How cells Make ATP: Energy Releasing Pathways

1

• How cells Make ATP Energy Releasing Pathways

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Metabolism

• Metabolism has two complementary components
• catabolism, which releases energy by splitting
  complex molecules into smaller components
• anabolism, the synthesis of complex molecules
  from simpler building blocks
• Most anabolic reactions are endergonic and
  require ATP or some other energy source to drive
  them

3
Cellular Respiration

• Every organism extracts energy from food
  molecules that it manufactures by photosynthesis
  or obtains from the environment
• Exergonic metabolic pathways (cellular
  respiration and fermentation) release free energy
  that is captured by the cell
• cellular respiration
• Catabolic processes that convert energy in the
  chemical bonds of nutrients to chemical energy
  stored in ATP
• May be either aerobic or anaerobic

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Aerobic Respiration

• Cells use aerobic respiration to obtain energy
  from glucose
• C6H12O6 6 O2 6 H2O ?
• 6 CO2 12 H2O energy (chemical bonds of ATP)
• aerobic respiration
• Cellular respiration that requires molecular
  oxygen (O2)
• Nutrients are catabolized to carbon dioxide and
  water

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Aerobic Respiration (cont.)

• Aerobic respiration is a redox reaction in which
  glucose becomes oxidized and oxygen becomes
  reduced
• Aerobic respiration transfers electrons
  (associated with hydrogen atoms in glucose) to
  oxygen in a series of steps that control the
  amount of energy released
• Free energy of the electrons is coupled to ATP
  synthesis
• Aerobic respiration is an exergonic redox process
  in which glucose becomes oxidized, oxygen becomes
  reduced, and energy is captured to make ATP

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The Four Stages of Aerobic Respiration
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Summary of Aerobic Respiration
Table 8-1, p. 174
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Reactions Involved in Aerobic Respiration

• dehydrogenations
• Reactions in which two hydrogen atoms are removed
  from the substrate and transferred to NAD or FAD
• decarboxylations
• Reactions in which part of a carboxyl group
  (COOH) is removed from the substrate as a
  molecule of CO2
• Other reactions
• Reactions in which molecules are rearranged so
  they can undergo further dehydrogenations or
  decarboxylations

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Introduction to Glycolysis

• Glycolysis
• Takes place in the cytosol
• Metabolizes the 6-carbon sugar glucose into two
  3-carbon molecules of pyruvate
• Does not require oxygen proceeds under aerobic
  or anaerobic conditions
• Net yield 2 ATP molecules and 2 NADH molecules
• Two major phases
• Endergonic reactions that require ATP (investment
  phase)
• Exergonic reactions that yield ATP and NADH
  (payoff phase)

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GLYCOLYSIS
Glucose
Energy investment phase and splitting of glucose
Two ATPs invested per glucose
3 steps
Fructose-1,6-bisphosphate
Glyceraldehyde phosphate (G3P)
Glyceraldehyde phosphate (G3P)
Energy capture phase Four ATPs and two NADH
produced per glucose
(G3P)
(G3P)
5 steps
Pyruvate
Pyruvate
Net yield per glucose Two ATPs and two NADH
Fig. 8-3, p. 176
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First Phase of Glycolysis

• Phosphate groups are transferred from ATP to
  glucose In two separate phosphorylation reactions
• The phosphorylated sugar (fructose-1,6-bisphosphat
  e) is broken enzymatically into two three-carbon
  molecules, yielding 2 glyceraldehyde-3-phosphate
  (G3P)
• glucose 2 ATP ? 2 G3P 2 ADP

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Second Phase of Glycolysis

• G3P is converted to pyruvate
• G3P is oxidized by removal of 2 electrons (as
  hydrogen atoms), which combine with NAD
• NAD 2 H ? NADH H
• ATP is formed by substrate-level phosphorylation
• 2 G3P 2 NAD 4 ADP ? 2 pyruvate 2 NADH 4
  ATP

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Energy investment phase and splitting of glucose
Two ATPs invested per glucose
Glucose
Hexokinase
1
Glucose-6-phosphate
Phosphoglucoisomerase
Fig. 8-4a (1), p. 178
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2
Fructose-6-phosphate
Phosphofructokinase
3
Fructose-1,6-bisphosphate
Aldolase
4
Isomerase
5
Glyceraldehyde- 3-phosphate (G3P)
Dihydroxyacetone phosphate
Fig. 8-4a (2), p. 178
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Two glyceraldehyde-3-phosphate (G3P) from bottom
of previous page
Energy capture phase Four ATPs and two NADH
produced per glucose
Glyceraldehyde-3-phosphate dehydrogenase
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Two 1,3-bisphosphoglycerate
Phosphoglycerokinase
7
Two 3-phosphoglycerate
Phosphoglyceromutase
Fig. 8-4b (1), p. 179
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8
Two 2-phosphoglycerate
Enolase
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Two phosphoenolpyruvate
Pyruvate kinase
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Two pyruvate
Fig. 8-4b (2), p. 179
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Pyruvate is Converted to Acetyl CoA

• Pyruvate undergoes oxidative decarboxylation
• A carboxyl group is removed as CO2, which
  diffuses out of the cell
• Occurs in mitochondria of eukaryotes
• The two-carbon fragment is oxidized (NAD accepts
  the electrons), and is attached to coenzyme A,
  yielding acetyl coenzyme A (acetyl CoA)
• 2 pyruvate 2 NAD 2 CoA ?
• 2 acetyl CoA 2 NADH 2 CO2

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Formation of Acetyl CoA
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Overview of the Citric Acid Cycle

• The citric acid cycle is also known as the Krebs
  cycle
• Takes place in the matrix of the mitochondria
• A specific enzyme catalyzes each of the eight
  steps
• Begins when acetyl CoA transfers its two-carbon
  acetyl group to the four-carbon acceptor compound
  oxaloacetate, forming citrate, a six-carbon
  compound
• oxaloacetate acetyl CoA ? citrate CoA

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The Citric Acid Cycle (cont.)

• Citrate goes through a series of chemical
  transformations, losing two carboxyl group as CO2
• One ATP is formed (per acetyl group) by
  substrate-level phosphorylation most of the
  oxidative energy (in electrons) is transferred to
  NAD, forming 3 NADH
• Electrons are also transferred to FAD, forming
  FADH2

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Overview of the Citric Acid Cycle
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Introduction to the Electron Transport Chain

• All electrons removed from a glucose during
  glycolysis, acetyl CoA formation, and the citric
  acid cycle are transferred as part of hydrogen
  atoms to NADH and FADH2
• NADH and FADH2 enter the electron transport chain
  (ETC), where electrons move from one acceptor to
  another
• Some electron energy is used to drive synthesis
  of ATP by oxidative phosphorylation

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Transfer of Electrons

• In eukaryotes, the ETC is a series of electron
  carriers embedded in the inner mitochondrial
  membrane
• Electrons pass down the ETC in a series of redox
  reactions, losing some of their energy at each
  step along the chain

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Transfer of Electrons (cont.)

• Cytochrome c reduces O2, forming H2O
• Oxygen is the final electron acceptor in the ETC
• Lack of oxygen blocks the entire ETC no
  additional ATP is produced by oxidative
  phosphorylation
• Some poisons also inhibit normal activity of
  cytochromes
• Example Cyanide binds to iron in cytochrome,
  blocking ATP production

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Overview of the Electron Transport Chain
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The Chemiosmotic Modelof ATP Synthesis

• 1961 Peter Mitchell proposed that electron
  transport and ATP synthesis are coupled by a
  proton gradient across the inner mitochondrial
  membrane in eukaryotes (chemiosmosis)
• Mitchells experiments used a bacterial model
• Bacterial cells placed in an environment with a
  high hydrogen ion (proton) concentration
  synthesized ATP even if electron transport was
  not taking place

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KEY EXPERIMENTEvidence for Chemiosmosis
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Bacterial cytoplasm (low acid)
Synthesized
Plasma membrane
Acidic environment
Fig. 8-9, p. 183
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The Proton Gradient

• As electrons pass down the ETC, energy is used to
  move protons (H) across the inner mitochondrial
  membrane into the intermembrane space
• The intermembrane space has a higher
  concentration of protons the mitochondrial
  matrix has a lower concentration
• The resulting proton gradient is a form of
  potential energy that provides energy for ATP
  synthesis

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The Proton Gradient
Outer mitochondrial membrane
Cytosol
Inner mitochondrial membrane
Intermembrane spacelow pH
Matrixhigher pH
Fig. 8-10, p. 184
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Synthesis of ATP

• Protons diffuse from the intermembrane space
  (high concentration) to the matrix (low
  concentration) through the enzyme complex ATP
  synthase
• A central structure of ATP synthase rotates,
  catalyzing the phosphorylation of ADP to form ATP
  
• Chemiosmosis allows exergonic redox reactions to
  drive the endergonic reaction in which ATP is
  produced by oxidative phosphorylation

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Overview of the ETC
Cytosol
Outer mitochondrial membrane
Intermembrane space
Complex V ATP synthase
Complex III
Complex IV
Inner mitochondrial membrane
Complex I
Complex II
Matrix of mitochondrion
Fig. 8-11a, p. 185
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ATP Production

• Aerobic respiration of one glucose molecule
• Glycolysis glucose 2 ATP ? 2 pyruvates 2
  NADH 4 ATPs (net profit of 2 ATPs)
• Pyruvate conversion 2 pyruvates ? 2 acetyl CoA
  2 CO2 2 NADH
• Citric acid cycle 2 acetyl CoA ? 4 CO2 6 NADH
  2 FADH2 2 ATPs
• Total 4 ATP 10 NADH 2 FADH2

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ATP Production (cont.)

• Oxidation of NADH in the electron transport chain
  yields up to 3 ATPs per molecule (10 NADH X 3
  30 ATPs)
• Oxidation of FADH2 yields 2 ATPs per molecule
• (2 FADH2 X 2 4 ATPs)

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ATP Production (cont.)

• Summing all the ATPs
• 2 from glycolysis
• 2 from the citric acid cycle
• 32 to 34 from electron transport and chemiosmosis
• Complete aerobic metabolism of one molecule of
  glucose yields a maximum of 36 to 38 ATPs

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Energy Yield from Oxidation of Glucose by Aerobic
Respiration
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Cells Regulate Aerobic Respiration

• Glycolysis is partly controlled by feedback
  regulation of the enzyme phosphofructokinase
• Phosphofructokinase has two allosteric sites
• An inhibitor site that binds ATP (at very high
  ATP levels)
• An activator site to which AMP binds (when ATP is
  low)

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KEY CONCEPTS 8.2

• Aerobic respiration consists of four stages
  glycolysis, formation of acetyl coenzyme A, the
  citric acid cycle, and the electron transport
  chain and chemiosmosis

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Animation Recreating the reactions of glycolysis
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Nutrients Other Than Glucose

• Nutrients other than glucose are transformed into
  metabolic intermediates that enter glycolysis or
  the citric acid cycle
• Amino acids
• The amino group (NH2) is removed (deamination)
• The carbon chain is used in aerobic respiration
• Lipids
• Glycerol is converted to a compound that enters
  glycolysis
• Fatty acids are converted by ß-oxidation to
  acetyl CoA, which enters the citric acid cycle

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PROTEINS
CARBOHYDRATES
FATS
Fatty acids
Amino acids
Glycerol
Glycolysis
Glucose
G3P
Pyruvate
Energy from Proteins,Carbohydrates, and Fats
CO 2
Acetyl coenzyme A
Citric acid cycle
Electron transport and chemiosmosis
End products
NH3
H2O
CO2
Fig. 8-13, p. 187
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Anaerobic Respiration

• anaerobic respiration
• Does not use oxygen as the final electron
  acceptor
• Used by prokaryotes in anaerobic environments,
  such as waterlogged soil, stagnant ponds, and
  animal intestines
• Electrons from glucose pass from NADH down an ETC
  coupled to ATP synthesis by chemiosmosis
• End products of this of anaerobic respiration are
  CO2, one or more reduced inorganic substances,
  and ATP

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Fermentation

• fermentation
• An anaerobic pathway that does not involve an ETC
• Only two ATPs are formed per glucose (by
  substrate-level phosphorylation during
  glycolysis)
• NADH molecules transfer H atoms to organic
  molecules, regenerating NAD needed for
  glycolysis
• Fermentation is highly inefficient, because fuel
  is only partially oxidized

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Alcohol Fermentation

• Yeasts are facultative anaerobes that carry out
  aerobic respiration when oxygen is available but
  switch to alcohol fermentation when deprived of
  oxygen
• alcohol fermentation
• Enzymes decarboxylate pyruvate, forming
  acetaldehyde
• NADH produced during glycolysis transfers
  hydrogen atoms to acetaldehyde, reducing it to
  ethyl alcohol

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Lactate Fermentation

• Certain fungi bacteria perform lactate
  fermentation vertebrate muscle cells also
  produce lactate when oxygen is depleted during
  exercise
• lactate (lactic acid) fermentation
• NADH produced during glycolysis transfers
  hydrogen atoms to pyruvate, reducing it to lactate

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Fermentation
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Aerobic Respiration, Anaerobic Respiration, and
Fermentation
Table 8-2, p. 188