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Cellular Respiration
Chapter 9:
The Process
Objectives
• Understand that cellular respiration is a series
of coupled metabolic processes
• Describe the role of ATP, NAD+ and FAD in
coupled reactions
• Know the start and end products of each
reaction
• Know the kind and quantity of energy
produced by each reaction
• Understand the role of dehydrogenase,
kinase and isomerase enzymes
• Explain how ATP production is controlled
during glycolysis, transition reaction, and
Krebs cycle
Objectives continued
• Understand the process of chemiosmosis
• Explain how the “slide” of electrons down the electron
transport chain is coupled to the production of ATP
by chemiosmosis
• Understand the difference between substrate-level
phosphorylation and oxidative phosphorylation
• Describe the fate of pyruvate during fermentation
• Understand how food molecules other than glucose
can be oxidized to make ATP
• Understand how anabolic synthesis of carbohydrate
metabolism can generate the building blocks of other
macromolecules
Overview
C6H1206 + 6O26CO2 +6H20 + ENERGY
• Aerobic cellular
respiration has 4 steps
– Glycolysis
• in cytosol
– Transition reaction
(Pyruvate Processing)
• at mitochondrial
membrane
– Kreb’s cycle
• in mitochondrial matrix
– Electron Transport
Chain
• at inner membrane of
mitochondria
• Start with
glucose
(C6H1206)
• End product
is 2x
Pyruvate
2(C3H4O3)
• Some steps
are
endergonic
while others
are exergonic
Glycolysis
1 First obstacle
– make glucose reactive
• Increase free energy of
glucose by
phosphorylation by ATP
2 Rearrange molecule
3 Increase free energy of
glucose by
phosphorylation with ATP
 phosphofructokinase is an
allosteric enzyme that
controls the rate of
glycolysis
• Result in reactive molecule
4 Now that our 6C sugar (fructose 1,6-biphosphate) is ready to
react, aldolase cleaves it into 2(3C) molecules that are isomers
(what kind) of each other.
 5 Isomerase converts the unusable Dihydroxyacetone
phosphate into Glyceraldehyde phosphate
6 Each glyceraldehyde phosphate is acted on by the enzyme Triose phosphate
dehydrogenase that oxidized the sugar by reducing NAD+ and sequentially
adding inorganic phosphate to the sugar
7 A molecule of ATP is made from each 1,3-biphosphoglycerate as the phosphate
added in step 6 is transferred to ADP
8 The molecule is reorganized through the relocation of the phosphate group
9 Enolase makes an enol (C=C-O) through the removal of
water resulting in an unstable molecule (prone to change)
10 Terminal step in glycolysis results in the formation of
Pyruvate as the enzyme Pyruvate kinase transfers the
phosphate group of phosphoenolpyruvate to ADP
forming ATP
Glycolysis Summarized
•
•
•
•
Glucose converted into 2 pyruvate
Energy requiring and energy releasing steps
Energy net yield is 2ATP and 2NADH
Enzymes involved at each step
– Kinase: conversion of ATP to ADP or ADP to ATP
– Dehydrogenase: reduces NAD+ to NADH while
oxidizing sugar
– Isomerase/mutase: keep reactions moving forward
through isomer formation
• Regulated by phosphofructokinase activity (step
3) and the rate of isomer formation of
glyceraldehyde phosphate (step 5)
Regulation of Glycolysis
• Phosphofructokinase is regulated by allosteric means where:
– AMP activate enzyme
– Citrate (high energy molecule of the Krebs cycle) inhibits enzyme
• Also regulated by feedback inhibition
• Isomerase is regulated by enzyme
concentration and substrate availability
Another View of the Feedback
Mechanisms for Glycolysis
• Feedback inhibition
– ample product switches off
product
• Regulation of enzyme
activity
• Allosteric regulation of
phosphofructokinase
– AMP activate enzyme
– Citrate inhibits enzyme
Mitochondria
Transition reaction
• at mitochondrial
membrane
Kreb’s cycle
• in mitochondrial
matrix
Electron Transport
Chain
• Across the inner
membrane of
mitochondria
Transition Reaction
• Pyruvate is converted into Acetyl-CoA as it is
transported into the mitochondrion from the
cytosol
• NAD+ converted into NADH
• CO2 produced during reaction
Krebs Cycle
• Each molecule of
Acetyl- CoA enters the
Krebs cycle
• the 2C of acetyl-CoA
are exchanged for
2C in oxaloacetate
• Each turn of the cycle
produces
–
–
–
–
3 NADH
1FADH2
1ATP
2CO2
1 Acetyl CoA enters the kreb’s
cycle by attaching to a 4
carbon sugar (Oxaloacetate)
forming a six carbon sugar
(Citrate)
2 An isomer of citrate is created
through
condensation/hydrolysis
reactions resulting in isocitrate
3 Isocitrate loses CO2 forming
-ketoglutarate as oxidation of
the compound occurs NADH
is formed
4 -ketoglutarate (C5) is
converted to Succinyl CoA
(C4). Along the way, CO2 is
released, and NAD+ is reduced
5 Succinyl CoA is converted
into Succinate. Reaction
starts as inorganic phosphate
attaches to Succinyl CoA
displacing CoA. The
phosphate is picked up by
GDP forming GTP. The
terminal phosphate of GTP
is transferred to ADP
forming ATP
6 Succinate is oxidized to
Fumarate Reducing FAD to
FADH2
7 The addition of H20 to
Fumarate produces Malate
8 Oxaloacetate is reformed
through the oxidation of
Malate. NADH is formed
during the process
Summary of Transition Reaction and Kreb’s cycle
Each glucose that enters
Glycolysis is converted into
2 Pyruvate molecules
Transition Reaction
1 NADH/pyruvate
1 CO2 /pyruvate
Kreb’s Cycle
3 NADH/ Acetyl CoA
1FADH2 / Acetyl CoA
1ATP / Acetyl CoA
2CO2 / Acetyl CoA
Regulation of Transition Reaction
and Krebs Cycle
• The enzyme pyruvate dehydrogenase is regulated by
several molecules which either inhibit or activate its
activity.
• Ultimately, pyruvate dehydrogenase activity influences the
activity of the Krebs cycle
• Feedback inhibition also is used to regulate the Krebs cycle
Electron Transport Chain
Electron shuttling proteins
are called flavoproteins,
iron-sulphur proteins,
and cytochromes
Each protein in the series
is more electronegative
than its predecessor
• Each NADH enters the electron
transport chain with enough free
energy to fuel formation of 3 ATP
• Each FADH2 will yield 2 ATP
ETC
• Some electron carriers
of the transport chain
carry only electrons
– Ubiquinone
– Cytochrome c
• Some electron carriers
accept and release
protons along with
electrons
Chemiosmosis
Chemiosmosis: coupling of exergonic electron flow down an ETC to
endergonic ATP production by the creation of a proton gradient across a
membrane (proton-motive force)
ATP Formation
• ATP synthase couples
inorganic phosphate to
ADP as H+ return to
the matrix (utilizes
potential energy of
proton gradient)
• 1ATP is formed for
each H+ diffusing
across the membrane
Substrate-level Phosphorylation: ATP production coupled by direct enzymatic
transfer of phosphate from an intermediate in catabolism to ADP
Oxidative Phosphorylation: ATP production that is coupled to the exergonic
transfer of electrons from food to oxygen
Variations of Glycolysis
• In the absence of oxygen, liberation of energy can occur through
fermentation pathways yielding a max of 2 ATP/glucose
• Fermentation is similar to glycolysis except that the end product
is not pyruvate because of the addition of a few steps necessary
to regenerate NAD+
What about the other foods?
• Proteins, Carbo’s and Fats can
all be utilized for energy
following hydrolysis
• Amino Acids are converted to
intermediates including
pyruvate, acetyl CoA, and ketoglutarate
• Carbo’s enter glycolysis at the
beginning or as Fructose 6
phosphate
• Fats components
– glycerol enters as glyceraldehyde
phosphate
– Fatty acids enter as Acetyl CoA
Anabolic Synthesis
of Key Molecules
• Intermediates of
Carbohydrate
metabolism generate
the building blocks to
manufacture:
–
–
–
–
–
Amino acids
RNA
DNA
Phospholipids
Carbohydrate storage
products