Download Cellular Respiration

Cellular Respiration
• Life is work, which
requires E
• In most ecosystems,
E enters as sunlight
• Light E trapped in Omolecules is
available to both
photosynthetic
organisms and others
that eat them
• Cellular respiration and fermentation are
catabolic, energy-yielding pathways
• E is stored in molecules
• Enzymes catalyze the hydrolysis of high E
molecules to low E products
• Some of the released E is used to do
work; the rest is lost as heat
• Fermentation – leads to the partial
degradation of sugars in the absence of
O2
• Cellular respiration – A more efficient
and widespread catabolic process; uses
O2 as a reactant to complete the
breakdown of a variety of organic
molecules
–Carbohydrates, fats, and proteins can all
be used as the fuel
• ATP: pivotal molecule in cellular
energetics
• It is the chemical equivalent of a loaded
spring:
–The close packing of 3 negativelycharged phosphate groups is an
unstable, E-storing arrangement
–Loss of the end phosphate group
“relaxes” the “spring”
• Most cellular work converts ATP to ADP
and inorganic phosphate (Pi)
• Animal cells regenerate ATP from ADP
and Pi by the catabolism of organic
molecules
• The transfer of the last phosphate group from
ATP to another molecule is phosphorylation
–The receiving molecule changes shape,
performing work (transport, mechanical, or
chemical)
–When the
phosphate
groups leaves
the molecule,
the molecule
returns to its
original
shape
• Catabolic pathways relocate e-s stored in food
molecules, releasing E used to synthesize
ATP
• Redox rxns:
– Oxidation: loss of e-s
– Reduction: addition of e-s
• More generally: Xe- + Y  X + Ye– X, the e- donor, is the reducing agent which
is oxidized and reduces Y
– Y, the e- recipient, is the oxidizing agent
which is reduced and oxidizes X
• Redox reactions require both a donor and
acceptor
• O2: very potent oxidizing agent
• An electron loses E as it shifts from a less
electronegative atom to a more
electronegative one
• A redox rxn that relocates e-s closer to O2
releases chemical E that can do work
• To reverse the process, E must be added
to pull an e- away from an atom
• e-s “fall” from organic molecules to O2
during cellular respiration
–C6H12O6 + 6O2  6CO2 + 6H2O
• Glucose is oxidized, O2 is reduced, and
e-s lose potential E
• Molecules that have an abundance of
hydrogen are excellent fuels because their
bonds are a source of “hilltop” e-s that
“fall” closer to O2
• The cell has a rich reservoir of e-s
associated with hydrogen, especially in
carbohydrates and fats
• However, these fuels don’t spontaneously
combine with O2 because they lack the
activation E
• Enzymes lower the barrier of activation E,
allowing these fuels to be oxidized slowly
• The “fall” of e-s during respiration is
stepwise, via an ETC and NAD+
• Glucose and other fuels are broken down
gradually in a series of steps, each
catalyzed by a specific enzyme
• At key steps, H atoms are stripped from
glucose and passed first to a coenzyme,
like NAD+ (nicotinamide adenine
dinucleotide)
• Dehydrogenase enzymes strip two H
atoms from the fuel, pass two e-s and one
proton to NAD+ and release H+
• O2 and H2 could either combust and lose
all of the E as heat, or through a step-bystep process, the E could be harnessed to
form ATP
Mitochondrion
• Double membrane-bound organelle
–Outer membrane
–Intermembrane
space
–Inner
membrane
–Matrix
–Cristae: folds of inner membrane
Cellular
Respiration
• 3 phases:
–Glycolysis
–Krebs
cycle
–ETC
Substrate-level phosphorylation
• Enzymes transfer
phosphate from
O-molecule to
ADP
• Occurs in
glycolysis and
the Krebs cycle
Oxidative phosphorylation
• Occurs due to the ETC
• The transfer of e-s down the ETC to O2
powers the phosphorylation of ADP to ATP
• Produces almost 90% of the ATP
generated by respiration
Glycolysis
• Occurs in the cytoplasm
• Glucose (6-C sugar) is split ultimately into
two pyruvates
• Process occurs regardless of the
presence of O2
• No CO2 is produced
• Net E yield per glucose:
–2 ATP
–2 NADH
Glycolysis
• Each of the ten steps in glycolysis is
catalyzed by a specific enzyme
–Kinase: phosphorylates
–Isomerase: rearranges molecules to
form isomers
–Dehydrogenase: oxidizes O-molecules
• 10 steps can be divided into two phases:
–an E investment phase
–an E payoff phase
E investment phase
• ATP provides activation E by
phosphorylating glucose with 2 ATPs
E payoff phase
Krebs Cycle
• Pyruvate can now enter the mitochondrion
• The Krebs cycle can only accept a 2-C
molecule
• So, a multi-enzyme complex breaks down
the 3-C pyruvate to the 2-C acetate
• This process is known as pyruvic acid
breakdown
Pyruvic Acid Breakdown
• An enzyme rips off a carboxyl group in the
form of CO2 to make acetate
• In the process, NAD+ is reduced to NADH
• Coenzyme A then grabs the acetate,
making acetyl CoA, and carries it off to the
Krebs cycle
Pyruvic Acid Breakdown
Pyruvic Acid Breakdown
Krebs Cycle
• Occurs in the matrix of the mitochondrion
• The acetate from acetyl CoA bonds to
oxaloacetate to form citrate
• The cycle ultimately recycles
oxaloacetate, releasing CO2, ATP, NADH,
and FADH2 in the process
Krebs
Cycle
• Krebs cycle, per
glucose,
produces a total
of:
–8 NADH
–2 FADH2
–2 ATP
–6 CO2
• Krebs cycle, per
pyruvate,
produces half of
the above totals
ETC
• Only 4 of the 38 ATPs that are formed in
Cell Resp are formed by substrate-level
phosphorylation
• The other 34 come from the E from the e-s
carried by NADH and FADH2
• ETC is a chain of proteins found in the
inner membrane of the mitochondrion
–It’s folded (cristae) to increase surface
area
ETC
• Thousands of ETCs are found on the
cristae of a single mitochondrion
• NADH and FADH2 are oxidized as they
dump their e-s into the ETC
–FADH2 has less free E  it dumps its e-s
later in the ETC  fewer H+ move
across the membrane
ETC
ETC
• The e-s drop in free E as they are passed
along the ETC
• This loss of E drives H+ across the inner
membrane from the matrix to the intermembrane space (start of chemiosmosis)
• The high [H+] creates the proton-motive
force: ability of the proton gradient to do
work
ETC
• Each NADH contributes enough E to
generate a maximum of 3 ATP
• In some eukaryotic cells, NADH produced in
the cytosol by glycolysis may only be worth 2
ATP
– The e-s must be shuttled to the
mitochondrion
– In some shuttle systems, the e-s are
passed to NAD+, in others the e-s are
passed to FAD
• Each FADH2 can be used to generate about
2 ATP
ETC
ETC
• The high proton
concentration flows
through ATP
synthase from intermembrane space to
the matrix
• ATP synthase
makes ATP from
ADP and Pi
ETC
ETC
• Chemiosmosis is not unique to
mitochondria
–Plant cells use a very similar system in
the chloroplasts
–Prokaryotes generate H+ gradients
across their plasma membrane
Anaerobic Respiration
• Up to 38 ATPs can be generated when O2
is present
• What happens when there is no O2?
• Glucose can still be oxidized to make
ATP…much less ATP
Anaerobic Respiration
• Glycolysis still takes place in the cytosol,
which still produces:
–2 (net) ATP
–2 NADH
–2 pyruvate
• Pyruvate is harmful to cells and must be
broken down
Anaerobic Respiration
• The process is called fermentation
–Alcoholic fermentation
–Lactic acid fermentation
Alcoholic Fermentation
• The NADH made in glycolysis is used to
convert pyruvate into ethanol and CO2
• Glucose  pyruvate  acetaldehyde +
CO2  ethanol
Alcoholic Fermentation
• Utilized by yeast in the absence of O2
–CO2 produced by fermentation allows
bread to rise
–Ethanol utilized in production of beer
and wine
Alcoholic Fermentation
Lactic Acid Fermentation
• The NADH made in glycolysis is used to
convert pyruvate into lactate
• Glucose  pyruvate  lactate
Lactic Acid Fermentation
• Some fungi and bacteria are used to make
cheese, yogurt, sour cream, sauerkraut,
and pickles
• Muscle cells switch from aerobic to
anaerobic when O2 is depleted
–NADH and FADH2 cannot dump their e-s
into the ETC
–Krebs cycle stops making NADH and
FADH2, i.e., the cycle stops
–Pyruvate is not broken down
Lactic Acid Fermentation
• Lactate may cause muscle fatigue, but it is
ultimately converted back into pyruvate in
the liver
Aer- vs. Anaerobic Respiration
• Both perform glycolyis
• Both generate ATP
–Aerobic generates 38 ATP; both
substrate-level and oxidative
phosphorylation
–Anaerobic generates 2 ATP; only
substrate-level phosphorylation
• Both use NADH as e- carrier
Facultative Anaerobes
• Yeast and many bacteria (and humans at
the cellular level) can perform either type
Obligates
• Obligate aerobes: must live where O2 is
present
• Obligate anaerobes: must live where O2 is
not present
Fuels for E
• Glucose isn’t the only fuel used to make
ATP
• Other O-molecules can be broken down
and shoved into glycolysis, PAB, or the
Krebs cycle
• Other carbs, fats, and proteins can be
used
Other carbs for E
• Other monosaccharides can enter
glycolysis just like glucose
• Disaccharides are hydrolyzed into two
monosaccharides
• Polysaccharides are also hydrolyzed into
their monomer constituents
–Starch is digested into glucose in the
digestive system
–Glycogen is digested between meals
Fats for E
• Fats store 2X the E as carbs
• Broken into two parts: glycerol and the
fatty acids, which store most E
• Glycerol converts to G3P (PGAL)
• Fatty acids are broken down by beta
oxidation into 2-C fragments that enter
Krebs as acetyl-CoA
Proteins for E
• Digested into the individual amino acids
• aa’s must be daminated – amino group
removed
• The NH3 waste is removed as either
ammonia, urea, or other wastes
• The remaining portion can enter as
intermediates in either glycolysis, PAB, or
Krebs
Anabolic Pathways
• Not all the O-molecules of food are
completely oxidized to make ATP
• Intermediaries in glycolysis and Krebs can
be diverted to anabolic pathways
–Ex: a human cell can synthesize ~half
the 20 different aa’s by modifying
compounds from the Krebs cycle
Anabolic Pathways
–Glucose can be synthesized from
pyruvate and fatty acids from acetylCoA
–Excess carbs and proteins can be
converted to fats through intermediaries
of glycolysis and the Krebs cycle
Feedback Mechanisms
• Supply and demand regulate metabolic
economy
–If a cell has an excess of a certain
amino acid, it typically uses feedback
inhibition to prevent the diversion of
more intermediary molecules from the
Krebs cycle to the synthesis pathway of
that amino acid
Feedback Mechanisms
• The rate of catabolism is also regulated,
typically by the level of ATP in the cell
–If ATP levels drop, catabolism speeds up
to produce more ATP
–High levels of ATP inhibit the enzyme
phosphofructokinase (3rd step in glycol)
–It is stimulated by high levels of AMP
–Therefore, rate of glycolysis  as [ATP]
–And rate of glycolysis  as [ATP]
Feedback Mechanisms
• The rate of catabolism is also regulated by
citrate
• Citrate also inhibits phosphofructokinase
–As [citrate], glycolysis
–As [citrate], glycolysis
–This synchronizes the rate of glycolysis
and the Krebs cycle
Feedback Mechanisms
–Also, if intermediates from the Krebs
cycle are diverted to other uses (Ex:
amino acid synthesis), glycolysis speeds
up to replace these molecules