Cellular Pathways that Harvest Chemical Energy

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Cellular Pathways that Harvest Chemical Energy
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Energy and Electrons from Glucose

• The sugar glucose (C6H12O6) is the most common
  form of energy molecule.
• Cells obtain energy from glucose by the chemical
  process of oxidation in a series of metabolic
  pathways.
• However, cells can also obtain energy from
  lipids, proteins and nucleic acids as well as
  carbohydrates.

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Energy and Electrons from Glucose

• Principles governing metabolic pathways
• Each reaction in the pathway is catalyzed by a
  specific enzyme.
• Metabolic pathways are similar in all organisms.
• In eukaryotes, many metabolic pathways are
  compartmentalized in organelles.
• The operation of each metabolic pathway can be
  regulated by the activities of key enzymes.

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Energy and Electrons from Glucose

• When burned in a flame, glucose releases heat,
  carbon dioxide, and water.
• C6H12O6 6 O2 6 CO2 6 H2O energy
• The same equation applies for the biological,
  metabolic use of glucose.

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Energy and Electrons from Glucose

• About half of the energy from glucose is
  collected in ATP.
• ?G for the complete conversion of glucose is
  686 kcal/mol.
• The reaction is therefore highly exergonic, and
  it drives the endergonic formation of ATP.

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Energy and Electrons from Glucose

• Three metabolic processes are used in the
  breakdown of glucose for energy
• Glycolysis
• Cellular respiration
• Fermentation

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Figure 7.1 Energy for Life
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Energy and Electrons from Glucose

• Glycolysis produces some usable energy and two
  molecules of a three-carbon sugar called
  pyruvate.
• Glycolysis begins glucose metabolism in all
  cells.
• Glycolysis does not require O2 it is an
  anaerobic metabolic process.

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Energy and Electrons from Glucose

• Cellular respiration uses O2 and occurs in
  aerobic (oxygen-containing) environments.
• Pyruvate is converted to CO2 and H2O.
• The energy stored in covalent bonds of pyruvate
  is used to make ATP molecules.

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Energy and Electrons from Glucose

• Fermentation does not involve O2. It is an
  anaerobic process.
• Pyruvate is converted into lactic acid or
  ethanol.
• Breakdown of glucose is incomplete less energy
  is released than by cellular respiration.

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Energy and Electrons from Glucose

• Redox reactions transfer the energy of electrons.
• A gain of one or more electrons or hydrogen atoms
  is called reduction.
• The loss of one or more electrons or hydrogen
  atoms is called oxidation.
• Whenever one material is reduced, another is
  oxidized.

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Figure 7.2 Oxidation and Reduction Are Coupled
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Energy and Electrons from Glucose

• An oxidizing agent accepts an electron or a
  hydrogen atom.
• A reducing agent donates an electron or a
  hydrogen atom.
• During the metabolism of glucose, glucose is the
  reducing agent (and is oxidized), while oxygen is
  the oxidizing agent (and is reduced).

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Energy and Electrons from Glucose

• The coenzyme NAD is an essential electron carrier
  in cellular redox reactions.
• NAD exists in an oxidized form, NAD, and a
  reduced form, NADH H.
• The reduction reaction requires an input of
  energy
• NAD 2H NADH H
• The oxidation reaction is exergonic
• NADH H ½ O2 NAD H2O

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Figure 7.3 NAD Is an Energy Carrier
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Figure 7.4 Oxidized and Reduced Forms of NAD
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Energy and Electrons from Glucose

• The energy-harvesting processes in cells use
  different combinations of metabolic pathways.
• With O2 present, four major pathways operate
• Glycolysis
• Pyruvate oxidation
• The citric acid cycle
• The respiratory chain (electron transport chain)
• When no O2 is available, glycolysis is followed
  by fermentation.

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Table 7.1 Cellular Locations for Energy Pathways
in Eukaryotes and Prokaryotes
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Glycolysis From Glucose to Pyruvate

• Glycolysis can be divided into two stages
• Energy-investing reactions that use ATP
• Energy-harvesting reactions that produce ATP

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Glycolysis From Glucose to Pyruvate

• The energy-harvesting reactions of glycolysis
• The first reaction (an oxidation) releases free
  energy that is used to make two molecules of NADH
  H, one for each of the two G3P molecules.
• Two other reactions each yield one ATP per G3P
  molecule. This part of the pathway is called
  substrate-level phosphorylation.
• The final product is two 3-carbon molecules of
  pyruvate.

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Figure 7.6 Glycolysis Converts Glucose to
Pyruvate (Part3)
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Figure 7.6 Glycolysis Converts Glucose to
Pyruvate (Part 4)
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Figure 7.7 Changes in Free Energy During
Glycolysis
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Pyruvate Oxidation

• Pyruvate is oxidized to acetate which is
  converted to acetyl CoA.
• Pyruvate oxidation is a multistep reaction
  catalyzed by an enzyme complex attached to the
  inner mitochondrial membrane.
• The acetyl group is added to coenzyme A to form
  acetyl CoA. One NADH H is generated during
  this reaction.

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Figure 7.8 Pyruvate Oxidation and the Citric
Acid Cycle (Part 1)
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The Citric Acid Cycle

• The citric acid cycle (Krebs Cycle) begins when
  the two carbons from the acetate are added to
  oxaloacetate, a 4-C molecule, to generate
  citrate, a 6-C molecule.
• A series of reactions oxidize two carbons from
  the citrate. With molecular rearrangements,
  oxaloacetate is formed, which can be used for the
  next cycle.
• For each turn of the cycle, three molecules of
  NADH H, one molecule of ATP, one molecule of
  FADH2, and two molecules of CO2 are generated.

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Figure 7.8 Pyruvate Oxidation and the Citric
Acid Cycle (Part 2)
For each molecule of glucose, the net gain is 6
NADH, 2 FADH2 and 2 ATP
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The Respiratory ChainElectrons, Protons, and
ATP Production

• The respiratory chain uses the reducing agents
  generated by pyruvate oxidation and the citric
  acid cycle. (NADH and FADH)
• The flow of electrons in a series of redox
  reactions causes the active transport of protons
  across the inner mitochondrial membrane, creating
  a proton concentration gradient.
• The protons then diffuse through proton channels
  down the concentration and electrical gradient
  back into the matrix of the mitochondria,
  creating ATP in the process.
• ATP synthesis by electron transport is called
  oxidative phosphorylation.

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The Respiratory ChainElectrons, Protons, and
ATP Production

• The respiratory chain consists of four large
  protein complexes bound to the inner
  mitochondrial membrane, plus cytochrome c and
  ubiquinone (Q).

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Figure 7.10 The Oxidation of NADH H
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The Respiratory ChainElectrons, Protons, and
ATP Production

• As electrons pass through the respiratory chain,
  protons are pumped by active transport into the
  intermembrane space against their concentration
  gradient.
• This transport results in a difference in
  electric charge across the membrane.
• The potential energy generated is called the
  proton-motive force.

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The Respiratory ChainElectrons, Protons, and
ATP Production

• Chemiosmosis is the coupling of the proton-motive
  force and ATP synthesis.
• NADH H or FADH2 yield energy upon oxidation.
• The energy is used to pump protons into the
  intermembrane space, contributing to the
  proton-motive force.
• The potential energy from the proton-motive force
  is harnessed by ATP synthase to synthesize ATP
  from ADP.

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Figure 7.12 A Chemiosmotic Mechanism Produces
ATP (Part 1)
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Figure 7.12 A Chemiosmotic Mechanism Produces
ATP (Part 2)
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The Respiratory ChainElectrons, Protons, and
ATP Production

• Synthesis of ATP from ADP is reversible.
• The synthesized ATP is transported out of the
  mitochondrial matrix as quickly as it is made.
• The proton gradient is maintained by the pumping
  of the electron transport chain.

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The Respiratory ChainElectrons, Protons, and
ATP Production

• Two key experiments demonstrated that
• A proton gradient across a membrane can drive ATP
  synthesis.
• The enzyme ATP synthase is the catalyst for this
  reaction.

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Figure 7.13 Two Experiments Demonstrate the
Chemiosmotic Mechanism
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Fermentation ATP from Glucose, without O2

• When there is an insufficient supply of O2, a
  cell cannot reoxidize cytochrome c.
• Then QH2 cannot be oxidized back to Q, and soon
  all the Q is reduced.
• This continues until the entire respiratory chain
  is reduced.
• NAD and FAD are not generated from their reduced
  form.
• Pyruvate oxidation stops, due to a lack of NAD.
• Likewise, the citric acid cycle stops, and if the
  cell has no other way to obtain energy, it dies.

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Fermentation ATP from Glucose, without O2

• Some cells under anaerobic conditions continue
  glycolysis and produce a limited amount of ATP if
  fermentation regenerates the NAD to keep
  glycolysis going.
• Fermentation uses NADH H to reduce pyruvate,
  and consequently NAD is regenerated.

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Fermentation ATP from Glucose, without O2

• Some organisms are confined to anaerobic
  environments and use only fermentation.
• These organisms lack the molecular machinery for
  oxidative phosphorylation.
• They also lack enzymes to detoxify the toxic
  by-products of O2, such as H2O2.

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Fermentation ATP from Glucose, without O2

• In lactic acid fermentation, an enzyme, lactate
  dehydrogenase, uses the reducing power of NADH
  H to convert pyruvate into lactate.
• NAD is replenished in the process.
• Lactic acid fermentation occurs in some
  microorganisms and in muscle cells when they are
  starved for oxygen.

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Figure 7.14 Lactic Acid Fermentation
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Fermentation ATP from Glucose, without O2

• Alcoholic fermentation involves the use of two
  enzymes to metabolize pyruvate.
• First CO2 is removed from pyruvate, producing
  acetaldehyde.
• Then acetaldehyde is reduced by NADH H,
  producing NAD and ethanol.

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Figure 7.15 Alcoholic Fermentation
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Contrasting Energy Yields

• A total of 36 ATP molecules can be generated from
  each glucose molecule in glycolysis and cellular
  respiration.
• Each NADH H generates 3 ATP molecules, and
  each FADH2 generates 2 ATP by the chemiosmotic
  mechanism.
• Fermentation has a net yield of 2 ATP molecules
  from each glucose molecule.
• The end products of fermentation contain much
  more unused energy than the end products of
  aerobic respiration.

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Figure 7.16 Cellular Respiration Yields More
Energy Than Glycolysis Does (Part 1)
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Figure 7.16 Cellular Respiration Yields More
Energy Than Glycolysis Does (Part 2)
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Relationships between Metabolic Pathways

• Glucose utilization pathways can yield more than
  just energy. They are interchanges for diverse
  biochemical traffic.
• Intermediate chemicals are generated that are
  substrates for the synthesis of lipids, amino
  acids, nucleic acids, and other biological
  molecules.

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Figure 7.17 Relationships Among the Major
Metabolic Pathways of the Cell
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Relationships between Metabolic Pathways

• What happens if inadequate food molecules are
  available?
• Glycogen stores in muscle and liver are used
  first.
• Fats are used next. But the brain can only use
  glucose, so it must be synthesized by
  gluconeogenesis which uses mostly amino acids.
• Therefore, proteins must be broken down.
• After fats are depleted, proteins alone provide
  energy.

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Relationships between Metabolic Pathways

• The levels of the products and substrates of
  energy metabolism are remarkably constant.
• Cells regulate the enzymes of catabolism and
  anabolism to maintain a balance, or metabolic
  homeostasis.

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Regulating Energy Pathways

• Metabolic pathways work together to provide cell
  homeostasis.
• Positive and negative feedback control whether a
  molecule of glucose is used in anabolic or
  catabolic pathways.

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Regulating Energy Pathways

• The amount and balance of products a cell has is
  regulated by allosteric control of enzyme
  activities.
• Control points use both positive and negative
  feedback mechanisms.
• The main control point in glycolysis is the
  enzyme phosphofructokinase.
• This enzyme is inhibited by ATP and activated by
  ADP and AMP.

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Regulating Energy Pathways

• The main control point of the citric acid cycle
  is the enzyme isocitrate dehydrogenase which
  converts isocitrate to a-ketoglutarate.
• NADH H and ATP are inhibitors of this enzyme.
  NAD and ADP are activators of it.
• Accumulation of isocitrate and citrate occurs,
  but is limited by the inhibitory effects of high
  ATP and NADH.
• Citrate acts as an additional inhibitor to slow
  the fructose 6-phosphate reaction of glycolysis
  and also switches acetyl CoA to the synthesis of
  fatty acids.

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Figure 7.20 Feedback Regulation of Glycolysis
and the Citric Acid Cycle (Part 1)
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Figure 7.20 Feedback Regulation of Glycolysis
and the Citric Acid Cycle (Part 2)