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Cellular Respiration
Lecture 8
Fall 2008
Overview of Cellular Respiration
• All organisms need ATP to do cellular work
• Cellular Respiration:
– The conversion of chemical energy of carbon
compounds into another form of chemical energy,
ATP
1
2
Overview of Cellular Respiration
Cellular respiration
• Metabolic pathway: Catabolic
– Series of multiple reactions
– Specific enzymes catalyze each reaction
• Function
– To generate ATP for cellular work
Three metabolic stages of cellular respiration
• Glycolysis
• The citric acid (Kreb’s) cycle
• Oxidative phosphorylation
Overview of Cellular Respiration
Each process occurs in
a specific area
• Glycolysis
– Cytosol of cell
• Citric acid cycle
– Matrix of mitochondria
• Oxidative
phosphorylation
– Inner membrane of
mitochondria
Fig. 9.6
3
4
Mitochondria
• Two membranes –outer & inner
• Intermembrane space –bound within the inner
and outer membranes
• Matrix – bound within the inner membrane
• Cristae – multiple infoldings of the inner
membrane
– Increases surface area
Fig. 6.17
5
Overview of Cellular Respiration
1. Gycolysis
• Glucose split into two molecules
of pyruvate
2. The citric acid cycle
• Acetate (derivative of pyruvate)
broken down into CO2
3. Oxidative phosphorylation:
electron transport &
chemiosmosis
• Electrons moved from NADH to
oxygen
• ATP produced
Fig. 9.6
6
Overview of Cellular Respiration
Purpose of Cellular Respiration
•To produce ATP
Fig. 9.6
– Some ATP generated at each step
– Most ATP generated during
electron transport (90%)
•Oxidative phosphorylation
– Production of ATP using energy
derived from the redox reactions of
an electron transport chain with
oxygen as its final electron
acceptor
•Substrate-level phosphorylation
– Production of ATP by an enzyme
directly transferring a phosphate
group from an intermediate
substrate to ADP
Fig. 9.7
Stage 1:Glycolysis
Glycolysis (“splitting of sugar”)
• Occurs in cytosol of cell
• One glucose (6-carbon sugar) converted to 2
pyruvate molecules (3-carbon sugar)
• Input
– One glucose molecule
– 2 ATP molecules
• Output
– 2 pyruvate molecules + 2 H2O
– 2 ATP molecules (net: 4 made, but 2 spent)
– 2 NADH (total of 4 electrons) + 2H+
• For electron transport chain
7
8
Stage 1:Glycolysis
Two phases
• Energy investment phase
• Energy payoff phase
Glycolysis: Energy Investment Phase
Energy investment phase
• 2 ATP molecules spent
• Enzymes needed for each step
• Hexokinase
– Phosphorylates glucose
– Charge prevents glucose from leaving cell
– Makes glucose more chemically reactive
• Phosphofructokinase
– Phosphorylates intermediary (Fructose-6phosphate)
– 6-carbon sugar with a phosphate group on
each end
• Aldolase
– Splits 6-carbon sugar to 2 3-carbon sugars
(one of which is glyceraldehyde-3-phosphate)
Fig. 9.9
9
Glycolysis: Energy Investment Phase
10
Regulation : Phosphofructokinase
• Inhibited by high concentrations
of ATP
• Stimulated by high
concentrations of ADP (AMP:
adenosine monophosphate)
• Allosteric
Fig. 9.21
Glycolysis: Energy Payoff Phase
• Triose phosphate dehydrogenase
– Oxidizes glyceraldehyde-3-phosphate
• 2 electrons transferred to NAD+ (now
NADH)
– Exergonic reaction
• Energy from redox reaction used to
phosphorylate glyceraldehyde-3-phosphate
• Phosphoglycerokinase
– Transfers phosphate from intermediary
(1,3 Bisphosphoglycerate) to ADP
– Substrate-level phosphorylation
•
Intermediary is now an organic acid
(no longer a sugar)
Fig. 9.9
11
Glycolysis: Energy Payoff Phase
• Enolase
– Increases the potential energy of
the intermediary by removing water,
causing double bond to form
(phosphoenolpyruvate -PEP)
• Pyruvate kinase
– Transfers phosphate group from
PEP to ATP
• Pyruvate is end product
Fig. 9.9
12
Stage 2: The Citric Acid Cycle
“Pre” citric acid cycle
• Pyruvate transported into mitochondria
• Carboxl group removed
• 2-carbon compound oxidized to acetate
– NAD+ reduced
• Acetate bound to Coenzyme A = Acetyl CoA
– Coenzyme A: carrier molecule that makes acetic acid more
reactive (high potential energy)
Fig. 9.10
13
14
Stage 2: The Citric Acid Cycle
Regulation: Pyruvate dehydrogenase
• Enzyme complex where pyruvate transformed to
acetyl CoA
• Requires vitamin B-complex as coenzymes
• Inhibited by high concentration of ATP
– Becomes phosphorylated/inactive
• Stimulated by ADP (AMP)
• Allosteric
Fig. 9.10
15
Stage 2: The Citric Acid Cycle
Citric Acid (Kreb’s) Cycle
• Occurs in matrix of mitochondria
• Acetyl CoA broken down into
CO2
• Input (for every one glucose molecule)
– 2 acetyl CoA molecules
• Output
– 6 CO2 (includes CO2 released
during “pre” stage)
– 2 ATP
• (GTP – guanosine triphosphate)
– 6 NADH & 2 FADH2
• To electron transport chain
Fig. 9.11
Stage 2: The Citric Acid Cycle
16
• Acetyl CoA attached to
oxaloacetate to form citrate
• Oxaloacetate regenerated
by intermediaries in cycle
• ATP (GTP) produced by
substrate level
phosphorylation
• Redox reactions
– NAD+ reduced to NADH
– FAD reduced to FADH2
Fig. 9.12
Stage 2: The Citric Acid Cycle
17
Regulation
• Enzyme that converts acetyl
CoA to citrate inhibited by
ATP
– Allosteric
• Enzyme that converts
isocitrate to a-ketogluterate
inhibited by NADH
– Competitive
Fig. 9.12
18
Stage 3: The ETC & Chemiosmosis
Majority of ATP produced in this stage
Electron Transport Chain
• Many protein complexes & nonprotein components embedded in
the inner membrane of the
mitochondria
– High surface area (cristae), so many
ETCs
• Electrons provide by NADH & FADH2
– FADH2 adds electrons further down ETC
– provides less energy
• Electrons ”fall” down chain: Redox
reactions
– H2O formed
• Produces energy at each step
Fig. 9.13
19
Stage 3: The ETC & Chemiosmosis
• Transfer of electrons activates pumping of H+
• H+ pumped from matrix, across the inner membrane,
and into the intermembrane space of the mitochondria
• Creates a concentration gradient (driving force) of H+
across the inner membrane
Fig. 9.16
Stage 3: The ETC & Chemiosmosis
Chemiosmosis
• Concentration gradient of H+
harnessed to do work
• Through ATP synthase
– Enzymes generate ATP from
ADP + P = phosphorylation
– Oxidative phosphorylation
Fig. 9.14
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21
ATP Production
~ 38 ATP created per one glucose molecule
• Glucose = 686 kcal/mol
• ATP = 7.3 kcal/mol
• 40% efficiency
Fig. 9.17
22
Versatility of Cellular Respiration
• Glucose is not the
only molecule used in
cellular respiration
Fig. 9.20
23
Anabolic Pathways
• Cellular respiration supplies precursor molecules
for anabolic pathways
Metabolic Diversity
What about organisms that live in areas with no oxygen?
– Anaerobic - lacking oxygen
• They need to produce ATP, but do not have oxygen to
act as an electron acceptor
• Use anaerobic respiration or fermentation
• Anaerobic respiration
– Uses a different final electron acceptor (not oxygen) in ETC
• E.g., sulfate ion
• Fermentation
– A process that makes a limited amount of ATP from glucose
without using an ETC or oxygen
– Utilizes glycolysis
– Requires recycling of NADH to NAD+ (typically done in ETC)
24
25
Metabolic Diversity
• Alcohol fermentation
– Regeneration of NAD+ produces
ethanol
– Releases CO2
• Yeast: bread, beer
• Lactic acid fermentation
– Regeneration of NAD+ produces
lactate
– No release of CO2
• Cheese, yogurt
Use of fermentation in humans?
• Less efficient than cellular
respiration
– 2 ATP vs. ~38 ATP
Fig. 9.18
Metabolic Diversity
Obligate aerobes
• Require O2 for cellular respiration
Facultative anaerobes
• Use O2 in cellular respiration if present
• Use fermentation in an anaerobic environment
Obligate anaerobes
• Must live in anaerobic environment
– poisoned by O2
• Use fermentation or anaerobic respiration
26
Evolution of PS & CR
• Oldest prokaryote
~3.5 bya
• No oxygen in
atmosphere until
~2.7 bya
• Glycolysis
– Occurs in matrix
– Does not require
ETC or O2
– Enzymes from
glycolysis observed
in almost all
bacteria, archaea &
eukaryotes studied
Fig. 26.10
27
Evolution of PS & CR
• Evolution of electron transport systems > 3 bya
– Evolution of photosystems
– Evolution of anaerobic respiration
• Development of atmospheric oxygen > 2.7 bya
– Cyanobacteria
– Evolution of aerobic respiration
• Evolution of eukaryotes~ 2.1 bya
28
Endosymbiosis
Endosymbiosis
• One organism of a certain species lives inside
another organism of a different species
• Process where unicellular organisms engulf
other unicellular organisms
Endosymbiosis theory
• The theory that mitochondria and chloroplasts
evolved from prokaryotes that were engulfed by
host cells and took up a symbiotic existence
within those cells.
• Over time, evolved into organelle of the cell
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Endosymbiosis
Mitochondria
• Formed when early anaerobic
eukaryotic cell engulfed an
aerobic bacterium
• Benefits?
Plastids
• Formed when early eukaryotic
cell engulfed a photosynthetic
cyanobacterium
• Benefits?
Mitochondria evolved before
plastids
– All eukaryotes have
mitochondria or remnants of
mitochondria
– Not all eukaryotes have
plastids
Endosymbiosis
Evidence
Mitochondria & chloroplasts:
• Similar size to bacteria
• Have own ribosomes, similar to bacterial
ribosomes
• Inner membranes have enzymes and transport
systems homologous to living prokaryotes
• Reproduction - binary fission
• Circular DNA with few or no proteins
• Mitochondrial DNA sequencing and ribosomal
RNA sequencing from chloroplasts support the
structural and molecular evidence
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