Aerobic vs.

Anaerobic Metabolism
• Heterotrophs divided into groups based on the efficiency of energy
production during cellular respiration.
– Aerobes: Use molecular oxygen as the final electron acceptor.
• Almost 20 times more energy is released compared to
anaerobes
• Advantage is the need for smaller quantity of food to
maintain given rate of metabolism
– Anaerobes: Use other molecules (e.g., pyruvic acid) as final
electron acceptor.
• Play important roles in specialized habitats
• Occurs when oxygen is absent or present in low quantities
• Energy yield is much lower than aerobic respiration
• Final electron acceptor still contains most of the energy
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stored
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Cellular Respiration
• Overview of Respiration
– Cellular respiration is aerobic metabolism.
• Oxidation of fuel molecules (removal of
electrons) to produce energy with
molecular oxygen acting as the final
electron acceptor.
• Hans Krebs, the British biochemist,
described three stages of cellular
respiration.
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 Three Stages of Respiration
• Three Stages of the Oxidation of Fuel Molecules
– Stage I
• Digestion of food molecules to small units
• No useful energy yield
– Stage II (Glycolysis)
• Small molecule converted into acetyl-CoA
• Small ATP yield (2 ATPs)
– Stage III (Krebs cycle and electron transport chain)
• Final common pathway for oxidation of fuel
molecules
37 • Large ATP yield (36–38 ATPs)
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Overview of Cellular Respiration

38 Figure 4.11 Overview of cellular respiration.

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 Glycolysis
• Glycolysis is a nearly universal pathway in living organisms.
– Occurs in cytoplasm
– Involves 10 enzymatically catalyzed reactions
• Glucose (and other 6-carbon monosaccharides) is split
into two molecules of pyruvic acid (three carbons
each)
• Net of two ATP molecules formed
– Uses two ATPs but releases four ATPs

Glucose + 2 ADP + 2 Pi + NAD+ → 2 Pyruvic acid + 2 NADH + 2 ATP

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Steps of Glycolysis

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Figure 4.12 Glycolysis.
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 NAD+ and NADH
• Nicotinamide adenine dinucleotide (NAD+) is a
derivative of the vitamin niacin.
– NAD+ accepts a hydrogen ion and electrons
removed from substrate molecules .
• NAD+ + 2H à NADH + H+
– Converted to reduced form, NADH
• Carrier molecule that conveys high-energy
electrons to the final electron transport
chain for ATP production
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Mobilization of Acetyl-CoA
• Acetyl-CoA is a critical intermediate compound in respiration.
– Two pyruvic acid molecules formed by glycolysis enter the
mitochondrion
• Each is oxidized, releasing a carbon as CO2.
• Each remaining two carbon residue condenses with coenzyme A (CoA) to
form acetyl coenzyme A and NADH.
– Will be oxidized in Krebs cycle, providing energized electrons to
generate ATP
– Also as crucial intermediate in lipid metabolism.

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 Formation of Acetyl-CoA

Figure 4.13 Formation of acetyl-CoA from pyruvic acid.

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Krebs Cycle
• Oxidation of acetyl-CoA takes place in the matrix of the
mitochondria during Krebs cycle.
– Acetyl-CoA condenses with 4-carbon acid (oxaloacetic acid)
– Through a cyclic series of reactions
• CoA is released
• Remaining two carbons from the acetyl group are released as CO2
• Oxaloacetic acid is regenerated

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 Products of the Krebs Cycle
• The overall products of the Krebs cycle are:
– Six additional NADH formed
– Two FADH2 formed
• Flavin adenine dinucleotide (FAD)
–Electron acceptor
–Reduced form as FADH2
– Two ATP molecules formed by substrate
level phosphorylation

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Steps of the Krebs Cycle

46 Figure 4.14 The Krebs cycle.

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 Electron Transport Chain
• Electron transport chain moves electrons and hydrogen ions to
final electron acceptor.
– Embedded in the inner mitochondrial membrane
– Transfer from NADH and FADH2 to molecular oxygen
– Carrier molecules in chain are large transmembrane protein-based
complexes
• Accept and release electrons in downhill fashion
• Energy is released with each transfer

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Hydrogen Ion Transport

• Energy is used to transport H+ into the inner membrane space
– Creates an H+ gradient
• H+ gradient drives the synthesis of ATP by chemiosmotic
coupling
– NADH and FADH2 donate electrons, which are shuttled down the
electron transport chain
– Movement of electrons activates a proton pump

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 ATP Synthesis
• H+ ions are pumped into the space between the inner and
outer mitochondrial membranes creating an H+ gradient.
• H+ ions diffuse back into the matrix through special ATP-
forming protein complexes called ATP synthase.
– Flow of H+ ions powers ATP synthesis.
– Oxygen then binds with these leftover H+ ions to form water.

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Products of the Electron Transport Chain

• Oxidation of one NADH yields three ATP
molecules.
• Oxidation of one FADH yields two ATP
molecules.
• This method of energy capture is called
oxidative phosphorylation.
– Formation of high-energy phosphate is
coupled to oxygen consumption.
– Most of the ATPs in living organisms are
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produced in the electron transport chain.
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 Oxidative Phosphorylation

Figure 4.15 Oxidative phosphorylation with formation of

51 water and ATP.
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Efficiency of Oxidative Phosphorylation

• The complete oxidation of glucose yields about
36 ATPs.
Glucose + 2 ATP + 36 ADP + 36 P + 6 O2 → 6
CO2 + 2 ADP + 36 ATP + 6 H2O

■ Overall efficiency of aerobic oxidation

of glucose: 38%
■ Efficiency of human-designed
machines: 5% to 10%
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 ATP Generated in Respiration
Copyright © McGraw-Hill Education. Permission required for reproduction or display.

TABLE 4.1
Calculation of Table ATP Molecules Generated in
Respiration
ATP Generated Source
4 Directly in glycolysis
2 As GTP (→ ATP) in Krebs cycle
4 From NADH in glycolysis
6 From NADH produced in pyruvic acid to acetyl-CoA
reaction
4 From reduced FAD in Krebs cycle
18 From NADH produced in Krebs cycle
38 Total
–2 Used in priming reactions in glycolysis
36 Net
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Pathway for oxidation of glucose and other carbohydrates

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 Anaerobic Glycolysis
• Generating ATP under anaerobic conditions
– In glycolysis, glucose is converted into
pyruvic acid.
– Oxidation of pyruvic acid cannot occur since
Krebs cycle and electron transport chain are
oxygen-requiring pathways.
– It is Only 1/18th as efficient as aerobic
metabolism.

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Fermentation Pathways
• Two general types of fermentation (anaerobic
glycolysis)
– Lactic acid fermentation (many animal cells)
• Reduces pyruvic acid to lactic acid
• Converts NADH into NAD+ and allows it to
pick up more H+ and electrons
– Alcoholic fermentation (yeast)
• Reduces pyruvic acid to ethanol with
release of CO2
56 • Also regenerates NAD+
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 Lactic Acid Fermentation

Figure 4.17 Anaerobic glycolysis: Lactic acid fermentation.

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Metabolism of Lipids
• Triglycerides are rich deposits of metabolic
energy.
– Hydrolyzed to glycerol and three fatty acid
chains
– Fatty acids are oxidized by sequential
removal of 2-carbon units as acetyl-CoA,
which then enter the Krebs cycle

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 Hydrolysis of Triglyceride

Figure 4.18 Hydrolysis of a triglyceride (neutral fat) by intracellular lipase.

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Products of Lipid Oxidation

• Oxidation of one molecule of 18-carbon stearic
acid yields 146 ATP molecules.
• Since there are 3 fatty acids in each triglyceride
molecule:
– A total of 440 ATP molecules are formed
(146 × 3).
• Breakdown of glycerol provides 22 additional
ATP molecules.
• Total energy: 462 ATPs.
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 Metabolism of Proteins
• Proteins are made of amino acids.
• Amino acids in excess of requirements for
protein synthesis and other biomolecules are
burned as fuel.
– Amino acids become fuel when nitrogen is
removed by deamination or transamination
• Deamination: Amino group splits to form
ammonia and keto acid.
• Transamination: Amino group transferred
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to a keto acid to form a new amino acid.
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Oxidation of Amino Acid

• Once nitrogen atoms are removed, the carbon
skeletons of amino acids can be completely
oxidized, usually by way of pyruvic acid or
acetic acid.
• The other product of amino acid degradation is
ammonia, which is highly toxic because it
inhibits respiration.
• Ammonia is then converted into nontoxic
forms as urea and uric acid.

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 Steps of Protein Oxidation

Figure 4.19 Fate of dietary protein.

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