Cellular Respiration

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Cellular Respiration
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• Life is work, which requires E
• In most ecosystems, E enters as sunlight
• Light E trapped in O-molecules is available to
  both photosynthetic organisms and others that eat
  them

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• 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

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• 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

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• ATP pivotal molecule in cellular energetics
• It is the chemical equivalent of a loaded spring
• The close packing of 3 negatively-charged
  phosphate groups is an unstable, E-storing
  arrangement
• Loss of the end phosphate group relaxes the
  spring

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• 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

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• 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

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• 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

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• 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

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• 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

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• The cell has a rich reservoir of e-s associated
  with hydrogen, especially in carbohydrates and
  fats
• However, these fuels dont 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

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• 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

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• O2 and H2 could either combust and lose all of
  the E as heat, or through a step-by-step process,
  the E could be harnessed to form ATP

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Mitochondrion

• Double membrane-bound organelle
• Outer membrane
• Inter- membrane space
• Inner membrane
• Matrix
• Cristae folds of inner membrane

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Cellular Respira-tion

• 3 phases
• Glyco- lysis
• Krebs cycle
• ETC

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Substrate-level phosphorylation

• Enzymes transfer phosphate from O-molecule to ADP
• Occurs in glycolysis and the Krebs cycle

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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

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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

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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

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E investment phase

• ATP provides activation E by phosphorylating
  glucose with 2 ATPs

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E payoff phase
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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

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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

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Pyruvic Acid Breakdown
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Pyruvic Acid Breakdown
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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

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Krebs Cycle
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• 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

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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
• Its folded (cristae) to increase surface area

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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

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ETC
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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 inter-membrane
  space (start of chemiosmosis)
• The high H creates the proton-motive force
  ability of the proton gradient to do work

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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

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ETC
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ETC

• The high proton concentration flows through ATP
  synthase from inter-membrane space to the matrix
• ATP synthase makes ATP from ADP and Pi

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ETC
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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

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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 ATPmuch
  less ATP

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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

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Anaerobic Respiration

• The process is called fermentation
• Alcoholic fermentation
• Lactic acid fermentation

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Alcoholic Fermentation

• The NADH made in glycolysis is used to convert
  pyruvate into ethanol and CO2
• Glucose ? pyruvate ? acetaldehyde CO2 ? ethanol

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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

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• Alcoholic Fermentation

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Lactic Acid Fermentation

• The NADH made in glycolysis is used to convert
  pyruvate into lactate
• Glucose ? pyruvate ? lactate

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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

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Lactic Acid Fermentation

• Lactate may cause muscle fatigue, but it is
  ultimately converted back into pyruvate in the
  liver

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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

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Facultative Anaerobes

• Yeast and many bacteria (and humans at the
  cellular level) can perform either type

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Obligates

• Obligate aerobes must live where O2 is present
• Obligate anaerobes must live where O2 is not
  present

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Fuels for E

• Glucose isnt 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

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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

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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

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Proteins for E

• Digested into the individual amino acids
• aas 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

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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 aas by modifying compounds from the
  Krebs cycle

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Anabolic Pathways

• Glucose can be synthesized from pyruvate and
  fatty acids from acetyl-CoA
• Excess carbs and proteins can be converted to
  fats through intermediaries of glycolysis and the
  Krebs cycle

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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

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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?

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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

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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