Metabolism: Fueling Cell Growth

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MetabolismFueling Cell Growth

• Chapter 6

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Preview

• Principles of metabolism
• Metabolism, catabolism, anabolism, energy, redox
  reaction.
• Central metabolic pathway
• Glycolysis, TCA
• Respiration
• Electron transport chain
• Fermentation

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Metabolism

• Chemical reactions to keep an organism alive.
• Basic needs

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Principles of Metabolism

• Metabolism is broken down into two components
• Anabolism
• Catabolism
• Catabolism
• Degradative reactions
• Reactions produce energy from the break down of
  larger molecules
• Anabolism
• Reactions involved in the synthesis of cell
  components
• Anabolic reactions require energy
• Anabolic reactions utilize the energy produced
  from catabolic reactions

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Metabolic Pathways
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Principles of Metabolism
Glycolysis
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Energy

• Definition
• Free energy-energy released by breaking chemical
  bonds
• reactants have more free energy
• Exergonic reaction
• products have more energy
• Endergonic reaction
• Energy source
• Compound broken down to release energy
• Common energy sources

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Energy

• Oxidizing energy source to release energy

Gas O2
CO2H2Oenergy
GlucoseO2
CO2 H2O energy
Oxidization gain of oxygen, loss of hydrogen,
loss of electron
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Harvesting Energy

• Oxidation/reduction reactions (redox reactions)

electron acceptor
electron donor
LEO - Lose electrons oxidized GER - Gain
electrons reduced

• Protons often follow electrons (i.e. a hydrogen
  atom is extracted/added e- H H )
• General rules
• If a compound gains oxygen or loses hydrogen, the
  reaction is an oxidation
• If a compound loses oxygen or gains hydrogen, the
  reaction is a reduction

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Harvesting Energy
The role of electron carriers
In redox reactions, protons often follow
electrons
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Harvesting Energy
The role of ATP
energy currency
Adenosine triphosphate
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Harvesting Energy
The role of ATP
energy currency
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Harvesting Energy
Synthesizing ATP

• Substrate-level phosphorylation

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Harvesting Energy
Synthesizing ATP

• Substrate-level phosphorylation

• Oxidative phosphorylation
• Photophosphorylation

• Other methods involve an electron transport chain
  and redox reaction

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Principles of Metabolism
Synthesizing ATP

• Substrate-level phosphorylation
• Oxidative phosphorylation - chemical energy is
  used to create the proton motive force (involves
  an electron transport chain) the energy of
  proton motive force is harvested by making ATP
• Photophosphorylation - radiant energy is used to
  create the proton motive force (involves an
  electron transport chain) the energy of proton
  motive force is harvested by making ATP

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Central metabolic pathway

• Central pathways are catabolic and provide
• Energy
• Reducing power
• Precursor metabolites
• Central metabolic pathways
• Glycolysis
• Pentose phosphate pathway
• Tricarboxcylic acid cycle

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Central Metabolic Pathways
Glycolysis (aka Embden-Meyerhoff pathway,
glycolytic pathway)
glucose? 2 pyruvate
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Central Metabolic Pathways
Glycolysis (aka Embden-Meyerhoff pathway,
glycolytic pathway)
glucose? 2 pyruvate

• 2 ATP (net gain)
• 2 spent 4 made
• 2 NADH
• 6 precursor metabolites

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Central Metabolic Pathways
Glycolysis (aka Embden-Meyerhoff pathway,
glycolytic pathway)
glucose? 2 pyruvate

• 2 ATP (net gain)
• 2 spent 4 made
• 2 NADH
• 6 precursor metabolites

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Central Metabolic Pathways
Glycolysis (aka Embden-Meyerhoff pathway,
glycolytic pathway)
glucose? 2 pyruvate

• 2 ATP (net gain)
• 2 spent 4 made

• 2 NADH

• 6 precursor metabolites

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Central Metabolic Pathways
Pentose phosphate pathway
glucose? intermediate of glycolysis

• NADPH (amount varies)
• 2 precursor metabolites

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Central Metabolic Pathways
Pentose phosphate pathway
glucose? intermediate of glycolysis

• NADPH (amount varies)
• 2 precursor metabolites

Primary role is biosynthesis ignored in
energy-yield calculations
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Central Metabolic Pathways
Pentose phosphate pathway
glucose? intermediate of glycolysis

• NADPH (amount varies)
• 2 precursor metabolites

Primary role is biosynthesis ignored in
energy-yield calculations
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Central Metabolic Pathways
pyruvate (3 C) ? acetyl CoA (2 C) CO2 (twice
per glucose)
Transition step
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Central Metabolic Pathways
Transition step
pyruvate (3 C) ? acetyl CoA (2 C) CO2 (twice
per glucose)

• NADH
• precursor metabolite

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Central Metabolic Pathways
TCA cycle (aka Krebs cycle, citric acid cycle)
acetyl CoA (2 C) ? 2 CO2 (twice per glucose)
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Central Metabolic Pathways
TCA cycle (aka Krebs cycle, citric acid cycle)
acetyl CoA (2 C) ? 2 CO2 (twice per glucose)

• ATP

• 3 NADH

• FADH2

• 2 precursor metabolites

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Central Metabolic Pathways
TCA cycle (aka Krebs cycle, citric acid cycle)
acetyl CoA (2 C) ? 2 CO2 (twice per glucose)

• ATP

• 3 NADH

• FADH2

• 2 precursor metabolites

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Central Metabolic Pathways
TCA cycle (aka Krebs cycle, citric acid cycle)
acetyl CoA (2 C) ? 2 CO2 (twice per glucose)

• ATP

• 3 NADH

• FADH2

• 2 precursor metabolites

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Review of central metabolic pathway
Precursor metabolites
ATP (substrate-level phosphorylation)
- carried by NADH, FADH2, NADPH
Biosynthesis Electron transport chain ATP
(oxidative phosphorylation)
Glycolysis Pentose phosphate pathway Krebs cycle
( transition step)
Oxidation of glucose Dehydrogenation to CO2
reducing power (H)
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Precursor Metabolites
Intermediates of catabolism also used in
biosynthesis
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Review
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Respiration
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Electron Transport Chainof mitochondria
TCA cycle Electron carrier get recycled Electron
transport chain Oxidative phosphorylation
Part of figure 3.53
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Electron Transport Chainof mitochondria
Inside of mitochondria
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Electron Transport Chainof mitochondria
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Electron Transport Chainof mitochondria
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Electron Transport Chain
The Mechanics
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Electron Transport Chain
Hydrogen carrier
Electron carrier
Hydrogen carrier
Electron carrier
2H
Hydrogen carrier
2H
Electron carrier
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Electron Transport Chain
Hydrogen carrier
NAD
Regenerates NAD
Electron carrier
Hydrogen carrier
Electron carrier
2H
Hydrogen carrier
2H
Electron carrier
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Electron Transport Chain
Hydrogen carrier
NAD
2H
Electron carrier
2e-
Hydrogen carrier
Electron carrier
2H
Hydrogen carrier
2H
Electron carrier
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Electron Transport Chain
Hydrogen carrier
NAD
2H
Electron carrier
Hydrogen carrier
2e-
2H
Electron carrier
Hydrogen carrier
2H
Electron carrier
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Electron Transport Chain
Hydrogen carrier
NAD
2H
Electron carrier
Hydrogen carrier
2H
Electron carrier
2e-
Hydrogen carrier
2H
Electron carrier
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Electron Transport Chain
Hydrogen carrier
NAD
2H
Electron carrier
Hydrogen carrier
2H
Electron carrier
Hydrogen carrier
2e-
2H
Electron carrier
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Electron Transport Chain
Hydrogen carrier
NAD
2H
Electron carrier
Hydrogen carrier
2H
Electron carrier
Hydrogen carrier
2H
Terminal electron acceptor
Electron carrier
2e-
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Electron Transport Chainof mitochondria
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Electron Transport Chainof E. coli

• Aerobic respiration (shown)
• Anaerobic respiration
• NO3 as a TEA (different ubiquinol oxidase)
• Quinone used provides humans with vitamin K

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Harvesting Energy
The role of electron carriers
C6H12O6 6 O2 ? 6 CO2 6 H2O

• Passed to the electron transport chain (used to
  create the proton motive force) ultimately
  passed to a terminal electron acceptor (such as
  O2, making H2O)

• Used in biosynthesis (to reduce compounds)

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Principles of Metabolism
Synthesizing ATP

• Substrate-level phosphorylation
• Oxidative phosphorylation - the energy of proton
  motive force is harvested chemical energy is
  used to create the proton motive force (involves
  an electron transport chain)

ADP Pi ? ATP
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Harvesting Energy
Energy source versus terminal electron acceptor
Glucose 6 O2 ? 6 CO2 12 H2O
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Overall Maximum Energy Yield
Overall maximum energy yield of aerobic
respiration (ignoring the pentose phosphate
pathway)
Complete oxidation of glucose 4 ATP

• 3 ATP/NADH
• 2 ATP/FADH2

10 NADH 2 FADH2
Electron transport chain (oxidative
phosphorylation)
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Overall Maximum Energy Yield
Overall maximum energy yield of aerobic
respiration (ignoring the pentose phosphate
pathway)
Complete oxidation of glucose 4 ATP

• 3 ATP/NADH
• 2 ATP/FADH2

10 NADH 2 FADH2
Electron transport chain (oxidative
phosphorylation)
38 ATP (maximum theoretical)
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Respiration
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Fermentation

• Used when respiration is not an option
• Lack of TEA
• No electron transport chain
• Oxidation of glucose stops at pyruvate

• Passes electrons from NADH to pyruvate or a
  derivative

The logic

• Oxidizes NADH, generating NAD for use in further
  rounds of glucose breakdown
• Stops short of the transition step and the TCA
  cycle, which together generate 5X more reducing
  power

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Fermentation
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Fermentation
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Review
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Catabolism of Organic Compounds Other than
Glucose (The Elegance of Metabolism)
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Anabolic Pathways

• Synthesis of subunits from precursor metabolites
• Pathways consume ATP, reducing power and
  precursor metabolites
• Macromolecules produces once subunits are
  synthesized

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Principles of Metabolism

• Role of enzymes
• Enzymes facilitate each step of metabolic pathway
• They are proteins acting as chemical catalysts
• Accelerate conversion of substrate to product
• Catalyze reactions by lowering activation energy
• Energy required to initiate a chemical reaction

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Enzymes

• A specific, unique, enzyme catalyzes each
  biochemical reaction
• Enzyme activity can be controlled by a cell
• Enzymes can be exploited medically, industrially
• Enzyme names usually reflect the function and end
  in -ase

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Enzymes
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Enzymes
Allosteric regulation
reversible
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Enzymes
Enzyme inhibition
Competitive inhibition
- Inhibitor/substrate act at the same site
Ex. ? PABA ? ? folic acid ? coenzyme
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Enzymes
Enzyme inhibition
Non-competitive inhibition
- Inhibitor/substrate act at different sites

• Regulation (allosteric)
• Enzyme poisons (example mercury)

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Enzymes
Environmental factors influence enzyme
activity temperature, pH
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Enzymes
Cofactors act in conjunction with certain enzymes
Coenzymes are organic cofactors