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Aerobic Cellular Respiration
• Process that extracts energy from food (mainly glucose, but also proteins and lipids) in the presence of oxygen –obligate aerobes
• The energy that is extracted is used to synthesize ATP• ATP is used to supply energy directly to cells to drive
chemical reactions
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Why Make ATP?
• Referred to as energy currency of the cell• Provide energy for chemical reactions to take place
in our body (cells)
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Mitochondria• Site of cellular respiration (where ATP is made)• Conists of – Outer membrane– Inner membrane– Matrix– Cristae
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Aerobic Cellular Respiration• Divided into 4 stages
1. Glycolysis2. Pyruvate oxidation3. Citric acid cycle4. Electron transport chain and
oxidative phosphorylation• Each Stage involves the
transfer of FREE ENERGY• ATP is produced in two
different ways– Substrate-level phosphorylation– Oxidative phosphorylation
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Aerobic Respiration• Location of each
Stage• Glycolysis– Cytosol
• Pyruvate Oxidation– Mitochondrial matrix
• Citric Acid Cycle– Mitochondrial matrix
• Electron Transport – Inner mitochondrial
membrane
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Glycolysis• Primitive
– Process found in almost all organisms– Both prokaryotes and eukaryotes
• Does not require O₂• Involves
– Soluble enzymes (10 sequential enzyme-catalyzed
reactions) – Oxidation of a 6-carbon sugar glucose
• Produces– 2 molecules of pyruvate (3-
carbon molecule)– 4 ATP and 2 NADH
• Two Phases in which this occurs – Initial energy investment phase – Energy payoff phase
This process is for the conversion of only ONE glucose molecule!!!
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Glycolysis Overview
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Glycolysis Overview • Initial energy investment
phase– 2 ATP are consumed
• Energy payoff phase– 4 ATP produced– 2 NADH molecules are
synthesized
Overall NET reaction; Glucose + 2 ADP + 2 Pi + 2 NAD⁺ → 2
pyruvate + 2 ATP + 2 NADH + 2H⁺• 62 kJ of energy is stored by the
synthesis of 2 ATP molecules • Rest of the free energy is stored in
the 2 pyruvate molecules
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Substrate-Level Phosphorylation• Phosphate groups
are attached to ADP from a substrate forming ATP (enzyme catalyzed reaction)
• ALL ATP molecules are produced this way in Glycolysis
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Pyruvate• Pyruvate can take 2 paths
from this point:1. Aerobic Respiration
(with oxygen) – Pyruvate moves into
mitochondria and ATP is made via Krebs Cycle and Electron Transport Chain
2. Anaerobic Respiration (without oxygen)– Pyruvate stays in
cytoplasm and is converted into lactic acid -Lactic Acid Fermentation
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Pyruvate Oxididation • Remember glycolysis occurs in the cytosol of the cell • The Citric Acid Cycle (next step) occurs in the mitochondrial
matrix• Pyruvate must pass through the inner and outer membrane
of the mitochondrion
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Pyruvate Oxidation• Outer membrane– Pyruvate diffuses across the outer membrane through large pores of
mitochondrion• Inner membrane– Pyruvate-specific membrane carrier is required
• Inside Matrix– Pyruvate is converted into an acetyl group– Acetyl group is bonded to coenzyme A– Produces an acetyl-CoA complex
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Pyruvate OxidationConversion of pyruvate to acetyl-CoAInvolves 2 Reactions• Catalyzed by pyruvate dehydrogenase • Decarboxylation reaction
– Carboxyl group (-COO⁻) of pyruvate is removed – Produces
• CO₂
• Dehydrogenation reaction– 2 electrons and a proton are transferred – Produces
• NADH • H⁺ in solution
Net reaction2 pyruvate + 2 NAD⁺ + 2 CoA → 2 acetyl-CoA + 2 NADH + 2 H⁺ + 2 CO₂
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Pyruvate Oxidation• Acetyl
group reacts with the sulfur atom of coenzyme A
• Acetyl-CoA is the molecule that will start the Citric Acid Cycle
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Citric Acid Cycle• Discovered by– Sir Hans Krebs
(1900-1981)– Consists of 8
enzyme catalyzed reaction
– ALL ATP are produced by substrate-level phosphorylation
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Citric Acid Cycle Overview • 2 molecules of
pyruvate are converted to Acetyl-CoA
• Citric Acid Cycle goes through two turns for every single glucose molecule that is oxidized
1 Turn• Acetyl-CoA + 3 NAD⁺ +
FAD + ADP + Pi → 2 CO₂ + 3 NADH + 3 H⁺ + FADH₂ + ATP + CoA
• ATP is synthesized by substrate level phosphorylation coupled by GTP
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Citric Acid Cycle Overview
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Citric Acid Cycle• ALL of the carbon atoms that make up a glucose
molecule are converted into CO₂– oxidation of pyruvate – acetyl groups
6CO₂
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Oxidation of ONE Glucose Molecule
Total # of NET Molecules Produced
NADH FADH₂ CO₂ ATP
Glycolysis 2 0 0 2
Pyruvate Oxidation
2 0 2 0
Citric Acid Cycle
6 2 4 2
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Electron Transport Chain (Chemiosmosis)• Process that extracts potential energy that is stored in NADH and
FADH₂– These molecules were formed during glycolysis, pyruvate oxidation, and
citric acid cycle– Redox reactions – transfer of electrons
• This energy is used to synthesize additional ATP (A lot more) via oxidative phosphorylation
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The Electron Transport Chain• Occurs on the inner mitochondrial membrane• Facilitates the transfer of electrons from NADH and
FADH₂ to O₂
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The Electron Transport Chain• Composed of • 4 Complexes
– Complex I, NADH dehydrogenase – Complex II, succinate
dehydrogenase– Complex III, cytochrome complex– Complex IV, cytochrome oxidase
• 2 Electron shuttles– Ubiquinone (UQ)
• Hydrophobic molecule – shuttles electrons from complex I and II to complex III
– Cytochrome C (cyt c)• Shuttles electrons from complex III
to complex IV
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The Driving Force Behind Electron Transport • Complexes I, III, IV• Each has a cofactor• Each cofactor has
increasing electronegativity
• Alternate between reduced and oxidized states
• Electrons move towards more electronegative molecules (downstream)
• Final electron acceptor – OXYGEN (most electronegative)
• Pulls electrons from complex IV
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How a Single Oxygen Atom Works (O) • Final electron acceptor
– Removes two electrons from complex IV
– Reacts with 2 H⁺ to produce H₂O
• BUT WE BREATH IN O₂ NOT A SINGLE O
• So for every O₂ molecule – Pulls a total of 4 electrons
through the electron transport chain
– 2 H₂O molecules are produced
• Pulling 4 electrons from complex IV triggers a chain reaction between other complexes!!
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What happens in this chain of reactions?
• Starts with O₂• Pulls electrons
through the chain of complexes
• NADH is least electronegative but contains most free energy
• O₂ has highest electronegativity but contains least amount of free energy
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Proton Gradient• Electron Transport from
NADH or FADH₂ to O₂ does not produce any ATP!!
• What does?• Proton Gradient
– Transport of H⁺ ions across the inner mitochondrial membrane from the matrix into the inter-membrane space
• Creates• Proton-Motive Force
– Chemical gradient (difference in concentrations)
– Electro potential gradient is created (because of the positive charge on Hydrogen atom)
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Proton Gradient
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Chemiosmosis• The ability of
cells to use the proton-motive force to do work
• Synthesizes ATP using electrochemical gradient
• Uses ATP synthase enzyme– ATP is
synthesized using oxidative phosphorylation
34 ATP are Produced!
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Oxidative Phosphorylation• Relies on ATP
synthase– Forms a channel
which H⁺ ions can pass freely
– H⁺ ions cause the synthase to rotate harnessing potential energy to synthesize ATP
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NADH from Glycolysis• NADH produced during glycolysis is in cytosol – Transported into mitochondria via two shuttle
systems• Malate-aspartate shuttle• Glycerol-phosphate shuttle
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NADH and FADH₂• For every NADH that is oxidized
– About 3 ATP are synthesized– 10 NADH x 3 ATP = 30 ATP – NADH is derived from vitamin niacin
• For every FADH₂– About 2 ATP are synthesized– 2 FADH₂ x 2 ATP = 4 ATP– FADH₂ is derived from vitamin riboflavin (B₂)
• Total of 34 ATP synthesized by electron transport chain
• NADH and FADH₂ are involved in REDOX reactions
• Considered Cosubstrates
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Efficiency of Cellular
Respiration
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Efficiency of Cellular Respiration• 38 ATP produced • Hydrolysis of ATP yields 31kJ/mol• 31 kJ/mol x 38 ATP = 1178 kJ/mol• Oxidation of Glucose contains 2870 kJ/mol of
energy
Only 41% of the energy in oxidation of glucose in converted into ATPThe rest is lost as thermal energy
%41%100)/2870(
)/1178(x
molkJ
molkJ
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Cells that need a constant supply of ATP• Brain cells, muscle cells
– Need burst of ATP during periods of activity
• Creatine phosphate pathway– Immediate source of energy – Creatine phosphate splits (high energy)– Donated directly to ADP to re-form ATP– Stored within cell (3 to 5 times more
than ATP)– Provides enough energy for minute
walk or short distance sprint
creatine + ATP → creatine phosphate + ADP
creatine phosphate → creatine + ATP
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Cellular Respiration • Regulated – Feedback inhibition
• Enzyme used – Phosphofructokinase
• Inhibited by– High levels of ATP– High levels of citrate
• Activated by– High levels of ADP– High levels of AMP
• Glucose– Stored as glycogen