Metabolic Pathways

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Metabolic Pathways
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Metabolic Pathways
This section will cover the cellular pathways
that produce ATP from glucose and other
nutrients. (Chapter 7)
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Metabolic Pathways

• There is potential energy in covalent bonds.
• But where does the energy come from?

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Metabolic Pathways
The disorder of the system has decreased. or The
entropy has decreased. ?S lt 0
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Metabolic Pathways
Since ?G - T?S Then If ?Slt0, ?Ggt0
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?Ggt0 or the potential energy has increased
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Metabolic Pathways

• There is potential energy in covalent bonds.
• But where does the energy come from?

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Metabolic Pathways
The energy is stored in the electrons.
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Metabolic Pathways
A covalent bond is the sharing of 2 electrons.
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Metabolic Pathways
The electrons have a certain degree of
entropy. Because the orbitals overlap in a
covalent bond, there is less entropy.
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Metabolic Pathways
?Slt0 then ?Ggt0 or
the potential energy has
increased.
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Bond Energy C-N 308 kJ/mol C-C 348 C-O 360 H-O
366 C-H 413 H-H 436
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Metabolic Pathways
Strong bonds have low chemical energy
and
weak bonds have high
chemical energy.
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Metabolic Pathways

• REDOX reactions
• oxidation - reduction reactions

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Metabolic Pathways

• In a REDOX reaction
  electrons are transferred
  from one atom to another.
• This transfer of electrons is a transfer of
  energy.

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Metabolic Pathways

• Transferring electrons from one molecule to
  another is a means by which energy can be
  transferred from one molecule to another.

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Metabolic Pathways

• In the cell, glucose is metabolized to
  carbon dioxide, water, and energy.
• C6H12O6 6 O2 ? 6 CO2 6 H2O energy
• The energy yielding steps in the metabolism of
  glucose are REDOX reactions.

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Metabolic Pathways

• REDOX reactions are chemical reactions in which
  one of the reactants becomes oxidized (loses an
  electron) and the other
  reactant becomes reduced
  (gains an electron).

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Metabolic Pathways

• Oxidation-Reduction reactions or Redox
  reactions are 2
  reactions that always occur together.

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Metabolic Pathways

• Oxidation is LOSS of electrons.

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Metabolic Pathways

• This loss of electrons can be outright to form an
  ion or the electrons may be shared with a
  substance that has a greater affinity for the
  electrons, such as oxygen.

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Metabolic Pathways

• Most oxidation reactions are associated with the
  liberation of energy.

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Metabolic Pathways

• Reduction is the GAIN of electrons.

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Metabolic Pathways

• All reductions are accompanied by an oxidation.

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Metabolic Pathways
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Metabolic Pathways

• An oxidizing agent is the reactant that accepts
  an electron or a hydrogen atom.
• A reducing agent is the reactant that donates an
  electron or a hydrogen atom.

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Metabolic Pathways
Reducing Agent
Oxidizing Agent
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Metabolic Pathways
C6H12O6 6 O2 ? 6 CO2 6 H2O energy

• During the metabolism of glucose, glucose donates
  electrons.
• Therefore, glucose is oxidized.

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Metabolic Pathways
C6H12O6 6 O2 ? 6 CO2 6 H2O energy

• Oxygen accepts electrons.
• Therefore, oxygen is reduced.

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Metabolic Pathways
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Metabolic Pathways

• Whenever one molecule reduced, another is
  oxidized.
• In this process, energy is transferred as the
  electron is transferred from molecule to
  molecule.
• This energy will ultimately be captured in ATP.
• ADP Pi ? ATP

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Metabolic Pathways
C6H12O6 6 O2 ? 6 CO2 6 H2O energy

• However, during glucose oxidation, the
  electrons of glucose are first passed to an
  electron carrier.

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Metabolic Pathways

• The cell has 2 electron carriers
• NAD or FAD.

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Metabolic Pathways

• NAD and FAD accept the electrons from glucose
  and transfers them to the mitochondria, where ATP
  is synthesized.

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Metabolic Pathways

• The coenzyme
• nicotinamide adenine dinucleotide (NAD)
• is an essential electron carrier
  in cellular redox reactions.

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NAD
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NADP
NADP is usually used for anabolic reactions.
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Metabolic Pathways

• NAD can be oxidized or reduced.
• NAD exists in an oxidized form NAD
• and a reduced form NADH H.

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Metabolic Pathways

• NAD accepts 2 electrons 1 hydrogen ion (H)
• from 2 hydrogen atoms.

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Metabolic Pathways

• NADH H NAD energy

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Metabolic Pathways

• The reduction of NAD requires an input of energy
  (endergonic)
• NAD 2H energy ? NADH H

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Metabolic Pathways

• The oxidation of NADH H is exergonic
• NADH H ? NAD energy

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Energy is required.
Energy is required.
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Energy is released.
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Energy is released.
Energy is required.
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Metabolic Pathways

• Flavin adenine dinucleotide (FAD) is another
  electron transporter in cellular redox reactions
• FAD 2H FADH2

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Metabolic Pathways
In principle, reactions can run in both
directions.
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Metabolic Pathways

• The direction each reaction goes depends on the
  concentration of products versus substrates.

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Metabolic Pathways

• If there are more substrates,
  the reaction will move forward.
• If there are more products,
  the reaction will move in reverse.

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Metabolic Pathways

• At some concentration of reactants and products,
  the forward rate will equal
  the reverse rate.

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Metabolic Pathways
When the rate of the forward reaction is equal to
the rate of
the reverse reaction, the reaction is in
equilibrium.
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Metabolic Pathways
If we add 100 mol G-6-P to the reactants (the
left side of the equation), the reaction will
proceed to the formation of more products.
190 mol G-6-P 10 mol G-1-P
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Metabolic Pathways
If we add 100 mol G-1-P to the products (the
right side of the equation), the reaction will
proceed to the formation of more reactants.
190 mol G-6-P 10 mol G-1-P
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Metabolic Pathways
Metabolic pathways are a series of chemical
reactions where the product of the first reaction
serves as the substrate for the second reaction.
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Metabolic Pathways
The addition of A will push the reaction to the
right producing B and since B is a substrate for
the next reaction, the reaction continue toward
the production of C and so on to produce D.
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Metabolic Pathways
Each reaction is catalyzed by a separate enzyme.
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Metabolic Pathways
The activity of each metabolic pathway can be
regulated by the activities of key
enzymes.
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Metabolic Pathways
The production of D can be regulated by limiting
the availability of B or

by controlling the activity of the enzymes
catalyzing the various reactions.
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Metabolic Pathways

• Metabolic pathways are similar
  in all organisms.

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Metabolic Pathways
Glycolysis,
the Krebs cycle
and oxidative
phosphorylation are
metabolic pathways
in the aerobic respiration of glucose.
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D-Glucose aka dextrose
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Metabolic Pathways

• In eukaryotes, many metabolic pathways are
  compartmentalized in organelles.

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Metabolic Pathways
The sugar glucose (C6H12O6) is the most common
form of energy molecule. The energy in glucose
is stored in the chemical bonds.
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Metabolic Pathways
When burned in a flame, glucose releases carbon
dioxide, water and heat (energy). C6H12O6 6 O2
? 6 CO2 6 H2O energy The same equation
applies for the biological metabolism of glucose.
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Metabolic Pathways
The chemical bonds in glucose are broken to
release energy (exergonic).
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For the complete oxidation of glucose ?G 686
kcal/mol. About half of the energy is captured
in the endergonic formation of ATP. ADP Pi ?
ATP ?G 7.3 kcal/mol.
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Glycolysis

• Complete aerobic metabolism of 1
  glucose molecule will produce 36 ATP.

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Glycolysis

• Glycolysis begins glucose metabolism in all
  cells.

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Glycolysis

• Glycolysis occurs in the cytoplasm.
• A 6-carbon (6C) glucose molecule is
  converted to
  two 3-carbon (3C) pyruvate molecules.
• This produces some usable energy. (2
  ATP molecules are generated)

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Glucose
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Glycolysis
Glucose

2 Pyruvate
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Pyruvate
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Glycolysis
Glucose

2 Pyruvate
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Glucose

2 Pyruvate 2 NADH H 2 ATP
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Glycolysis

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

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Glycolysis

• The energy-investing reactions of glycolysis
• In separate reactions,
  glucose is phosphorylated on
  carbon 6 and carbon 1
• to form fructose 1,6-bisphosphate
• and 2 ATP are hydrolyzed to ADP Pi.

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This is the rate-limiting step
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Glucose
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Glucose 6-phosphate
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Glucose 6-phosphate
Fructose 6-phosphate
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Fructose 6-phosphate
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Fructose 1,6 bisphosphate
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Glycolysis

• The enzyme aldolase splits the molecule into two
  3-C molecules that become
• glyceraldehyde 3-phosphate (G3P).

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H
H
O
C
C
O
H
Glyceraldehyde 3-phosphate (G3P)
Dihydroxyacetone phosphate (DAP)
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Fructose 1,6 bisphosphate
Aldolase
2x
Glyceraldehyde 3-phosphate (G3P)
Dihydroxyacetone phosphate (DAP)
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isomerase
Glyceraldehyde 3-phosphate (G3P)
Dihydroxyacetone phosphate (DAP)
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1 Glucose produces 2 G3P
isomerase
Glyceraldehyde 3-phosphate (G3P)
Dihydroxyacetone phosphate (DAP)
2x
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Pyruvate
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2 NAD 2 NADH and 4 ADP 4 ATP
Pyruvate
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Glycolysis

• The remaining reactions harvest energy.
• The first reaction (an oxidation) releases free
  energy that is used to make
• two molecules of NADH H,
• one for each of the
• two Glyceraldehyde 3-phosphate molecules.

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Glycolysis
For each glucose molecule 2 pyruvate molecules
are generated. In addition, for each glucose
molecule 2 NAD are reduced to NADH and 4 ATP
molecules are generated from ADP.
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Glycolysis

• The generation of ATP in this part of the pathway
  is called substrate-level phosphorylation.
• In substrate level phosphorylation, a phosphate
  group (P) is transferred from one molecule to ADP
  to form ATP.

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Glycolysis

• Main steps in glycolysis
• One glucose molecule (6C) is converted to two
  pyruvate molecules (3C).
• 2 ATP are used and 4 ATP are generated.
• There is a net gain of 2 ATP
  and
• 2 NAD are reduced to NADH.

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Glycolysis

• The process takes place in the cytoplasm.

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Glycolysis

• The rate limiting enzyme is
• phosphofructo-kinase (PFK).

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This is the rate-limiting step
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Glycolysis

• The final product of glycolysis is
  two 3-carbon molecules of pyruvate.

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PYRUVATE OXIDATION
The next step in the oxidation of glucose occurs
in the mitochondria
and is call pyruvate
oxidation.
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PYRUVATE OXIDATION

• Pyruvate oxidation
• Pyruvate (3C) is oxidized to
• acetyl CoA (2C) and a CO2 molecule.
• One NAD is reduced to NADH H during this
  reaction for each pyruvate.

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Pyruvate
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PYRUVATE OXIDATION
Pyruvate
Acetyl-CoA CO2
CoA

CH3
C
CO2
Acetyl-CoA
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PYRUVATE OXIDATION
Pyruvate
Acetyl-CoA CO2
CoA

CH3
C
CO2
Acetyl-CoA
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PYRUVATE OXIDATION
Pyruvate
Acetyl-CoA CO2
CoA

CH3
C

NADH H
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PYRUVATE OXIDATION
Pyruvate
Acetyl-CoA CO2
CoA

CH3
C

NADH H
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PYRUVATE OXIDATION

• Acetyl CoA is the only molecule that can enter at
  the start of the
  Krebs cycle.

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the Krebs cycle
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PYRUVATE OXIDATION
Pyruvate
Acetyl-CoA CO2
CoA

CH3
C

NADH H
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PYRUVATE OXIDATION
Pyruvate
pyruvate dehydrogenase
Acetyl-CoA CO2
CoA

CH3
C

NADH H
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PYRUVATE OXIDATION

• Pyruvate oxidation is a multistep reaction
  catalyzed by an enzyme complex
  (pyruvate dehydrogenase) attached to the
  inner mitochondrial membrane.

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PYRUVATE OXIDATION
Pyruvate
pyruvate dehydrogenase
Acetyl-CoA CO2


NADH H
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Acetyl CoA
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Krebs Cycle

• For each turn of the cycle (for each
  acetyl-CoA), the following
  molecules are generated
• 3 NADH H
• 1 ATP
• 1 FADH2
• 2 CO2

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Krebs Cycle

• For 1 glucose molecule,
  2 acetyl CoA molecules are generated.
• or 1 glucose molecule will generate
• 6 NADH H
• 2 ATP
• 2 FADH2
• 4 CO2

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Acetyl CoA
This is the rate-limiting step
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Acetyl CoA
NADH
This is the rate-limiting step
NADH CO2
FADH2
NADH CO2
ATP
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Krebs Cycle
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Krebs Cycle

• The citric acid (Krebs) cycle begins when the two
  carbons from the acetyl-coA are added to
  oxaloacetate (a 4-C molecule) to generate
  citrate (a 6-C molecule).

1
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Krebs Cycle

• A series of reactions oxidize 2
  carbons from the citrate producing 2 CO2
  molecules.

2
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Krebs Cycle

• A series of molecular rearrangements,
  regenerates oxaloacetate,
  which can be used for the next cycle.

3
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Acetyl CoA
4 carbon molecule
Krebs Cycle

1
6 carbon molecule
3
5 carbon molecule CO2
NADH
2
4 carbon molecule CO2
NADH
ATP
NADH FADH2
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Krebs Cycle
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Krebs Cycle

• The Krebs Cycle
• occurs in the mitochondria.

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Krebs Cycle

• Isocitrate dehydrogenase is the rate limiting
  enzyme.

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Krebs Cycle
Isocitrate dehydrogenase
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Krebs Cycle

• Substrate level phosphorylation is used to
  generate ATP.

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Acetyl CoA
This is the rate-limiting step
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Krebs Cycle

• For each turn of the Krebs Cycle
• 3 NADH
• 1 FADH2
• 1 ATP are generated.

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Krebs Cycle
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Krebs Cycle

• For each glucose molecule the Krebs Cycle turns
  twice, generating
• 6 NADH
• 2 FADH2
• 2 ATP.

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Electron Transport Chain

• Electron transport chain
• The NADH and FADH2 formed in the previous
  steps are oxidized to generate ATP.

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Electron Transport Chain

• 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 (aka
  proton-motive force).

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Electron Transport Chain

• This process occurs in the mitochondria.
• The respiratory chain consists of four large
  protein/enzyme complexes bound to the inner
  mitochondrial membrane, plus cytochrome c and
  ubiquinone (Q).

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Electron Transport Chain

• The four enzyme complexes are
• NADH-Q reductase
• Succinate dehydrogenase
• Cytochrome c reductase
• Cytochrome c oxidase.

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Electron Transport Chain

• NADH H passes its electrons to the NADH-Q
  reductase protein complex.
• The NADH-Q reductase passes the electrons on to
  ubiquinone (Q), forming QH2.
• Ubiquinone is also called Co-enzyme Q10
  (CoQ10).

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Electron Transport Chain

• The QH2 passes electrons to cytochrome c
  reductase complex which in turn passes them to
  the
• cytochrome c oxidase complex.
• Cytochrome c oxidase is the rate limiting enzyme.

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Electron Transport Chain

• The electrons are passed to molecular
  oxygen (O2)
  the final electron acceptor.
• Reduced oxygen unites with two hydrogen ions to
  form water.

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Electron Transport Chain

• As electrons pass through the respiratory chain,
  the energy is used to pump protons by active
  transport into the intermembrane space,
  creating a proton gradient.
• The potential energy generated by this proton
  gradient is called the proton-motive force.

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Electron Transport Chain

• This transport results in the production of both
  a concentration and charge
  gradient across the inner
  mitochondrial membrane.
• There is more H (more positive charge) in the
  intermembrane space than in the matrix.

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Electron Transport Chain

• For every NADH oxidized, enough energy is
  released to transport 3 PROTONS.

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Electron Transport Chain

• Because FADH2 donates its electrons to
  succinate dehydrogenase
• For every FADH2 oxidized, enough energy is
  released to transport 2 PROTONS.

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Oxidative Phosphorylation

• 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 stoichiometry of transport for the pathway
from NADH to O2 is 10 H/2e-.
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Ironically, certain cold-adapted animals,
hibernating animals, and newborn animals generate
large amounts of heat by uncoupling oxidative
phosphorylation. Adipose tissue in these
organisms contains so many mitochondria that it
is called brown adipose tissue for the color
imparted by the mitochondria. The inner membrane
of brown adipose tissue mitochondria contains an
endogenous protein called thermogenin (literally,
"heat maker"), or uncoupling protein, that
creates a passive proton channel through which
protons flow from the cytosol to the matrix.
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Certain plants also use the heat of uncoupled
proton transport for a special purpose. Skunk
cabbage and related plants contain floral spikes
that are maintained as much as 20 degrees above
ambient temperature in this way. The warmth of
the spikes serves to vaporize odiferous
molecules, which attract insects that fertilize
the flowers.
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The P/O ratio is the number of molecules of ATP
formed in oxidative phosphorylation per two
electrons flowing through a defined segment of
the electron transport chain.
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In spite of intense study of this ratio, its
actual value remains a matter of contention. If
we accept the value of 10 H transported out of
the matrix per 2 e- passed from NADH to O2
through the electron transport chain, and also
agree (as above) that 4 H are transported into
the matrix per ATP synthesized (and
translocated), then the mitochondrial P/O ratio
is 10/4, or 2.5, for the case of electrons
entering the electron transport chain as NADH.
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This is somewhat lower than earlier estimates,
which placed the P/O ratio at 3 for mitochondrial
oxidation of NADH. For the portion of the chain
from succinate to O2, the H/2 e- ratio is 6 (as
noted above), and the P/O ratio in this case
would be 6/4, or 1.5 earlier estimates placed
this number at 2.
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The consensus of experimental measurements of P/O
ratios for these two cases has been closer to the
more modern values of 2.5 and 1.5. Many chemists
and biochemists, accustomed to the integral
stoichiometries of chemical and metabolic
reactions, have been reluctant to accept the
notion of nonintegral P/O ratios. At some
point, as we learn more about these complex
coupled processes, it may be necessary to
reassess the numbers.
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Hypothetically speaking, how much energy does a
eukaryotic cell extract from the glucose
molecule? Taking a value of 50 kJ/mol for the
hydrolysis of ATP under cellular conditions
(Chapter 3), the production of 32 ATP per glucose
oxidized yields 1600 kJ/mol of glucose . The
cellular oxidation (combustion) of glucose yields
DG -2937 kJ/mol. We can calculate an efficiency
for the pathways of glycolysis, the TCA cycle,
electron transport, and oxidative phosphorylation
of This is the result of approximately 3.5
billion years of evolution.
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Oxidative phosphorylation
is the production of ATP
using energy derived from
the transfer of electrons in an electron
transport system and occurs by chemiosmosis.
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The chemiosmotic theory explains the functioning
of electron transport chains. According to this
theory, electrons are transported down an
electron transport system through a series of
oxidation-reduction reactions releases energy.
The energy of the electrons allows certain
carriers in the chain to transport hydrogen ions
(H or protons) across a membrane.
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As the hydrogen ions accumulate on one side of a
membrane, the concentration of hydrogen ions
creates an electrochemical gradient or potential
difference (voltage) across the membrane. (The
fluid on the side of the membrane where the
protons accumulate acquires a positive charge
the fluid on the opposite side of the membrane is
left with a negative charge.) The energized state
of the membrane as a result of this charge
separation is called proton motive force.
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In prokaryotic cells,
the protons are transported
from the cytoplasm of the bacterium across the
cytoplasmic membrane to the periplasmic space
located between the cytoplasmic membrane and the
cell wall.
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Oxidative Phosphorylation

• Oxidative Phosphorylation is the production of
  ATP using energy derived from the transfer of
  electrons in an electron transport system and
  occurs by chemiosmosis.

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Oxidative Phosphorylation

• The potential energy from the proton-motive
  force is harnessed by ATP synthase to
  synthesize ATP from ADP Pi.
• As each proton diffuses through the ATP synthase,
  
• ADP Pi is converted to ATP.

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Oxidative Phosphorylation

• 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 H by the
  electron transport chain.

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Oxidative Phosphorylation

• For every NADH oxidized, enough energy is
  released to drive the formation of 3 ATP.

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Oxidative Phosphorylation

• For every FADH2 oxidized, enough energy is
  released to drive the formation of 2 ATP.
• This is because FADH2 donates its electrons to
  succinate dehydrogenase.

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Metabolic Pathways

• ATP generated from 1 Glucose molecule
• ATP NADH FADH2
• Glycolysis 2 2
• Pyruvate
• oxidation 2
• Krebs cycle 2 6
  2
• Total ATP 4 30
  4 38

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Metabolic Pathways

• Actually 36 ATP are generated because the NADH
  generated in glycolysis cannot enter the
  mitochondria.
• Their electrons are passed across the membrane to
  an FADH2 molecule.
  FADH2 only yields 2 ATP.

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Metabolic Pathways

• ATP generated from 1 Glucose molecule
• ATP NADH FADH2
• Glycolysis 2 2
• Pyruvate
• oxidation 2
• Krebs cycle 2 6
  2
• Total ATP 4 28
  4 36

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Metabolic Pathways
Cyanide inhibits cytochrome
c oxidase (complex IV).
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Statins
CoQ10
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Metabolic Pathways

• Without 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.
• At this point the respiratory chain stops.

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Metabolic Pathways

• NAD and FAD are not regenerated from their
  reduced form.
• Because glycolysis requires NAD, glycolysis
  stops.
• Because Pyruvate Oxidation requires NAD,
  Pyruvate Oxidation stops.
• Likewise, the Krebs cycle stops.

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Metabolic Pathways
Some cells under anaerobic conditions continue
glycolysis and produce a limited amount of ATP.
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FERMENTATION
Pyruvate
O-
Ethanol
Lactate
CO2
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FERMENTATION

• When O2 is not available, glycolysis is followed
  by fermentation.
• Fermentation uses NADH H to reduce pyruvate,
  and consequently NAD is regenerated.

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FERMENTATION

• Fermentation occurs in the cytoplasm.
• Pyruvate is converted to lactic acid or ethanol.
• This is an anaerobic process,
  it does not involve O2.
• The breakdown of glucose is incomplete. Only
  2 ATP are produced.

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FERMENTATION

• In lactic acid fermentation, an enzyme,
  lactate dehydrogenase, uses the reducing power of
  NADH H to convert pyruvate
  into lactate (lactic acid).

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Pyruvate NADH
Ethanol NAD
Lactate NAD
CO2
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FERMENTATION

• 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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FERMENTATION

• NAD is replenished in the process.
• This allows glycolysis to proceed.
• However, only 2 ATP molecules are formed from
  glucose in this process.

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FERMENTATION

• Anaerobic respiration of glucose 2 ATP
• Aerobic respiration of glucose 36 ATP

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FERMENTATION

• 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.
• Yeast are efficient at doing alcoholic
  fermentation.

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FERMENTATION

• 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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Metabolic Pathways

• Polysaccharides (glycogen) are hydrolyzed into
  glucose which passes on to glycolysis.

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Metabolic Pathways

• Lipids (triglycerides) are broken down by the
  enzyme lipase into the three fatty acids and
  glycerol.
• Glycerol ( a 3 carbon sugar-alcohol) is converted
  to an intermediate in glycolysis an enters that
  pathway.
• The Fatty Acids are broken down by a process
  called beta oxidation.

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Metabolic Pathways

• Beta oxidation
• Fatty Acids are broken down 2 carbons at a time
  to yield acetyl-coA.
• The acetyl-coA enters the Krebs cycle.

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Metabolic Pathways

• Proteins are hydrolyzed into amino acids
• Proteins are deaminated (amino group is removed)
  or transaminated (amino group is transferred to
  another molecule).
• The remaining molecule is usually an intermediate
  found in glycolysis or the Krebs cycle.

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Metabolic Pathways

• When food supplies are insufficient
• Some cells will use glycogen stores as a source
  for glucose.
• Next, the cell will use fats (triglycerides).
• Finally, the cell will breakdown proteins to
  amino acids, which are used as an energy source.

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Metabolic Pathways

• REGULATION
• 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
  (metabolic homeostasis).

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Metabolic 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.
• i.e. if there is no ATP, glucose is used for
  energy, if there is plenty of ATP, glucose is
  used to synthesize molecules .usually fat!

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Metabolic 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.

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Metabolic Pathways

• The main control point in glycolysis is the
  enzyme phosphofructokinase.
• Phosphofructokinase is inhibited by ATP
  and
  activated by ADP and AMP.

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Metabolic Pathways

• The main control point of the Krebs cycle is the
  enzyme isocitrate dehydrogenase, which converts
  isocitrate to ?-ketoglutarate.
• Isocitrate dehydrogenase is
  inhibited by NADH H and ATP
  and
  activated by NAD and ADP.

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Metabolic Pathways

• 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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