Cellular Respiration:
Harvesting Energy from
Carbohydrates and Other
Fuel Molecules
Energy and electrons from glucose
Energy and Electrons from Glucose
• Glucose is the most common fuel for cells
• Other foods are usually converted to glucose
molecules
• Energy is obtained through the oxidation of glucose
Metabolic Pathways
• Chemical transformations are not simple
• Specific enzymes catalyze each step
• All living organisms have similar pathways
• The organelles of eukaryotes house specific sets of
metabolic reactions
• Regulating key enzymes in the pathway controls its
operation
Metabolizing Glucose
• Process traps free energy
• Overall reaction is
• C6H12O6 + 6O2  6CO2 + 6H2O + energy
• Multi-step process
• Energy captured in ATP
• Overall reaction is highly exergonic
An overview
of Cellular
Respiration
ATP Production
QUESTION (1)
Where is the free energy released
during glucose oxidation trapped?
1.
2.
3.
4.
In ADP
In ATP
In cell membranes
In other carbohydrates
Oxidation Reduction Reactions
• Reactions in which one or more electrons (e-)are
transferred between substances
• Reduction – the gain of electrons
• Oxidation – the loss of electrons
• Transfer of electrons = the transfer of hydrogen
atoms
• H = H + + e• Reducing agent
• Oxidizing agent
Oxidation
Reduction
Reactions
NAD is an Energy Carrier
NAD+
NADH
As AH2 is oxidized it
transfers 2 hydrogen
atoms to NAD+
+
H+
NADH + H+ reduces
compound B to BH2
oxidizing NADH
The 2 forms of Nicotinamide
Adenine Dinucleotide
NAD exists in two forms, oxidized (NAD+) and
reduced (NADH)
NAD+ + 2H  NADH + H+
The oxidation of NADH by O2
NADH + H+ + ½ O2  NAD+ + H2O
QUESTION (2)
In redox reactions NAD+ acts as a(n)
1.
2.
3.
4.
proton carrier.
electron carrier.
kinase
enzyme.
In a redox reaction between G3P and NAD+
yielding BPG and NADH+H+, ____ is oxidized
and ____ is reduced.
1.
2.
3.
4.
BPG; NADH
BPG; NAD+
G3P; NADH
G3P; NAD+
The Four
Stages of
Cellular
Respiration
Carbohydrate Catabolism
DG in
Cellular
Respiration
Glycolysis:
Glycolysis:
Glycolysis:
Glycolysis: End Products
• For every molecule of glucose you get:
• 2 molecules of pyruvate
• 2 net ATP molecules
• 2 NADH
QUESTION
The first 5 reactions of glycolysis
require the input of
1.
2.
3.
4.
5.
ADP.
GTP.
FADH.
NAD+.
ATP
The rest of
cellular
respiration
takes place in
the
mitochondria
Pyruvate Oxidation:
1. Pyruvate is oxidized to an acetyl
group and CO2 is released
2. NADH + H+ is formed
3. The acetyl group is combined
with coenzyme A forming
acetyl-CoA
Pyruvate dehydrogenase complex
Pyruvate Oxidation:
• End products:
• 2 molecules of Acetyl-CoA
• 2 NADH
• 2 CO2
• How do we get 2 of each end product?
The Citric Acid Cycle
• Also called the Krebs cycle
• Eight reactions that oxidize the acetyl group to 2
molecules of CO2.
• Free energy is captured by ADP, NAD and FAD
Citric Acid Cycle:
Acetyl-coenzyme A
2C
H2O
H+ +
NADH
NAD+
Oxaloacetate
4C
Citrate
6C
Malate
4C
H2O
Fumarate
4C
Isocitrate
6C
Citric acid
cycle
NAD+
NADH + H+
CO2
a-Ketoglutarate
5C
NAD+
FADH2 FAD
CoA—SH NADH + H+
GDP +
CoA—SH
Pi
GTP
ADP+ Pi ATP
CO2
Citric acid cycle:
Malate is
oxidized to
oxaloacetate
with the
formation of
NADH + H+.
NADH + H+
NAD+
The 2-carbon acetyl
group and 4-carbon
oxaloacetate combine,
forming 6-carbon
citrate.
Citrate is
rearranged
to form its
isomer,
isocitrate.
Fumarate and
water react,
forming malate.
Succinate is oxidized
to fumarate, with the
formation of FADH2.
- Succinyl CoA releases CoA,
becoming succinate
- The energy released converts
GDP to GTP, which in turn
converts ADP to ATP.
Isocitrate is
oxidized to
a-ketoglutarate
a-Ketoglutarate is oxidized
to succinyl CoA
QUESTION
How many rounds of TCA cycle are
required per glucose molecule?
1.
2.
3.
4.
5.
6.
1
2
3
4
5
6
Which two molecules combine to
start TCA cycle?
1.
2.
3.
4.
Citrate and succinate
Glucose and pyruvate
Acetyl-CoA and glucose
Acetyl-CoA and oxaloacetate
Quick Review:
• Oxidation-reduction reactions
• Electron carriers
• Cell respiration: conversion of glucose to CO2 and H2O with
the synthesis of ATP
• Substrate level phosphorylation and oxidative phosphorylation
• Glycolysis
• Pyruvate oxidation
• Citric Acid Cycle
TCA Cycle an Overview
• TCA cycle operates twice for every glucose molecule
that enters glycolysis
• Takes place in the mitochondrial matrix
• The end products are:
• 4 molecules of CO2
• 6 molecules of NADH (3 for each pyruvate)
• 2 molecules of FADH2 (1 for each pyruvate)
• 2 molecules of ATP (1 for each pyruvate)
The Electron Transport Chain
(Respiratory Chain)
• The electrons removed from glucose are transferred to
NAD and FAD
• 2 NADH + H+ from glycolysis
• 2 NADH + H+ from Pyruvate oxidation
• 6 NADH + H + from TCA cycle
• 2 FADH2 from TCA cycle
• Electrons from NADH and FADH2 now enter the electron
transport chain
• A series of electron carriers in the inner mito. membrane
• Electrons are shuttled from one electron carrier to another
The Electron Transport Chain
• The transfer of electrons drives the pumping of
protons across the inner mito. membrane
• Transfer of electrons is exergonic
• [H+] in the inner membrane space > [H+] in the matrix
• Proton-motive force – the potential energy of the protons
• The protons diffuse back across the membrane
through a proton channel called ATP synthase
• Coupled to ATP synthesis
• Oxidative phosphorylation
Mitochondrion
The Electron Transport
Chain (ETC) is located in
the inner mitochondrial
membrane
Cytoplasm
Outer
mitochondrial
membrane
Intermembrane
space
Inner
mitochondrial
membrane
Matrix of mitochondrion
Electron Transport Chain:
Electron Transport Chain:
Complex I
Complex III
Complex II
Complex IV
Electron Transport Chain:
• Energy is released as the electrons pass from carrier to carrier
• Complexes I, III and IV also function as proton pumps and pump
protons into the inner membrane space
ATP
Synthase
Total Energy yields
• Oxidation of NADH and FADH2 by the electron transport chain
produces ATP
• 2.5 ATP for each NADH
• 1.5 ATP for each FADH2
How much ATP is produced?
glycolysis:
2 ATP
2 ATP
2 NADH
5 ATP
pyruvate oxidation 2 NADH
5 ATP
TCA cycle
2 ATP
2 ATP
6 NADH
15 ATP
2 FADH2
3 ATP
32 ATP***
*** 2 ATP are used to transport NADH from glycolysis
across the inner mito. membrane
QUESTION (3)
What drives ATP synthesis?
1. Diffusion of protons down a
concentration gradient
2. Active transport of protons
3. Active transport of electrons
4. Facilitate transport of glucose
What is the role of oxygen in the
electron transport chain?
1. It combines with NAD+
2. It is the terminal electron
acceptor
3. It binds to ATP
Certain drugs make the mitochondrial
membrane more permeable to protons. How
would this affect ATP synthesis?
1. ATP synthesis would be inhibited.
2. ATP synthesis would be
stimulated.
3. ATP synthesis would be
unaffected.
ATP synthesis is reversible
ATP ↔ ADP + Pi + free energy
•
•
ATP synthase can also work as an ATPase
Why is synthesis preferred?
1. ATP leaves the mitochondrion as soon as it is made
2. The electron transport chain maintains the H+
gradient
Anaerobic metabolism: Fermentation
• Under anaerobic conditions
cells can still make a small
amount of ATP
• Lactic acid or ethanol
fermentation
• Needed to keep glycolysis
running
Anaerobic metabolism: Fermentation
• Ethanol fermentation used by
plants and fungi
• Produces CO2, NAD+ and
ethanol
QUESTION (1)
Why is fermentation necessary
under anaerobic conditions?
1.
2.
3.
4.
To decrease NAD+ and increase NADH
To increase ATP and increase NADH
To increase NAD+ and decrease NADH
To keep the electron transport chain
running
Metabolic Integration
What happens if there is more glucose than the cells need?
How are carbohydrates, lipids and proteins broken down?
Do they contribute to ATP synthesis?
What do cells do with excess glucose?
• Stored as
• Glycogen in animals
• Starch in plants
• Large branched polymers
of glucose
How Other Sugars Contribute to Glycolysis
• The carbohydrates in our diet are digested to a variety of
sugars
• Sugars besides glucose are converted to intermediates of
glycolysis
How do we convert
different foods into
energy?
Meal: Hamburger on a
bun
• Carbohydrates
• Lipids
• proteins
Lipid Metabolism
• Good source of energy
because of all the C-C and C-H
bonds
• 1st broken down into glycerol
and fatty acids
• 2nd the fatty acid molecules
are processed by b-oxidation
Regulation of Metabolism
• Level of ATP in a cell is an indicator
of how much energy a cell has
available
• ATP high  ATP synthesis is slowed
• ATP low  ATP synthesis speeds up
• Key enzymes throughout the
pathway are regulated
• Phosphofructokinase-1
Phosphofructokinase-1
Activation
ATP levels are low.
ADP
Inhibition
ATP or citrate levels are high.
Allosteric
controls
Citrate
ATP
AMP
–
+
Phosphofructokinase-1
Fructose 6-phosphate
When ATP levels are low,
PFK-1 is activated,
allowing
glycolysis to continue.
Fructose 1,6bisphosphate
Glycolysis
Fructose 6-phosphate Fructose 1,6bisphosphate
When ATP or citrate levels
are high, PFK-1 is inhibited,
and glycolysis slows.
Glycolysis
Phosphofructokinase-1
Activation
ATP levels are low.
ADP
Inhibition
ATP or citrate levels are high.
Allosteric
controls
Citrate
ATP
AMP
–
+
Phosphofructokinase-1
Fructose 6-phosphate
When ATP levels are low,
PFK-1 is activated,
allowing
glycolysis to continue.
Fructose 1,6bisphosphate
Glycolysis
Fructose 6-phosphate Fructose 1,6bisphosphate
When ATP or citrate levels
are high, PFK-1 is inhibited,
and glycolysis slows.
Glycolysis