The Design of Metabolism...
Cellular Energetics & Chemical Equilibrium |
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Biological Order and Cell Energy Transformations |
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ENERGY TRANSFORMATION within CELLS
is
ABILITY TO DO WORK...
2 kinds
of traditional energy:
1. Potential Energy... stored energy, due to mass in position
2.
Kinetic Energy
(energy of movement)
ex:
heat
(thermal) energy
which flows from higher heat
or greater molecular motion to lower heat content;
radiant energy
kinetic energy of photons (light);
when molecules absorb light radiant --> thermal
chlorophyll --light-->
ATP in photosynthesis
mechanical energy
- push/pull of cytoskeletal filaments
electrical energy
- energy of moving electrons |
read pages 54-60 |
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energy also occurs in such cellular forms as:
chemical concentrations gradients
across
membranes
can
diffuse from [higher] to [lower]
electrical gradients (potential
differences)
across
membranes
a
separation of charge
as much
as 200,000 volts per cm |
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THERMODYNAMICS:
the SCIENCE of ENERGY TRANSFORMATIONS |
1st Law of Thermodynamics...
Energy can neither be
created nor destroyed,
but is convertible.
nuclear
blast
- mass of U235 --> heat/light
photosynthesis --> sunlight into
glucose bonds
muscle --> hydrolysis of ATP in
contractions |
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all forms of energy are inter-convertible thus all are
expressed in same
units of
measure
Joule,
but biologists use more common
calorie
[heat
é
1gm 1oC]
1 Kcal = 1,000 cal =
4.184
Joule
[1 cal = 4.184 J]
2nd Law of
Thermodynamics…
ENTROPY
is
commonly referred to as a measure of degree of order of the Universe,
and thus its randomness
(Entropy = disorder)
CAN ONLY INCREASE
The Rules of the Universe are simple:
Cities crumble, Stars go Supernova, and
we are all equlibrium...izing (dying)
Entropy*
is maximum disorder..... "heat"
Events
in the Universe have a direction
--->
MAX ENTROPY
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According to Laws of Thermodynamics, biological systems
should proceed
with a loss of energy toward a greater degree of disorder
Yet, WOW! … Cells
are highly ordered...
and life appears to go from more simple to more complex
wings of a bird, human eye,
spider’s web
and all cells - feed, grow,
and differentiate
HOW...
in light of the 2nd law of thermodynamics
?
Entropy must increase (heat); yet disorder within
one part of Universe
can decrease at the greater expense of the Total
Surroundings.
ENERGY IN ----> CELL STRUCTURE ----> ENERGY OUT
What we need to be able to do is
measure
Energy
in systems, esp. energy able to do work
Willard Gibbs
(1839-1903)
applied the principles of
Thermodynamics
to chemical systems
to determine the energy content and changes within a chemical reaction
and derived the...
FREE ENERGY EQUATIONS
DG
= DH - T
DS  *
free energy enthalpy entropy
DG is a numerical measure of how far a reaction is
from equilibrium
DG is measure amount energy in system able to do work (to
stay away from equilibrium)... Disorder increases (thus entropy increases)
when useful energy,
that which could be used to do work,
is dissipated as heat...
biological
systems are are ISOTHERMAL, e.g., held at constant
temp/pressure
(4o to
@ 45o
) and thus in biological systems
DH
@
0
-
What Gibbs showed was that "cell chemical systems change so that
Free Energy is minimized"
- thus, DG
can PREDICT..... the Direction of Cellular Reactions......
TOWARD EQUILIBRIUM and
to Maximum ENTROPY
Any
natural process occurs spontaneously, if and
only if,
the associated change in
G for
the system is negative (ΔG
<
0).
when -DG
is negative a reaction is
spontaneous,
R --> P,
& there is a
increase in entropy
Likewise, a system reaches equilibrium when the associated change in
G
for the system is zero
(ΔG
=
0),
and no
spontaneous process can occur, if the change in
G is
positive (ΔG
>
0).-
-
CHEMICAL REACTION A <---> B Which Way?
DG = DG0’ + R
T ln [
p]/[
r]
change in free energy content of a reaction...depends upon:
1. energy is stored in molecule's covalent bonds
2. remember, temperature is negligible... cells are isothermal, i.e.,
DG = actual free energy
DGo' = standard free energy [change under standard conditions:
25oC (298 K),
1 atmosphere, reactants @ 1 [M], & pH 7.0]
R =
gas constant ( 1.987 x 10-3 Kc/mol)
T =
absolute temp (273oK); thus @ 25oC
= 298oK
ln =
natural log (conversion to log10 = 2.303)
but, at equilibrium DG = 0
and we'll say the [p]/[r] =
Keq
-
if we solve above equation for
DGo' we can
see the relationship of Keq to
DGo’
-
-
Free Energy Equation...
ΔG
=
ΔG0’
+ RT ln [P]
[R]
@ equilibrium
ΔG
= 0
.... thus rearranging
ΔG0’
= - RT ln [P]
[R]
@ equilibrium
[P]
=
Keq
[R]
@ 250C
... -RT ln Keq
= -(2.0) (298) (2.303) lg10 Keq
= -[1364] lg10
Keq
thus..........
ΔG0’
= - [1364] lg10
Keq
-
The
difference between...
DG
and
DG0’
DG
is determined by the concentrations present
at that time,
& is a measure of how far a reaction is
from equilibrium then.
Cell metabolism is essentially
a
non-equilibrium condition.
DG0’
is a fixed value for a
given reaction under standard conditions of 250C,
1 atm, pH 7.0, and [1M initial reactants & products], & indicates in which
direction a reaction will proceed under standard
conditions, i.e., is it +/-.
standard conditions
do not exist within a cell, thus
DG
must be
used to predict the direction of a
cellular reaction at a given time.
µ Metabolism works by changing the relative concentrations of reactants
and products to favor the progress of
unfavored reactions to completion.
-
-
-
Relationship between Keq & DG0’
DG0’
= - [1364] lg10 Keq
|
products
reactants |
Keq
|
lg10 |
DG0’
cal/mole
[ lg10 x -1364
] |
[R] > [P] |
|
1/1000 |
.001 |
10-3 |
-3 |
+ 4092 |
|
1/100 |
.01 |
10-2 |
-2 |
+ 2728 |
|
1/10 |
.1 |
10-1 |
-1 |
+ 1364 |
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1/1 |
1.0 |
0 |
0 |
0 |
[R] = [P]
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10/1 |
10 |
10+1 |
+1 |
- 1364 |
[P] > [R] |
|
100/1 |
100 |
10+2 |
+2 |
- 2728 |
|
1000/1 |
1000 |
10+3 |
+3 |
- 4092 |
|
rx #5 pg 482 |
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Which way this reaction
goes is dependent upon existing concentrations? |
DG0’
@ cell [equilibrium]
the
Keq of
DHAP/G3P =
22.4
DG0’
=
- [1364] lg10
22.4
=
- [1364] (1.35)
=
- 1,842 cal/mole |
DG
=
DG0’
+ RT ln [P]
/ [R]
but, when DHAP =
0.001M
& G3P =
0.1M
DG =
-1842 c/m + (-1364) (lg10
0.01)
=
(-1842) +
(-1364)(-2) = + 886 cal/mole |
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Thus under standard condition
the reaction is favored from G3P
toward DHAP (-DG),
but under a
specific cellular condition, where the
ratio of
reactant & products is changed,
the reaction may not be favored,
and will go in other direction from DHAP to
G3P..
This
is what happens in
glycolysis*, the
pathway shifts ratios and pulls
rx to G3P.
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-
-
-
-
-
-
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CHEMICAL REACTIONS
A <---->
B
Which way depends on the free energy...
EXERGONIC REACTION - is one which releases free energy
Product [B] <<<
energy REACTANT
[A] [stored in covalent bonds]
ex: burning wood (cellulose)
glucose monomers = potential energy
breaks bonds, release heat & light ---> CO2
& H2O
cell respiration - (heterotrophy)
- cellular burning of
glucose
slower, multi-step process to capture & release
energy.... as ATP
fig 2.29*
ENDERGONIC REACTION - requires input of energy for
A -->
B
PRODUCT
[B] >>>energy
Reactant
[A]
ex:
photosynthesis - (autotrophy)
glucose made from CO2 +
H2O --light---> C6H12O6
energy poor vs. energy
rich
Many biological systems lead
to an increase in order... decrease in entropy (
DS
< 0)?
How does Metabolism create more order in
cellular chemical reactions?
COUPLED
REACTIONS - involves say... the linking of the hydrolysis
of ATP
(a favored reaction)
to a thermodynamically unfavored reaction,
thereby creating
some biological
order (greater molecular structure).
if
DG
for the reaction B + C -->
D is +,
but if it is less than the
DG
of ATP hydrolysis,
then the reaction
may be driven to
completion by coupling.
synthesis of glutamine*
most cells use
ATP hydrolysis energy and couple it to
processes as:
conformational changes in enzyme, as
kinases, which phosphorylate
proteins converting then from inactive to active (& vice versa);
energy gained in the stressed conformation is released,
when the protein relaxes.
Design of Metabolism:
metabolism is
run via enzyme catalyzed
metabolic pathways*
which can get very complex...
ecb fig 3.2
& Kegg fig*
2 Categories of metabolic reactions:
Anabolic - biosynthesis in
autotrophs
coupling
of reactions that are energetically
unfavorable,
with reactions that are energetically
favored
done by linking
ATP
hydrolysis* (favored) to reactions
Catabolic - cell respiration in
heterotrophs
oxidation (removal) of e-’s from foodstuffs
3 steps:
1. Digestion of polymers (foods)
into monomers
2. GLYCO-LYSIS ---> AcoA splits sugar monomers
3. Oxidation of AcoA ---> CO
2 + NADH ---> H
2O
ADP + P ---> ATP
µ
linking pathways together (not
favored), creates
new biological order
[ecb
3.3]
Design of Metabolism... or how biological order comes about...
via a
balance of
Endergonic
&
Exergonic
reactions.
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| Autotrophs:
endergonic |
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light energy... is converted into covalent chemical bond energy |
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e- |
|
CO2 |
oxidized form |
H2O
ATP
+
NADPH |
more energetically stable
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CH2O |
less energetically stable |
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H+ |
reduced form |
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| Heterotrophs:
exergonic |
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food stuffs [CH2O]n
CO2
+
H2O
+
ATP |
| NAD+
NADH |
Balance between photosynthesis &
respiration
-->
ecb 3.10 |
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Key Cell energy
intermediates-
NADH &
NADPH,
FAD, &
ATP |
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Design of metabolism...
OXIDATION / REDUCTION -
Redox Reactions
are a major energy capture mechanism
e-
&/or
H+ transferred between oxidized & reduced forms
of e- carrier coenzymes
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AH
A
+
e- +
H+
|
oxidation -
removal of e-
from substrate
oxidation states
reduction
- gaining of e- (& often a proton,
H+)
| NAD
+
respiration
NADH |
6O2
+ C6H12O6
6CO2
+ 6H2O |
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NADP+
photosynthesis NADPH |
KEY METABOLIC REACTIONS:
6 major categories of bio-chemical reactivity
Bio-chemical reactivity
is bond breaking & reforming
these are violent events inside cells, carefully controlled by
ENZYMES |
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1. redox reaction (oxidation/reduction) PGAld + NAD+ <--> 1,3di-PGA + NADH |
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oxidoreductases (dehydrogenases) |
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2. functional group transfers glu + ATP <--> G6P + ADP |
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transferases |
| 3. Hydrolysis
glu-glu(n) + H
2O <--> glu-glu(n-1) |
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hydroylases |
| 4. C-C breaking or re-formation fruc1-6bP <--> DHAP + 3PGAld |
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lyases |
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5. rearrangement (isomerizations) glucose-6P <--> fructose-6P |
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isomerases |
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6. Condensations
protein(n) + aa
1 <--> protein(n+1) + H
2O |
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transferase |
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the work horses of metabolism (life) are these enzymes... |
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