecule.  This replaces the 2 ATP used in the energy investment phase.

Step 3:  Prepares for the next reaction.  Moves the phosphate from Carbon #3 to Carbon #2.

Step 4:  Enzymes remove water.  This makes the bond holding the phosphate to Carbon #2 weak and unstable.

Step 5:  2 ATP molecules are produced by substrate level phosphorylation.


Summary equation:


C6H12O6  + 2 NAD + 2 ATP --->  2 C3H4O3 + 2 H2O + 2 NADH + 2 H+ + 2 ATP


Glucose is oxidized into 2 molecules of pyruvic acid in an exergonic reaction.  Most of the energy is conserved in the high-energy electrons of NADH and in the phosphate bonds of ATP.



Krebs Cycle


The Krebs cycle completes the oxidation of organic molecules.  It releases the energy that is stored in the 2 molecules of pyruvate.  Pyruvate can only be completely oxidized in the presence of oxygen.


1.  Before we can enter the Krebs cycle, we must form acetyl Co-A

·        Pyruvic acid molecules are moved from the cytoplasm into the mitochondria by carrier proteins in the mitochondrial membrane.  Once inside the mitochondrion, pyruvate is converted to acetyl Co-A in a reaction that uses multiple enzymes.

o       CO2 is removed from pyruvate’s carboxyl group, changing it from a 3 carbon to a 2-carbon compound.  CO2 is released.

o       The 2-carbon molecule is oxidized to form acetate.  NAD is reduced to NADH in the process and 2 NADH molecules are produced.

o       Coenzyme A, a compound formed from vitamin A, attaches to the acetate and forms acetyl Co-A, which is much more reactive than pyruvate.


2.  Krebs cycle


For every turn of the Krebs cycle:

·        2 carbons enter in the acetyl part of acetyl Co-A.

·        2 different carbons are oxidized and leave as CO2

·        3 NADH and 1 FADH2 are produced

·        1 ATP molecule is produced by substrate level phosphorylation

·        Oxaloacetate must be regenerated


For every glucose molecule that is split during glycolysis:

·        2 acetyl fragments are produced

·        2 turns of the Krebs cycle must be completed to completely oxidize glucose


Steps of the Krebs cycle:  each step is enzyme mediated


1.      Acetyl Co-A breaks apart and the 2-carbon acetate bonds to a 4-carbon molecule of oxaloacetate (a compound found naturally in the mitochondrial matrix) and forms citric acid.

2.      Citric acid is converted to its isomer, isocitric acid.

3.      2 things happen:

a.       Isocitric acid loses CO2 leaving a 5 carbon molecule

b.      The 5 carbon compound is oxidized and NAD is reduced

4.      Catalyzed by multiple enzymes:

a.       CO2 is removed from the 5 carbon molecule

b.      Remaining 4 carbon molecule is oxidized and NAD is reduced

5.      Substrate level phosphorylation occurs.  1 ATP is made.

6.      A molecule is oxidized FAD is reduced to form FADH2

7.      Water is added to make the next reaction possible

8.       A molecule is oxidized and NAD is reduced to form NADH and oxaloacetate is regenerated so the cycle can begin again.


2 turns of the Krebs cycle produce the following form every glucose molecule:

      6 CO2 molecules 

      2 ATP molecules are created by substrate level phosphorylation

      6 NADH molecules

      2 FADH2 molecules


Electron Transport Chain


ETC is made of electron carrier molecules embedded in the inner mitochondrial membrane.  Each carrier is more electronegative than the one before it, so the electrons are pulled down the chain until they reach the final electron acceptor, oxygen.

·        Most of the carriers in ETC are proteins that are bound to cofactors.  It is the cofactors that accept and donate electrons.


Protein Electron Carriers




iron-sulfur proteins


cytochromes (protein that contains a heme group.  There are different cytochromes because the heme groups have different proteins)

flavin mononucleotide (FMN)


iron and sulfur


heme group (4 organic rings surrounding a single iron atom.  It is the iron that transfers electrons)


Sequence of reactions in the ETC:


NADH is oxidized and flavoprotein is reduced.  High-energy electrons are transferred from NADH to FMN



Flavoprotein is oxidized as it passes electrons to an iron-sulfur protein (FeS)



FeS is oxidized as it passes electrons to the only non-protein compound in the chain, uniquinone (Q)



Q passes electrons to a succession of cytochrome molecules



Cytochrome a3, the last carrier in the chain, passes electrons to molecular oxygen, O2



As O2 is reduced, it forms water.  For every 2 NADH molecules, one O2 is reduced, and 2 H2O molecules are made.



Note:  the ETC DOES NOT make ATP directly.  It generates a proton gradient on the inner membrane of the mitochondria.  This stores chemical potential energy that can be used to phosphorylate ADP.



Chemiosmosis:  the joining of the processes of exergonic electron flow down an electron transport chain to endergonic ATP production by creating a proton gradient across a membrane.  The proton gradient drives ATP synthesis as protons diffuse back across the membrane.

·        Empathasizes the link between phosphorylation and proton gradients

·        Makes oxidative phosphorylation (in cellular respiration) possible and photophosphorylation (in photosynthesis) possible

·        Can only make ATP with the help of the enzyme ATP synthase


Review of the Process


Energy flow sequence:


Glucose -> NADH -> ETC -> proton gradient -> ATP



ATP produced by substrate level phosphorylation

Reduced co-enzyme

ATP produced by oxidative phosphorylation




Oxidation of pyruvic acid


Krebs cycle

2 (net)













4 – 6







6 – 8






                                                                                                                        Total:  36-38





Enables cells to produce ATP without oxygen.


1.      Glycolysis occurs exactly as it does in aerobic respiration, but in anaerobic respiration, pyruvate is reduced and NAD is regenerated.  This prevents the cell from exhausting its supply of NAD that is necessary for aerobic respiration.

2.      The pyruvate then undergoes fermentation.  There are 2 types of fermentation.

a.       Alcoholic fermentation:  occurs in plants, yeast and bacteria.  Pyruvate is converted to ethanol.

1.      Pyruvate loses CO2 and is converted to the 2-carbon compound acetaldehyde.

2.      NADH is oxidized and acetaldehyde id reduced to ethanol


b.      Lactic acid fermentation:  occurs in animal cells.  Pyruvate is converted to lactic acid.  Used to make cheese and yogurt and in human muscle cells when oxygen is scarce.

1.      NADH is oxidized and pyruvate is converted to lactic acid



Aerobic respiration


Uses glycolysis to oxidize glucose to form pyruvate and produce 2 ATP


NADH reduces pyruvate

Electrons released are not used to make ATP


Electrons carried by NADH are used to power oxidative phosphorylation


Pyruvate is the final electron acceptor


Oxygen is the final electron acceptor


Amount of ATP produced


Requires oxygen