Section 5: Bioenergetics

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Section 5 Bioenergetics

• 1. Bioenergetics Metabolism

10/4/05
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Bioenergetics biological processes

• How do organisms use energy to sustain life?
• for most organisms, energy is derived from
  energy-producing chemical reactions
• these reactions form a network known as
  metabolism
• living organisms
• constantly exchange matter energy with their
  surroundings an open system
• steady state input output
• most reactions not at equilibrium catalyzed,
  rate-controlled by enzymes

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Bioenergetics biological processes

• enzymes accelerate reactions, but net reactions
  do not occur unless they are
• energetically favorable (energy-producing)
• or coupled to an energetically favorable process
• processes in biology
• chemical reactions
• motility
• transport
• diffusion
• spontaneous process occurs without net energy
  input with net energy output

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changes in reactants products
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Bioenergetics free energy

• knowledge of energy is important since energy is
  related to
• how much biological work a process can do or
  energy a process requires
• what direction a process will go spontaneously
• how far a process will go in that direction
• how fast it will go in that direction (related to
  free energy of activation, DG )
• of the various forms of energy, free energy (G)
  is used in biochemistry since it relates most
  directly to these questions
• what direction how far a reaction will go is
  determined by the difference between GProducts
  GSubstrates(GP GS, respectively)

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Free (available) energy

• DG GP GS
• DG is
• independent of the path from S to P
• not changed by catalysts
• unrelated to how fast
• magnitude of DG determines
• how far reaction is from equilibrium
• how much energy is available/required
• sign () of DG determines
• what direction
• whether energy is
• available from the reaction or
• required to drive the reaction
• (slide 6)

S
GS
free energy
DGuncat
DGcat
S
GS
???DG ?
P
GP
progress of reaction
adapted from Fig. 8.3
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DG how far from equilibrium

• DG aka chemical potential
• DG that is available to do work is dependent on
  the concentrations of reactants products
• e.g., a general reaction A B C D eq. 1
• reactants products
• for this reaction eq. 2
• where DG ' free energy change at pH 7
• DG ' o standard free energy change at pH 7
• T temperature in degrees Kelvin (K)
• R gas constant 1.98 cal/mol/K
• products / reactants ratio (p/r ratio)

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DG' reaction direction

• if DG '
• lt 0, net reaction, as written, goes to right
  exergonic energy yielding spontaneou
  s
• 0, equilibrium no net reaction
• gt 0, net reaction, as written, goes to left
  endergonic energy requiring
• if eq. 1 written in opposite direction D
  C B A then DG ' has same magnitude, opposite
  sign
• sign shows direction reaction can go ( to
  right to left)
• under standard conditions, reactants
  products 1 Mso RT term of eq. 2 0, and
  DG ' DG ' o

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DG' equilibrium

• at equilibrium, DG ' 0 eq. 2 becomes
• DG ' o RT 2.3 1og ( )
• DG ' o RT 2.3 1og K' eq. 3
• where K' is the equilibrium constant at pH 7
• standard free energies
• DG ' o lt 0 indicates that at equilibrium
  products gt reactants (p/r ratio gt1)
• DG ' o gt 0 indicates that at
  equilibrium reactants gt products (p/r ratio
  lt1)

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Relation between DG' o and K'

• K' DG ' o (25ºC)
• kcal/mol kJ/mol
• 104 5.46 22.84
• 103 4.09 17.11
• 102 2.73 11.42
• 101 1.36 5.69
• 1 0 0
• 10 1.36 5.69
• 102 2.73 11.42
• 103 4.09 17.11
• 104 5.46 22.84
• 10-fold change of K' 1.4 kcal/mol difference of
  DG' o
• larger K' corresponds to more negative DG' o

cf. Table 8.4
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2
DG ' o
0
2
4
10 1
10 3
10 1
10 3
1
K'
DG ' o RT 2.3 1og K'
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DG' coupling reactions

• like reactions, standard free energies can be
  added to get information about new reactions.
  For example,
• DG ' o
• (kcal/mol)
• H2O ATP ADP Pi 7.3
• and
• glucose Pi glucose 6-phosphate H2O 3.3
• adding the reactions their DG ' o values
• glucose ATP ADP glucose 6-phosphate 4.0
• note that when the 2 reactions are added, H2O
  Pi "cancel out"

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DG' coupling reactions (cont'd)

• at equilibrium, DG' 0, so at 25o C (or 298 K)
• using eq. 3, K' can be calculated
• 4.0 kcal/mol RT 2.3 log K'
• and K' 9 102
• this verifies that the summed reaction tends to
  go to the right
• at equilibrium, p/r is high
• glucose is phosphorylated because an enzyme
  exists that couples the reactions
• enzyme hexokinase related enzymes

ADPglucose 6-PATPglucose
900
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Energy coupling
A
Alberts et al.,Fig.2-17
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Energy coupling
B
A
Alberts et al.,Fig.2-17
part of the kinetic energy is used to lifta
bucket of H2O, a correspondinglysmaller amount
is transformed into heat
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Energy coupling
B
A
Alberts et al.,Fig.2-17
C
part of the kinetic energy is used to lifta
bucket of H2O, a correspondinglysmaller amount
is transformed into heat
the potential energy stored in the elevated
bucket of H2O can be used to drive a wide
variety of different machines
hydraulicmachine
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Energy coupling
Lehninger 4edFig 1-26a
Lehninger et al., 4ed. Fig 1-26a
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Coupling in cells the ATP-ADP cycle

• Catabolism Biological work
• glycolysis ATP
• Krebs cycle oxidative 1. mechanical
• fatty acid phosphor- 2. synthetic
  (anabolism)
• oxidation ylation ADP 3. active
  transport
• etc. Pi 4. signal amplification
• the ATP cycle couples catabolism to biological
  work
• catabolism drives biological work via the ATP
  cycle
• catabolism drives ATP synthesis
• ATP hydrolysis drives biological work

cf. Fig. 14.8
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aka the ATP cycle
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Overview of catabolism
FATS
POLYSACCHARIDES
PROTEINS
Stage 1
amino acids
fatty acids,glycerol
glucose,other sugars
Stage 2
acetyl CoA
CoA
H2O O2
Stage 3
eCO2
Krebscycle
oxidativephosphorylation
v
v
ATP ADP Pi
adapted from Fig. 14.12
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Overview of metabolism

• endergonic processes driven by coupling to
  exergonic processes
• ATP most common energy carrier (energy
  "currency")
• generated from oxidation of fuel molecules
  (catabolism)
• in catabolism, a wide variety of fuel molecules
  degraded to a few simple units
• in anabolism (biosynthesis), a wide variety of
  biomolecules made from a few building blocks
  (precursors)
• activated carriers (precursors)
• catabolic anabolic pathways distinct allows
  both to be
• energetically favorable controlled
  independently
• pathways compartmented

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Features of metabolic pathways

• function, role, significance
• location (compartment)
• reactions (individual steps)
• committed step
• control
• mechanism
• activators, inhibitors
• connections with other pathways
• stoichiometry, including ATPs yielded/used
• variations among cells/organs/organisms, etc.

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Compartmentation of cell processes

• cell component pathway or process
• cytosol glycolysis (6) gluconeogenesis (6)
  pentose phosphate pathway (6) activation of
  amino acids (3) fatty acid synthesis (7)
  nucleotide synthesis (8)
• endoplasmic glycoprotein synthesis
  (11)reticulum steroid synthesis
  (7) packaging of biosynthetic products (11)
• glycogen enzymes of glycogen synthesis
  granules degradation (6)
• Golgi complex formation of membranes (7)
  secretory vesicles (11) packaging for export
  (11)
• lysosomes segregation of hydrolytic enzymes
  such as ribonuclease acid phosphatase (12)

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refer to course sections
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Compartmentation of cell processes

• cell component pathway or process
• peroxisomes site of amino acid oxidases, urate
  (microbodies) oxidase (8), peroxidases
  catalase (10)
• mitochondria Krebs cycle (6) electron transport
  oxidative phosphorylation (5) fatty acid
  ox- idation (7) amino acid catabolism (8)
• nucleus replication of DNA (3) synthesis of
  tRNA, mRNA, some nuclear proteins (3, 9)
• plasma energy-dependent transport systems
  membrane such as Na,K transporting ATPase
  amino acid glucose transport systems (10)
• ribosomes protein synthesis (3, 11)

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Cell compartments
vacuole
mitochondrion
cytosol
cytoskeleton
nuclearenvelope
nucleus
nucleolus
plasmamembrane
Golgi vesicle
Golgi sacs
smooth ER
rough ER
lysosome
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Rawn, Fig. 1-8
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Free energy summary

• DG '
• available energy
• maximum energy available to do work
• chemical potential
• driving force
• DG ' º
• characteristic of a reaction (see Table on next
  slide)
• indicates tendency for reactants products
  or products reactants
• group-transfer potential
• log expression of K' (DG ' º RT 2.3 log K')
• if large negative
• energy-rich, high-energy, high group-transfer
  potential
• indicates stabilization of products relative to
  reactants

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DG'º of hydrolysis of selected phosphates(group
transfer potential phosphoryl group to H2O)

• Compound DG'o (kcal/mol) (Stryer,Table 17-1)
• phosphoenolpyruvate (PEP) 14.8 X-P H2O
• carbamoyl phosphate 12.3 XH P-OH
• acetyl phosphate 10.3
• creatine phosphate 10.3
• pyrophosphate 8.0
• ATP (to ADP) 7.3
• glucose 1-phosphate 5.0
• glucose 6-phosphate 3.3
• glycerol 3-phosphate 2.2
• Effect of coupling 2 of the above 14.8
  (7.3)
• PEP ADP pyruvate ATP 7.5

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Large DG'º ATP structure

• ATP hydrolysis DG ' º 7.3 kcal/mol
• means reaction tends to go far to the right
• structural basis relative to ATP, ADP Pi
• are more resonance stabilized
• are more solvated (solvent stabilized)
• have less charge repulsion
• release an H (which combines with bases)

at equilADPPi 300x300 ATP 1

actual p/r in cells 1/104
-7.3 1.4xlog(104)13
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DG' effect of change in concentrations of
reactants products

• ADP Pi ATP p/r DG'
• mM mM mM ratio
• 0.25 2 5 95 10-4 12.9 rest
• 2.25 4 3 57 .003 11.0
• 4.25 6 1 19 .025 9.5
• 5.2 7 .05 1 .73 7.4 rigor
• 5.25 7 10-4 .004 105 0 equilibrium

100ATP/(ATP ADP)
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DG'º of selected biochemical reactions

• DG ' oReaction type (kcal/mol)
• Hydrolysis reactions
• maltose H2O 2 glucose 3.7
• sucrose H2O glucose fructose 7
• glycylglycine H2O 2 glycine 2.2
• Rearrangement
• glucose 1-phosphate glucose
  6-phosphate 1.7
• Oxidation with molecular oxygen
• NADH H ½ O2 NAD H2O 53 glucose
  6 O2 6 CO2 6 H2O 686 palmitic acid
  23 O2 16 CO2 16 H2O 2,338

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Next2.Oxidation-reduction reactionsElectron
transport