An overview of cellular respiration

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An overview of cellular respiration
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• Basic Concept The citric acid cycle completes
  the energy-yielding oxidation of organic
  molecules
• The citric acid cycle
• Eight enzyme catalyzed steps
• Occurs in the matrix of the mitochondrion

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• Before the citric acid cycle can begin
• Pyruvate must first be converted to acetyl CoA,
  which links the cycle to glycolysis

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• An overview of the citric acid cycle

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Citric Acid Cycle Bottom Line

• The conversion of each acetyl CoA in the citric
  acid cycle results in
• One ATP produced by substrate-level
  phosphorylation
• Three NAD reduced to NADH
• One FAD reduced to FADH2
• Two CO2 molecules

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Figure 9.12
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The Electron Transport Chain

• Basic Concept Electron transport extracts energy
  from high energy electrons to synthesize ATP
• NADH and FADH2
• Donate electrons to the electron transport chain
  (ETC), which lose energy in several steps

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Electron TransportChain
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ETC

• Each successive carrier has a greater
  electronegativity than the previous one
• At the end of the chain electrons are passed to
  oxygen, forming water

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• Chemiosmosis
• Is an energy-coupling mechanism that uses energy
  in the form of a H gradient across a membrane to
  drive cellular work

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Chemiosmosis

• Peter Mitchell (1961) hypothesized that
• At certain steps along the electron transport
  chain
• Electron transfer causes proteins to pump H from
  the mitochondrial matrix to the intermembrane
  space
• This produces a proton gradient (i.e.,
  electrochemical gradient).

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• The resulting H gradient across the IMM
• Stores energy
• Drives chemiosmosis in ATP synthase
• Is referred to as a proton-motive force

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E. M. of Mitochondrial Inner Membrane Proteins
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ATP Synthase Molecules
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ATP Synthase Molecule
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Chemiosmosis and the electron transport chain
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Experimental Evidence for Chemiosmosis

• Measured pH of mitochondrial matrix relative to
  IMS (space) in metabolically active mitochondria
• Predict relative pH of IMS (space) _______

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Experimental Evidence for Chemiosmosis

• Isolated mitochondria and incubated in vitro with
  O2, ADP, PO4 but no e- donors (no NADH or FADH2),
  thus, no electron transport.
• Exp a Added NADH to incubation.
• Predict what would happen to pH of IM space.
• Exp. b Added excess H (acid) to incubation.
• Predict what would happen to ATP syn.

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Experimental Evidence for Chemiosmosis

• 2,4-dinitrophenol (DNP)
• Lipid-soluble makes inner membrane permeable to
  protons
• Binds protons carries them across membrane into
  matrix
• Abolishes proton gradient across IMM
• In 1940s used as diet pill (until patients died)
• Explain why DNP caused weight loss

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Experimental Evidence for Chemiosmosis

• In 1997, found mitochondrial protein acting as
  natural (endogenous) uncoupling protein (UCP)
• Makes IMM permeable to protons
• Uncoupling protein found in inner mitochondrial
  membrane of different cells (e.g., adipocytes,
  muscle)
• Abolishes proton gradient across IMM
• May help determine basal metabolic rate may be
  clue to physiological basis of obesity

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Chemiosmosis The Energy-Coupling Mechanism

• ATP synthase is the enzyme that actually makes ATP

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An Accounting of ATP Production by Cellular
Respiration

• During respiration, most energy flows in the
  following sequence
• Glucose ? NADH ? electron transport chain ?
  proton-motive force ? ATP

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• There are three main processes in this metabolic
  enterprise

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• Each NADH from the citric acid cycle and
  glycolysis contributes enough energy to generate
  approximately 3 ATP (rounding up).
• Each FADH2 from the citric acid cycle can be used
  to generate about 2 ATP.
• This plus the 4 ATP from substrate-level
  phosphorylation gives a bottom line of 36 - 38
  ATP.

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How efficient is respiration in generating ATP?

• Complete oxidation of glucose releases 686 kcal
  per mole.
• Formation of each ATP requires at least 7.3
  kcal/mole.
• Efficiency of respiration is 7.3 kcal/mole x 38
  ATP/glucose/686 kcal/mole glucose ? 40 of the
  energy in a glucose molecule is captured in ATP
• The other approximately 60 is lost as heat.

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The Evolutionary Significance of Glycolysis

• Glycolysis
• Can produce ATP with or without oxygen, in
  aerobic or anaerobic conditions
• Occurs in nearly all organisms
• Probably evolved in ancient prokaryotes before
  there was oxygen in the atmosphere