CELLULAR RESPIRATION

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Metabolism
- intersecting set
of chemical
pathways
- choreographed
interplay of
different
molecules
 Catabolism and ATP production
organic compounds + oxygen 

carbon dioxide + water + energy

 Oxidation and Reduction Reactions
- transfer of electrons during chemical reactions
is the basis for the energy yield during
catabolism
- OXIDATION: the loss of electrons (e-) from one
substance
- REDUCTION: addition of e- to another substance
(reduction of the amount of positive charge)
Oxidation and Reduction Reactions
Oxidation and Reduction Reactions
 Oxidation and Reduction Reactions
- not all redox reactions involve complete transfer
of electrons from one substance to another
- some redox change the degree of electron
sharing in covalent bonds
- when methane reacts with oxygen, electrons end
up closer to oxygen (which is very
electronegative)
- carbon partially “lost” its electrons and is
oxidized (see preceding diagram)
- oxygen has partially “gained” electrons and is
thus reduced (see preceding diagram)
Oxidation and Reduction Reactions
- energy must be added to pull an electron away
from an atom
- the more electronegative the atom, the more
energy is required to take electrons from it
- an electron loses potential energy when it
shifts from a less electronegative atom toward
a more electronegative one
- redox reactions that relocates electrons closer
to oxygen release chemical energy thatcan be
put to work
 Oxidation of organic fuel

- organic molecules rich in hydrogen are excellent

fuels
- their bonds are a source of electrons whose
energy must be released as the electrons are
transferred to oxygen
 Oxidation of organic fuel
- carbohydrates and fats
are reservoir of electrons
- body temperature not
enough to initiate
burning of these fuels
- enzymes will lower
activation energy barrier
 allow stepwise
oxidation of fuel
 Stepwise energy harvest
- energy from fuel is not released all at once so
that it can be harnessed efficiently
- oxidation of glucose is not done in a single
explosive step
- oxidation of organic fuel in a series of steps,
each step catalyzed by an enzyme
- occurs via NAD+ and electron transport chain
 Stepwise energy harvest
- each electron travels with
a proton (as a hydrogen
atom)
- H atoms are not directly
transferred to oxygen
- H atoms are passed first to
NAD+ (nicotinamide
adenine dinucleotide, a
coenzyme derived from
niacin)
 Stepwise energy harvest
- enzymes (DEHYDROGENASES) remove a pair
of hydrogen atoms (2 e- and 2 H+) from a
substrate (e.g. glucose); the substrate is
oxidized
- dehydrogenases deliver 2 e- and one H+ to
NAD+; the other H+ is released into
surrounding solution
 Stepwise energy harvest

- NAD+ receives 2 e- and one H+

- NAD+ is reduced to NADH
 Stepwise energy harvest
- electrons lose very little of their potential
energy when transferred to NAD+
- NADH represents stored energy that can be
tapped to make ATP when electrons are
transferred to oxygen
 Stepwise energy transfer
- electron transport chain break the fall of
electrons to oxygen into several energy-
releasing steps instead of one explosive reaction
- transport chain consists of a number of
molecules (mostly proteins) built into inner
mitochondrial membrane
- electrons are shuttled by NADH to “top” higher
energy end of the chain
- at the “bottom” lower energy end, oxygen
captures electrons along with H+, forming water
Stepwise energy transfer
 Stepwise energy transfer
- electron transfer from NADH to oxygen is an
exergonic reaction
- energy released is not wasted in a single
explosive step; rather electrons cascade down
the chain from one carrier molecule to
another to the next, losing a small amount of
energy with each step until finally reaching
oxygen
Stages of cellular respiration
OXIDATIVE PHOSPHORYLATION
- ATP synthesis using the energy released at
each step of electron transport chain
- accounts for 90% of ATP generated during
cellular respiration
SUBSTRATE-LEVEL PHOSPHORYLATION
- phosphate group is transferred to ADP from a
substrate molecule, forming ATP
 Glycolysis
- occurs in the cytosol
- “splitting of sugar”
- Glucose (a hexose: 6-C sugar) is split into two
3-C sugars
- the two 3-C sugars are oxidized; remaining
atoms rearranged to form two pyruvate
molecules
- 10-step pathway divided into 2 phases
 Glycolysis
ENERGY INVESTMENT PHASE
- here, the cell spends ATP
- investment is repaid later

ENERGY PAYOFF PHASE

- ATP is produced (by substrate level
phosphorylation)
- NAD+ is reduced to NADH by electrons released
from oxidation of food (e.g. glucose)
 Glycolysis
- yields a net of 2 ATP molecules per one
glucose molecule
- also yields 2 NADH
- occurs in the presence or absence of oxygen
- releases less than ¼ of the stored chemical
energy in glucose
- more energy is stockpiled in pyruvate
Glycolysis
 Junction between glycolysis and
citric acid cycle
- if molecular oxygen is present, pyruvate enters
mitochondrion via active transport
- pyruvate is then converted to acetyl coenzyme
A (acetyl CoA)
 Junction between glycolysis and
citric acid cycle
CONVERSION OF PYRUVATE TO ACETYL COA
- carboxyl group (-COO-) of pyruvate is
removed and released as CO2
- acetate (2-C) is further oxidized; electrons
extracted are transferred to NAD+ (which
stores energy in the form of NADH)
- acetyl group (attached acetate) of acetyl CoA
is fed to TCA cycle
 Citric acid cycle
- occurs in the mitochondrion (specifically
inside the mitochondrial matrix)
- completes the oxidation of the organic fuel
- AKA tricarboxylic acid cycle (TCA) or Krebs
cycle
- functions as a metabolic furnace that oxidizes
organic fuel derived from pyruvate
 Citric acid cycle
- breaks down pyruvate to 3 CO2 molecules
- generates 1 ATP per turn by substrate-level
phosphorylation
- most of the energy is transferred to NAD+ and
FAD (now in the reduced forms NADH and
FADH2 ,which shuttle the electrons to the
electron transport chain)
- an 8-step pathway, each step catalyzed by a
specific enzyme
Citric acid cycle
Citric
acid
cycle
 Oxidative phosphorylation
- NADH and FADH2 carry the electrons extracted
from fuel (e.g. glucose) via glycolysis and TCA
cycle to the electron transport chain (ETC)
- ETC is the machinery of oxidative
phosphorylation
- energy released by ETC is used to power ATP
synthesis
- Inner mitochondrial membrane couples electron
flow down the chain to ATP synthesis
 Oxidative phosphorylation
ELECTRON TRANSPORT CHAIN
- collection of molecules embedded in the inner
mitochondrial membrane
- folded cristae increases surface area, providing
thousands of copies of the chain in each
mitochondrion
- components are mostly proteins, existing in
multiprotein complexes (I-IV)
 Oxidative phosphorylation
- as electrons are transported along the chain,
electron carriers alternate between reduced
and oxidized states as they accept and donate
electrons
- the “uphill” electron carrier is less
electronegative than its neighboring
“downhill” electron carrier, thus passing the
electrons to it
Oxidative phosphorylation
 Oxidative phosphorylation
ELECTRON TRANSPORT CHAIN
* complex I – a flavoprotein; contains flavin
mononucleotide (FMN)
* complex II – an iron-sulfur protein
* ubiquinone (Q) – a small hydrophobic
molecule; the only non-protein member of ETC
* cytochromes – proteins with heme group
containing iron atom that accepts and donates
electrons
 Oxidative phosphorylation
ELECTRON TRANSPORT CHAIN
- does not make ATP directly
- eases the fall of electrons from food to
oxygen
 Oxidative phosphorylation
ATP SYNTHASE
- protein complex in the inner mitochondrial
membrane
- enzyme that makes ATP from ADP and inorganic
phosphate
- works like an ion pump acting in reverse
- uses energy of an existing ion gradient (H+
gradient or PROTON-MOTIVE FORCE) to power
ATP synthesis
 Oxidative phosphorylation
CHEMIOSMOSIS
- process in which
energy stored in
the form of H+
gradient across a
membrane is used
to drive cellular
work (e.g. ATP
synthesis)
Oxidative phosphorylation
 Oxidative phosphorylation
ELECTRON TRANSPORT CHAIN
- creates the H+ gradient that drives ATP synthesis
- an energy converter uses the exergonic flow of
electrons to pump H+ across the membrane
- H+ diffuses back across the membrane only through the
channel in the ATP synthase
- ATP uses exergonic flow of H+ to drive phosphorylation
of ADP
ENERGY STORED IN AN H+ GRADIENT ACROSS
MEMBRANE COUPLES REDOX REACTIONS OF
ETC TO ATP SYNTHESIS.
 How does ETC pump electrons?
- Some ETC members accept and release H+ along
with electrons
- at certain steps along the chain, electron
transfers cause H+ to be taken up and released in
surrounding solution
ATP accounting
 ATP production without oxygen

FERMENTATION
- mechanism by which cells can oxidize organic
fuel and generate ATP WITHOUT USING
OXYGEN (ANAEROBIC)
- consists of glycolysis plus reactions that
regenerate NAD + by transferring electrons
from NADH to pyruvate or its derivatives
 ATP production without oxygen
LACTIC ACID FERMENTATION
 ATP production without oxygen
ALCOHOL FERMENTATION
Interconnection of
metabolic
pathways
 Biosynthesis (Anabolism)
- Not all organic molecles of food are oxidized
as fuel to make ATP
- Food also provide carbon skeletons to make
other molecules
e.g. some metabolic intermediates from citric
acid cycle can be modified to make some
amino acids
pyruvate can be made into glucose
acetyl CoA can be used to synthesize fatty
acids
 Regulation of cellular respiration
- Supply and demand regulate metabolic
economy
- The cell does not waste energy making more
of a substance than it needs

FEEDBACK INHIBITION
- end product of a pathway inhibits the
enzyme that catalyzes an earlier step in
thepathway
 Important concepts
• Catabolic pathways yield energy by OXIDIZING
organic fuels
• Glycolysis harvests chemical energy by oxidizing
glucose to pyruvate
• The citric acid cycle completes the energy-yielding
oxidation of organic molecules
• During oxidative phosphorylation, chemiosmosis
couples electron transport to ATP synthesis
• Fermentation enables some cells to produce ATP
without using oxygen
• Glycolysis and the citric acid cycle connect to many
other metabolic pathways