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1
BI25M1
ENERGY
TRANSFORMATIONS
LECTURE 1
AIMS: To review:
the nature of energy;
the ways in which living organisms
transform energy from one form to
another.
[Lehninger (Edition 4) pp.21-27 and Chapter 13
Lehninger (Edition 5) pp.19-26 and Chapter 13
Instant Notes
Section C2]
2
1 ENERGY IS THE CAPACITY TO DO
WORK.
Kinetic energy is to do with movement.
Some examples:
Type of
energy
What moves
Example of work
done
heat
molecules
steam engine
light
photons
photosynthesis
electrical energy
electrons
household appliance
mechanical energy any moving
object
bicycle pedal
Potential energy is energy stored in matter
because of its location or structure.
Some examples:
water in dam
energy stored because of its altitude
complex molecule energy stored in arrangement of atoms
3
2 ENERGY MAY BE TRANSFORMED
FROM ONE FORM TO ANOTHER.
Some examples:
potential energy
of water in dam
to
electrical energy
sunlight
to
potential energy of
complex molecules
in photosynthesising plant
3 ENERGY
TRANSFORMATIONS
ARE SUBJECT TO TWO LAWS OF
THERMODYNAMICS.
1 Energy, although transformable from
one form to another, cannot be created
or destroyed.
2 All energy transformations ultimately
increase the entropy
(disorder/ randomness) of the universe.
4
4 LIVING ORGANISMS ORIGINATED,
EVOLVED AND EXIST BECAUSE OF
ENERGY TRANSFORMATIONS.
Life must have originated like this:
simple abiotic
molecules
taken into
‘organism’
simpler
molecules
chemical
conversion
(‘food molecules’)
(‘excretory products’)
some potential energy
zero potential energy
energy released
some energy ‘saved’
and used by
the organism
some energy ‘lost’
and returned to
environment as heat
to allow energy-requiring
biosynthesis
to allow energy-requiring
activity e.g. locomotion,
reproduction, etc
simple molecules
zero or low
potential energy
complex molecules
of which the organism is built
high potential
energy
5
5 DURING EVOLUTION, THE RANGE
OF HIGH POTENTIAL ENERGY
‘FOOD MOLECULES’ WIDENED.
Some present-day micro-organisms still
use very simple, inorganic ‘food
molecules’, which are converted into lower
potential energy forms as just described.
Examples are bacteria that live in hot sulphur
springs. They carry out this reaction:
FeS
+
H2S
FeS2
+
H2
energy released
Other organisms evolved the capacity to
synthesise complex molecules from very
simple precursors (‘photosynthesis’):
sunlight
(light energy)
CO2
H2O
complex molecules used to as
form the structure of the organism
zero
potential energy
high
potential energy
6
Still other organisms evolved the capacity
to use such biologically-synthesised
complex molecules themselves as ‘food
molecules’:
complex biomolecules
excretory products
high
potential energy
zero
potential energy
To summarise:
for most present-day organisms,
sunlight is the ultimate ‘source’ of energy.
It, through many transformations,
enables organisms to be constructed,
and to be biologically active.
7
6
ALTHOUGH LIFE INVOLVES
CONSTRUCTING LOW ENTROPY
SYSTEMS, THIS OCCURS WITHIN A
LARGER SYSTEM, IN WHICH
ENTROPY INCREASES.
Life involves complexity and organisation at
a number of levels:
whole body
organs and tissues
cells
subcellular compartments/organelles
molecules
all of which are highly ordered.
This contrasts with the generally simpler,
less organised arrangements in inanimate
matter: rock, soil, air, water.
Thus, building and maintenance of the
structure of living organisms involves a
decrease in entropy (disorder/randomness).
8
A closer look at the energy flow through
the organism, however, shows how life
occurs with an increase in entropy of a
larger system, consisting of the organism
within its surrounding environment.
complex
‘food
molecules’
simple
molecules
simple
molecules
used for
biosynthesis
very
simple
excretory
molecules
used for
biosynthesis
energy
‘lost’ as heat
‘saved’
‘saved’
used in
various
activities
energy
energy
‘lost’ as heat
simpler
molecules
‘saved’
used in
various
activities
energy
‘lost’ as heat
complex
molecules
used in
various
activities
‘lost’ as heat
complex
molecules
The overall process may be summarised thus:
complex molecules
of high potential
energy taken from
the environment
simple molecules
of zero potential
energy returned to
the environment
more order
(low entropy)
less order
(high entropy)
potential energy
of the complex molecules
heat energy
9
To summarise:
building and maintaining the structure of
an organism involves constructing a highly
complex, organised, low entropy system.
Viewed in isolation, this seems to go against
the second Law of Thermodynamics
(Section 3).
However, as we have seen, the process is
possible because it does not occur in
isolation. When organism and surroundings
are considered together, the process is seen
to occur with an increase in the entropy of
the
larger
(organism/surroundings)
combination.
Put another way, life,
(like all other processes occurring in the
universe),
ultimately involves making the universe
more random.
10
7 HEAT IS THE LOWEST ‘GRADE’ OF
ENERGY.
When energy flows through an organism,
some is ‘saved’, and used for biosynthesis
and activity of the organism (Sections 4, 6).
However, in any energy-transforming
machine, not all the energy transformed
can be turned into useful energy. Some
becomes less useful energy and is ‘lost’.
Living organisms are no exception. At each
stage of the flow of energy through them,
some energy is ‘lost’ back to the
environment, generally as heat (Sections 4,
6).
Eventually, as we have seen, (Section 6) all
the energy, originally potential energy of
‘food
molecules’,
returns
to
the
surroundings, largely as heat.
11
Why is heat a ‘lower grade’, ‘less useful’
form of energy?
All forms of energy ‘do work’ (Section 1),
but heat energy only does this when it flows
from a place with a high temperature to
one with a low temperature.
Many systems are not like this,
and organisms/cells certainly aren’t.
So heat in general is not a useful form of
energy for living organisms. It may warm a
body up, but it can’t readily be
transformed into other energy forms.
To summarise:
an abbreviated version of energy flow into,
through and out of the biosphere is:
light
energy
(of sun)
chemical
potentia
energy
(of biomolecules)
heat
energy
12
8 ‘HIGHER GRADE’ ENERGY (THAT
CAN BE USED BY ORGANISMS) IS
CALLED (GIBBS) FREE ENERGY.
Section 7 suggests that it is possible to
consider ‘useful’ and ‘non-useful’ energy,
if we define the former as that which can
be transformed into other forms of energy,
and the latter as that which cannot.
total
energy
=
useful
energy
+
non-useful
energy
Physical scientists translate this into:
H
enthalpy
=
G
free energy
+
T x S
absolute
temperature
entropy
(T x S) is equivalent to non-useful energy, because it’s
proportional to the rate at which molecules move
about randomly – energy expended in making them do
this can’t be easily transformed into other forms of
energy.
13
9 THE CHANGE IN FREE ENERGY
DURING A PROCESS INDICATES
WHETHER THE PROCESS IS
SPONTANEOUS
(THAT
IS,
WHETHER IT OCCURS UNAIDED).
In a spontaneous process, a system:
(a) gives up energy
e.g. water runs downhill spontaneously,
giving up its potential energy;
and/or
(b) becomes more random (that is,
increases in entropy)
e.g.
complex
structures
decay
spontaneously,
giving up their potential energy.
14
So, according to the ‘translation’ outlined
in Section 8,
a spontaneous process involves
(a) a decrease in H;
and/or
(b) an increase in S.
And, because
H
=
G
+
TxS
(Section 8)
this means that any process leading to a
decrease in G (i.e. occurring with a -G)
is spontaneous.
This makes sense:
throughout the universe,
‘useful’ energy is gradually
(and spontaneously) being transformed
into less ‘useful’ heat
(as occurs during the flow of energy
through organisms) (Section 6).
15
10 THE CHANGE IN FREE ENERGY
DURING A REACTION IS RELATED
TO THE CONCENTRATIONS OF
THE REACTANTS RELATIVE TO
THEIR
CONCENTRATIONS
AT
EQUILIBRIUM.
A reaction
A
B
reaches equilibrium when the rate at which
A is being converted to B equals the rate at
which B is being converted into A.
Spontaneous reactions proceed towards
(but do not necessarily reach) equilibrium.
Suppose, for the reaction above,
equilibrium occurs when
there is 1 molecule of A for every 10
molecules of B.
16
What happens if the A to B ratio isn’t
1 to 10?
We can imagine various scenarios:
Molecular
ratio of
A to B
Status of
A
B
conversion
Status of
B
A
conversion
5 to 10
spontaneous
-G
non-spontaneous
+G
1 to 100
non-spontaneous
+G
spontaneous
-G
1 to 10
reaction at equilibrium
G = 0
To summarise:
the sign of G indicates on which side of the
equilibrium the reactant concentrations lie
at any particular time.
The size of G is an indication of how far
from the equilibrium the reaction is.
17
11 IN LIFE, SPONTANEOUS REACTIONS
ARE NOT ALLOWED TO REACH
EQUILIBRIUM.
For a system at equilibrium,
G = 0, (Section 10)
and no net energy flow occurs from one
process to another, so no work can be done.
Such a situation is incompatible with life.
Life involves continuous energy flow from
the environment, through the organism, and
back to the environment (Sections 4, 6).
For the flow to continue, the components of
the flow system must be stopped from
reaching equilibrium.
How is this achieved?
The energy flow occurs through pathways of
reactions (Section 14):
food
molecule
excretory
product
18
As the product of a reaction is formed, it is
removed by the following reaction, and so
the system is prevented from reaching
equilibrium.
So, as long as food is supplied and excretory
products are removed,
a steady, continuous flow occurs.
This system is said to be in a ‘dynamic
steady state’.
While the flow continues, the organism
‘saves’ free energy released during the flow,
to use in building its structure and in its
various activities (Sections 4, 6).
When the flow stops, the organism decays to
a non-organised collection of simple
molecules.
At that stage, it has reached equilibrium
with its environment.
19
BI25M1
ENERGY
TRANSFORMATIONS
LECTURE 2
AIMS:
To review:
life as a process depending upon
maintenance of dynamic steady states;
metabolism as a continuous flow of energy
through an organism;
roles of ATP-ADP inter-conversions in
metabolism.
[Lehninger (Edition 4)
Lehninger (Edition 5)
Instant Notes
pp.21-27 and Chapter 13
pp.19-26 and Chapter 13
Section C2]
20
12
A RECAP: LIFE
MAINTENANCE OF
STEADY STATES.
INVOLVES
DYNAMIC
Life involves systems of reactions held in
dynamic steady states and prevented from
reaching equilibrium (Section 11).
With the simple system
food
molecule
intermediate
molecule
a
excretory
molecule
b
(where a and b are the rates of the processes shown),
when a = b,
the system is in a dynamic steady state,
and the intermediate molecule,
although it is continuously being made and
degraded,
does not change in concentration.
21
In general,
compositions of cells and organisms as a
whole stay fairly constant over long
periods,
because of the maintenance of dynamic
steady states.
Thus,
haemoglobin molecules in red blood cells;
skin cells;
the body structure of mature organisms
and so on
are all maintained in relatively constant
compositions over long periods.
All are in dynamic steady states: none are
‘at equilibrium’.
Biologists refer to this state of affairs as
‘homeostasis’,
and biochemists refer to the balanced
synthesis and degradation of molecules as
their ‘turn-over’.
22
Flow rates (a and b) may be very different
in different parts of the flow system,
i.e. different molecules and cells may
‘turn-over’ at very different rates.
Flow rates may change in a controlled way
in response to changes in the environment
of the organism.
Thus, a system may change from one
dynamic steady state to another (with
faster, or slower flow through the system).
Such changes are discussed
Metabolic Regulation lectures.
in
the
23
13 ‘Metabolism’ is the continuous flow of
energy through the organism.
Another definition:
Metabolism is ‘the sum of all the chemical
transformations taking place in a cell or organism’
(Lehninger Edition 4 p.482; Edition 5 p.486).
During the flow of energy through
organisms (Section 6)
two types of process occur:
complex
‘food
molecules’
simple
molecules
used for
biosynthesis
simple
molecules
used for
biosynthesis
very
simple
excretory
molecules
energy
‘lost’ as heat
‘saved’
energy
used in
various
activities
‘saved’
used in
energy
various
activities
‘lost’ as heat
simpler
molecules
‘saved’
used in
energy various
activities
‘lost’ as heat
complex
molecules
‘lost’ as heat
complex
molecules
24
The processes are either
degradative;
occur with a -G
(i.e. free energy flows from an ‘exergonic’
process);
are spontaneous;
and are referred to as catabolic processes;
or
synthetic;
occur (in isolation) with a +G
(i.e. in order to occur, free energy must
flow to an ‘endergonic’ process);
are (in isolation) non-spontaneous;
and are referred to as anabolic processes.
The diagram shows that the latter
processes do not, in fact, occur in isolation:
free energy flows from the former
processes to the latter processes allowing
them to occur.
How energy flows from catabolic to
anabolic processes is discussed in Sections
19 and 21.
25
14 METABOLISM OCCURS THROUGH
PATHWAYS OF REACTIONS.
A particular part of the metabolic system
can be used to illustrate this statement.
Glucose, a molecule of high potential
energy, is used as a food material by many
organisms.
In the laboratory, it can be degraded by
heating it in air. The potential energy of the
glucose is released as heat:
glucose + 6O2
6CO2 + 6 H2O
high
potential energy
low
potential energy
heat
In cells, the same (overall) reaction occurs,
but through a series of small, cumulative,
chemical changes (an example of the
metabolic pathways referred to in Section
11).
We see later (Section 18) why such an
arrangement is advantageous to cells.
26
15 EACH STEP IN A METABOLIC
PATHWAY IS CATALYSED BY AN
ENZYME.
Spontaneous reactions move towards
(but, in organisms, do not reach)
equilibrium (Section 10).
‘Spontaneous’ does not mean ‘instantaneous’.
If it did, organisms,
with their complex structures of high
potential energy,
would instantly decay to simpler
structures with zero potential energy.
In time, of course, this decay DOES occur,
but it is not instantaneous.
The key function of enzymes is to increase
selectively the rate of particular
spontaneous reactions, allowing the flow
through particular metabolic pathways at
the rate required.
In the Enzymes lectures, we see
what it is that ‘holds back’ spontaneous reactions,
and how enzymes overcome this barrier.
27
16 CATABOLISM INVOLVES MOLECULAR
CONVERGENCE;
ANABOLISM INVOLVES MOLECULAR
DIVERGENCE.
CATABOLISM
ANABOLISM
proteins
20 amino acids
carbohydrates
a few sugars
a few, simple
intermediary
metabolites
a few fatty acids
lipids
8 nucleotides
nucleic acids
large number
of complex
molecules
large number
of complex
molecules
28
17 METABOLISM PIVOTS AROUND
INTERMEDIARY METABOLITES.
‘Metabolites’ are reactants of reactions
involved in metabolic flow.
‘Intermediary metabolites’ is the name
given to a small number of relatively
simple molecules, common to many
organisms, through which much of the
flow is channelled.
Thus another version of the flow through
the organism can be represented thus:
food
molecules
intermediary
metabolites
excretory
molecules
complex
molecules
An intermediary metabolite, then, tends to
be a component of several metabolic
pathways.
Examples are:
glucose 6-phosphate
pyruvate
acetyl coenzyme A (acetyl CoA).
29
18 ORGANISATION OF METABOLISM
INTO PATHWAYS ALLOWS FREE
ENERGY
FLOW
BETWEEN
CATABOLIC
AND
ANABOLIC
PROCESSES.
In the laboratory, glucose can be degraded
by heating it in air. Its potential energy is
transformed into heat. (Section 14)
glucose + 6O2
6CO2 + 6 H20
high
potential energy
zero
potential energy
heat
In the cell, the same (overall) reaction
occurs, but through a series of small,
cumulative chemical changes – a catabolic
pathway.
This allows some of the potential energy of
the glucose to be saved at particular
point(s) along the pathway.
30
Similarly, organisation of anabolic
processes as pathways allows free energy
to be ‘fed’ in at particular point(s) along
the pathways.
Free energy flowing from catabolic
processes enables the various activities of
the organism. Some of it flows to anabolic
processes.
CATABOLISM
complex
molecule
(like glucose)
simple
molecules
(like CO2
+ H2O)
free energy
some heat lost
throughout
the pathway
various activities
(e.g. locomotion)
complex
molecule
simple
molecules
ANABOLISM
This allows ‘coupling’ of exergonic
catabolism to endergonic anabolism.
(Section 13)
31
19
MUCH FREE ENERGY FLOW
BETWEEN PATHWAYS INVOLVES
ATP-ADP INTER-CONVERSION.
The structure of ATP
(adenosine 5’-triphosphate)
is in Lehninger Editions 4, 5 p.23
and Instant Notes p.94.
32
ATP and ADP are inter-converted by
hydrolysis and condensation.
hydrolysis
ATP
+
H2O
ADP
condensation
+
Pi
(inorganic
phosphate)
Because ATP has a higher potential energy
than ADP/Pi, hydrolysis occurs with a
decrease in free energy
(i.e. is exergonic):
G = - 7.3 kcal/mol
(or - 30.5 kJ/mol)
under ‘standard’ laboratory conditions
(pH 7; molar concentrations of ATP, ADP, Pi).
The condensation reaction requires a
corresponding input of free energy
(i.e. is endergonic):
G = + 7.3 kcal/mol
(or + 30.5 kJ/mol)
(under ‘standard’ conditions).
33
ATP hydrolysis to ADP + Pi is exergonic
because:
(1) hydrolysis relieves electrostatic repulsion
between the four negative charges that occur
in ATP in water at neutral pH ;
(2) more resonance is possible for ADP + Pi than
for ATP;
(3) more H-bonding with water is possible for
ADP + Pi than for ATP;
(4) ADP, when formed from ATP, releases H+ into
a medium of low [H+].
This combination of factors means that,
at the equilibrium of the inter-conversion,
[ADP and Pi] is high and [ATP] low.
In cells, [ADP] is lower, and [ATP] higher
than at equilibrium,
so movement towards equilibrium occurs
in the direction of hydrolysis,
which is therefore spontaneous, occurring
with a -G.
34
All of this is relevant to metabolism,
because free energy flowing from an
exergonic, catabolic pathway can be
‘saved’ by endergonic conversion of ADP
to ATP at particular reaction(s) of the
pathway.
And free energy flowing to an endergonic,
anabolic pathway can be ‘supplied’ by
exergonic conversion of ATP to ADP at
particular reaction(s) of the pathway.
So, modifying the Section 18 diagram:
complex
molecule
simple
molecules
ADP
ATP
some heat lost
throughout the pathway
ATP conversion to ADP may then be used
to drive various free energy-requiring
activities of the organism. Among them are
endergonic anabolic processes:
ADP
complex
molecule
ATP
simple
molecules
35
BI25M1
ENERGY
TRANSFORMATIONS
LECTURE 3
AIMS: To review:
examples of ATP-ADP inter-conversion in
free energy transfer during metabolism
roles of redox reactions in free energy
transfer during metabolism;
the difference between substrate-level and
oxidative phosphorylations.
[Lehninger (Edition 4)
Lehninger (Edition 5)
Instant Notes
pp.21-27 and Chapter 13
pp.19-26 and Chapter 13
Section C2]
36
20 ATP-ADP INTER-CONVERSION IN
METABOLISM
OCCURS
BY
PHOSPHATE TRANSFER, NOT BY
HYDROLYSIS/CONDENSATION.
To illustrate this, we can return to the
catabolic pathway by which the food
molecule glucose releases its potential
energy when degraded (Section 14).
One of the pathway steps involves
conversion
of
one
metabolite,
phosphoenolpyruvate (PEP), to another,
pyruvate.
And, at this step, some of the glucose
potential energy is ‘saved’ as ATP is made
from ADP.
glucose
PEP
ADP
pyruvate
ATP
37
How does converting PEP to pyruvate allow
endergonic conversion of ADP to ATP?
In the laboratory, PEP can be hydrolysed
to pyruvate and inorganic phosphate (Pi).
PEP
+
H2O
pyruvate +
Pi
The reaction is exergonic,
with a G of -61.9 kJ/mol
under ‘standard’ conditions.
We know (Section 19) that
ADP
+
Pi
ATP
+
H2O
is endergonic,
with a G of +30.5 kJ/mol
under ‘standard’ conditions.
In the cell, remember, the reaction that
actually occurs is
PEP
+
ADP
pyruvate +
ATP
38
This is equivalent to the sum of the two
laboratory reactions
PEP
ADP
+
+
H2O
Pi
pyruvate +
ATP
+
Pi
H2O
PEP
+
ADP
pyruvate +
ATP
Because free energy changes are additive,
the reaction occurring in the cell has a G
= to the sum of the Gs of the two,
separate, laboratory reactions
= (-61.9 +30.5)
= -31.4 kJ/mol
(under ‘standard’ conditions).
So, some potential energy of PEP,
(originally part of the potential energy of
glucose),
is ‘released’ as it is converted to pyruvate,
and ‘saved’ as the potential energy of ATP.
Notice that ATP synthesis did not involve
the actual condensation of ADP and Pi,
but the transfer of a phosphate group from
PEP to ADP.
39
A second illustration of phosphate group
transfer in metabolic energy flow is the
synthesis of an amino acid, glutamine,
from another amino acid, glutamate.
The process is endergonic, and ATP
conversion to ADP ‘supplies’ the necessary
free energy.
How does converting ATP to ADP allow
endergonic synthesis of glutamine?
In the cell, glutamine is made like this:
glutamate + ATP
glutamyl phosphate +
ADP
NH4+
glutamine
+
Pi
glutamine
+ ADP +
Pi
+ glutamyl phosphate
The net effect is
glutamate + ATP + NH4+
40
In the laboratory, glutamine synthesis like this
glutamate + NH4+
glutamine + H2O
is endergonic,
with a G of +14.2 kJ/mol
under ‘standard’ conditions.
And we know (Section 19) that
ATP
+ H 2O
ADP
+ Pi
is exergonic,
with a G of -30.5 kJ/mol
under ‘standard’ conditions.
In the cell, remember, the net effect of the
reaction that actually occurs is
glutamate + ATP + NH4+
glutamine
+ ADP +
Pi
This is equivalent to the sum of the two
laboratory reactions
glutamate + NH4+
glutamine + H2O
ATP
ADP
+ H 2O
glutamate + ATP + NH4
+
glutamine
+ Pi
+
ADP +
Pi
41
Because free energy changes are additive,
the reaction occurring in the cell has a G
= to the sum of the Gs of the two,
separate, laboratory reactions
= (+14.2 -30.5)
= -16.3 kJ/mol
(under ‘standard’ conditions),
So, potential energy of ATP,
‘released’ as it is converted to ADP,
is ‘supplied’ to the process of glutamine
synthesis.
Notice that this use of ATP did not involve
its actual hydrolysis to ADP and Pi,
but the transfer of a phosphate group from
ATP to glutamate.
Energy flow between many metabolic
pathways involves similar ATP-ADP interconversions through phosphate group
transfers.
Because of its role in transferring energy
between cellular processes, ATP is often
called the ‘energy currency’ of the cell.
42
21 FREE ENERGY FLOW BETWEEN
PATHWAYS
ALSO
INVOLVES
REDUCTION-OXIDATION (REDOX)
REACTIONS.
Much of the potential energy of food
molecules arises because they contain large
numbers of H atoms.
Examples are glucose
C6H12O6
and fatty acids, like palmitate
CH3(CH2)14COO-
The latter, in particular, resemble longchain hydrocarbons of petroleum, that are
also, in a different context, fuels.
Why should having H atoms give such
molecules potential energy, and how is this
relevant to energy transfer in metabolism?
43
H atoms may be said to have ‘high-energy
electrons’.
They are so-called
electropositive.
because
H
is
Electrons of electropositive atoms are
attracted to electronegative atoms. When
they associate with an electronegative
atom, a more stable state is reached, and
energy is released.
O atoms are very electronegative.
If the electrons of the food molecule H
atoms are made to combine with O to
produce water, much energy is released.
(Just as petroleum hydrocarbons, burned
in air, release energy.)
To summarise:
we ‘burn’ food molecules using oxygen we
breathe in, and ‘save’ some of energy
released. using inspired oxygen.
44
How does this work in practise?
In certain reactions of catabolic pathways,
H atoms are stripped, two at a time, from
what was originally a food molecule.
They are accepted by one of a small set of
co-reactants (represented as ‘X’), in a
redox reaction (making ‘XH2’).
reduced food molecule
oxidised product
X
XH2
‘XH2’ passes the H atoms, with their ‘highenergy’ electrons, through various redox
reactants, until eventually they reach
electronegative oxygen.
When they do, much energy is released.
Some is used to make ATP from ADP, and
so ‘saved’ by the organism.
45
What has this got to do with ‘free energy
flow between pathways’?
In some cases, XH2, instead of passing its
H’s towards O2, links the catabolic
pathway in which it was produced to a
particular reaction of an anabolic
pathway:
catabolic pathway
reduced food molecule
oxidised product
X
XH2
reduced product
oxidised starting material
anabolic pathway
To summarise again:
free energy flow between exergonic
catabolism and endergonic anabolism
occurs not just through ADP/ATP interconversion (Section 19),
but also
by inter-conversion of redox co-reactants
(‘X’/‘XH2’).
46
22 THE MAJOR REDOX CO-REACTANTS
(‘X’/XH2’) OF METABOLIC PATHWAYS
ARE NAD, NADP and FAD.
.
All are dinucleotides containing adenine
and ribose,
with structures similar in part to that of
ATP. (Section 19)
47
[NAD, NADP, FAD structures are also in
Lehninger Edition 4 pp.513,516; Edition 5
pp.517,520; Instant Notes p.89.]
To summarise:
2 hydrogen atoms
(i.e. 2 protons, 2 electrons)
X
XH2
NAD+
NADP+
FAD
NADH + H+
NADPH + H+
FADH2
Passing H’s towards O2 (Section 21)
mainly involves NAD and FAD,
while NADP is mainly involved in energy
flow between catabolism and anabolism.
(Section 21)
48
23 ATP SYNTHESIS FROM ADP
OCCURS BY SUBSTRATE-LEVEL OR
OXIDATIVE PHOSPHORYLATION.
Substrate-level phosphorylation is ATP
synthesis that occurs without direct
intervention of redox reactions.
Oxidative phosphorylation is ATP synthesis
that occurs as a consequence of oxidation
of a co-reactant (‘XH2’).
To illustrate this, we can return to the
catabolic pathway by which the food
molecule glucose releases its potential
energy when degraded (Sections 14,18,20).
Partial breakdown of glucose, to lactate or
ethanol, releases a little of its potential
energy, and some is saved by making ATP
(Sections 19,20).
glucose
lactate
or ethanol
ADP
ATP
49
No redox reactions are (directly) involved.
This is substrate-level phosphorylation.
Complete breakdown of glucose to CO2
and H2O involves production of reduced
co-reactants (XH2), which eventually pass
on ‘high energy electrons’ to O2 (Section
22). All the potential energy of glucose is
released, and much more ATP is made.
This is oxidative phosphorylation.
glucose
CO2
ADP ATP
X
XH2
substrate-level phosphorylation
YH2
Y
ADP
ATP oxidative phosphorylation
1
/2O2 H2O
The X-XH2/YH2-Y redox reaction represents a
series of such reactions, through which H atoms
with their electrons pass before eventually reaching
O2. This series is called ‘the terminal respiratory
system’.
50
Only hexoses, like glucose, generate ATP
by substrate-level phosphorylation.
Other foods, like fatty acids (Section 21),
can only generate ATP by oxidative
phosphorylation.
Although it produces small amounts of
ATP,
substrate-level phosphorylation is not
trival:
it provides ATP for human cells lacking
oxygen (e.g. in vigorously exercising
skeletal muscle)
and/or lacking mitochondria (which is
where oxidative phosphorylation occurs)
(e.g. RBCs).
Because of this,
glucose is a major food for most
organisms,
many of which can also make it
(gluconeogenesis) from non-carbohydrate
sources.
51
The coming course deals with:
the following fundamental catabolism-associated processes:
glycolysis: the partial catabolism of hexoses to 3-carbon pyruvate,
with the conservation of a little of the potential energy of the hexose
in ATP formation (substrate-level phosphorylation);
the pyruvate dehydrogenase-catalysed reaction: in which further
catabolism of the 3-carbon pyruvate to 2-carbon acetyl CoA occurs;
the partial catabolism of fatty acids: this is ‘ oxidation’ and again
generates 2-carbon acetyl CoA;
the citric acid cycle: in which further catabolism of the 2-carbon
acetyl CoA to CO2 occurs;
the terminal respiratory system: in which electrons, originally part
of food molecules and subsequently passed during their catabolism
to redox co-reactants, are then passed through a series of redox
reactions to oxygen to form water, much of the potential energy of
the food molecule being conserved in ATP formation (oxidative
phosphorylation);
the pentose phosphate pathway: in which an alternative catabolism
of hexoses is used to produce other sugars and a particular form of
‘XH2’ (NADPH + H+);
52
and the following processes which centre on anabolism:
glycogen synthesis: the storage of hexose residues in polymeric form
which may be mobilised later (glycogen breakdown);
gluconeogenesis: in which glucose is synthesised from noncarbohydrate sources;
fatty acid synthesis: in which 2-carbon acetyl CoA molecules are
precursors of long hydrocarbon chains;
triacylglycerol and phospholipid synthesis: in which fatty acids are
used in the synthesis of molecules with important structural, storage
and other roles;
photosynthesis: in which sugars are synthesised from very simple
precursors, using sunlight to drive the process.
We will also consider:
nitrogen metabolism: the inter-conversions of nitrogen-containing
molecules, including their entry to and exit from the biosphere;
enzymes: the properties of the catalysts of the reaction steps of
metabolic pathways;
metabolic regulation: the ways in which flow rates through
pathways can be changed in the face of changing requirements of
the cell/organism.
53
We will concentrate on function rather than (just
for the sake of them) names and structures of the
chemical intermediates, although a coherent
discussion of function requires some knowledge of
names and structures.
And, in a metabolic retrospective, we will deliberately
pause to consolidate understanding of how the
pathways interact and connect.
The various pathways can seem daunting when first
encountered. In fact, there are relatively few major
ones, and they are common to very many organisms.
When you encounter a pathway for the first time, don’t
start by trying to remember every last detail of the
pathway. Begin by following the advice in Lehninger
(Editions 4,5 p.488):
Ask yourself
‘What does this chemical transformation do for the
organism?’
‘How does this pathway interconnect with the other
pathways … to produce the energy and products
required for cell maintenance and growth?’
If you reach an understanding of why evolution has
made the pathway the way it is, you will be able
more easily to remember its various features.