Bioenergetics
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
Living cells, organisms
matter
energy
1
metabolism
bioenergetics
(transduction)
matter
energy
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
* changes in [reactants] & [products]
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)
Free (available) energy
DG = GP – GS
 DG is:
independent of the path from S to P
not changed by catalysts
unrelated to how fast
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
 magnitude of DG determines
GS
DG‡uncat
DG‡cat
S

DG
GP

progress of reaction
adapted from Fig. 8.3
P
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
for this reaction:
eq. 2
reactants  products
where
DG '
DG' o
[C] [D]
DG ' = DG' + RT 2.3 log ([A] [B] )
o
= free energy change at pH 7
= standard free energy change at pH 7
T
= temperature in degrees Kelvin (K)
R
= gas constant = 1.98 cal/mol/K
[C] [D]
[A] [B]
= [products] / [reactants] ratio (p/r ratio)
DG' & reaction direction
 if DG'
< 0, net reaction, as written, goes to right
= 0, equilibrium; no net reaction
> 0, net reaction, as written, goes to left
exergonic
energy yielding
spontaneous
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 M
so RT… term of eq. 2 = 0, and
DG' = DG' o
DG' = DG' + RT 2.3 log
o
(
[C] [D]
[A] [B]
)
DG' & equilibrium
at equilibrium, DG' = 0
o
DG' = DG' + RT 2.3 log (
o
[C] [D]
[A] [B]
)
& eq. 2 becomes
DG' = –RT 2.3 1og
(
[C]eq [D]eq
[A]eq [B]eq
)
DG' o = –RT 2.3 1og K' eq. 3
where K' is the equilibrium constant at pH 7
standard free energies:
DG' o < 0 indicates that at equilibrium
[products] > [reactants] (p/r ratio >1)
DG' o > 0 indicates that at equilibrium
[reactants] > [products] (p/r ratio <1)
Relation between DG' o and K'
10–4
10–3
10–2
10–1
1
10
102
103
104
DG' o (25ºC)
kcal/mol kJ/mol
5.46
4.09
2.73
1.36
0
–1.36
–2.73
– 4.09
–5.46
22.84
17.11
11.42
5.69
0
–5.69
–11.42
–17.11
–22.84
cf. Table 8.4
4
2
DG' o
K'
0
–2
–4
10 – 3
10 – 1
1
10 1
 10-fold change of K' 1.4 kcal/mol difference of DG' o
K'
 larger K' corresponds to more negative DG' o
DG' o = –RT 2.3 1og K'
10 3
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"
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
[ADP][glucose 6-P]
[ATP][glucose]
glucose is phosphorylated because an enzyme
exists that couples the reactions
enzyme: hexokinase & related enzymes
= 900
Energy
coupling
Alberts et al.,
Fig.2-17
A
Energy
coupling
A
B
Alberts et al.,
Fig.2-17
part of the kinetic energy is used to lift
a bucket of H2O, & a correspondingly
smaller amount is transformed into heat
Energy
coupling
A
B
Alberts et al.,
Fig.2-17
C
part of the kinetic energy is used to lift
a bucket of H2O, & a correspondingly
smaller amount is transformed into heat
hydraulic
machine
the potential energy stored in the elevated
bucket of H2O can be used to drive a wide
variety of different machines
Energy
coupling
Lehninger et al., 4ed. Fig 1-26a
12
Coupling in cells: the ATP-ADP cycle*
Catabolism
glycolysis
Krebs cycle
fatty acid
oxidation
etc.
Biological work
ATP
oxidative
phosphorylation
ADP
+ Pi
1.
2.
3.
4.
mechanical
synthetic (anabolism)
active transport
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
13
*aka the ATP cycle
Overview of catabolism
FATS
POLYSACCHARIDES
PROTEINS
Stage 1
fatty acids,
glycerol
glucose,
other sugars
amino acids
Stage 2
acetyl CoA
oxidative
phosphorylation
ATP ADP + Pi
14
CoA
O2
e–
CO2
Stage 3
v
H2O
Krebs
cycle
v
adapted from Fig. 14.12
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
15
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.
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)
glycoprotein synthesis (11);
steroid synthesis (7);
packaging of biosynthetic products (11)
enzymes of glycogen synthesis &
degradation (6)
formation of membranes (7) & secretory
vesicles (11); packaging for export (11)
segregation of hydrolytic enzymes such
as ribonuclease & acid phosphatase (12)
endoplasmic
reticulum
glycogen
granules
Golgi complex
lysosomes
Compartmentation of cell processes
cell component
pathway or process
peroxisomes
(microbodies)
mitochondria
site of amino acid oxidases, urate
oxidase (8), peroxidases & catalase (10)
Krebs cycle (6); electron transport &
oxidative phosphorylation (5); fatty acid oxidation (7); amino acid catabolism (8)
replication of DNA (3); synthesis of tRNA,
mRNA, some nuclear proteins (3, 9)
energy-dependent transport systems
such as Na+,K+ transporting ATPase;
amino acid & glucose transport systems (10)
protein synthesis (3, 11)
nucleus
plasma
membrane
ribosomes
Cell compartments
vacuole
cytosol
nuclear
envelope
nucleus
mitochondrion
cytoskeleton
nucleolus
rough ER
19
plasma
membrane
Golgi vesicle
Golgi sacs
smooth ER
lysosome
Rawn, Fig. 1-8
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
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:
PEP + ADP  pyruvate + ATP
–14.8 + (+7.3)
–7.5
Large –DG'º & ATP structure
DG' = DG' o + RT 2.3 log (
 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)
O
O
O
O
[C] [D]
[A])[B]
at equil
[ADP][Pi] 300x300
[ATP]
1 
actual p/r in cells:
4
-7.3 + 1.4xlog(10–4)–13
O
O
–
–
R O P O P O P O–
R O P O P O + H O P O + H+
O – O – O – H2O
O– O–
O–
22
How does ATP work ?
Organisms use enzymes to
break down energy-rich
glucose to release its
potential energy
This energy is trapped and
stored in the form of
adenosine
triphosphate(ATP)
Copyright Cmassengale
26
How Much ATP Do Cells Use?
It is estimated
that each cell
will generate
and consume
approximately
10,000,000
molecules of
ATP per second
Copyright Cmassengale
27
Coupled Reaction - ATP
The exergonic
hydrolysis of ATP
is coupled with
the endergonic
dehydration
H2O
process by
transferring a
phosphate group
to another
H2O
molecule. Copyright Cmassengale
28
Hydrolysis of ATP
ATP + H2O 
ADP + P
(exergonic)
Adenosine triphosphate (ATP)
P
P
P
Hydrolysis
(add water)
P
P
+
P
Adenosine diphosphate (ADP)
Copyright Cmassengale
29
Hyrolysis is Exergonic
Energy
Used
by
Cells
Copyright Cmassengale
30
Dehydration of ATP
ADP + P  ATP + H2O
(endergonic)
Dehydration
(Remove H2O
P
P
+
P
Adenosine diphosphate (ADP)
Adenosine triphosphate (ATP)
P
Copyright Cmassengale
P
P
31
Dehydration is Endergonic
Energy
is
restored
in
Chemica
l Bonds
Copyright Cmassengale
32
DG': effect of change in concentrations of reactants &
products
DG' =
23
[ADP]
mM
[Pi]
mM
0.25
2
2.25
4.25
5.2
5.25
4
6
7
7
DG' o
[C] [D]
+ RT 2.3 log ( [A] [B])
[ATP]
mM
%*
p/r
ratio
5
95
10-4
12.9
rest
3
1
57
19
1
.004
.003
.025
.73
105
11.0
9.5
7.4
0
rigor
equilibrium
.05
10-4
* 100×[ATP]/([ATP] +[ADP])
–DG'
DG'º of selected biochemical reactions
Reaction type
DG' o
(kcal/mol)
Hydrolysis reactions
maltose + H2O  2 glucose
sucrose + H2O  glucose + fructose
glycylglycine + H2O  2 glycine
–3.7
–7
–2.2
glucose 1-phosphate  glucose 6-phosphate
–1.7
Rearrangement
Oxidation with molecular oxygen
NADH + H+ + ½ O2  NAD+ + H2O
glucose + 6 O2  6 CO2 + 6 H2O
palmitic acid + 23 O2  16 CO2 + 16 H2O
24
–53
–686
–2,338
High
Energy
Low
Energy