Energy
The meaning of “energy” in energy
metabolism
In a haste to learn the individual reactions in a pathway, its
easy to lose sight of the purpose of the pathway. With energy
metabolism, the purpose is to generate energy, generally as ATP or
NADH or some high energy compound that will be used in a later
anabolic step. Glycolysis and Krebs cycle reactions have a high
number of kinase and dehydrogenase enzymes, respectively, for this
reason. This class of enzymes is intimately connected with energy
production and conservation. Pathways in the cytosol tend to be less
energy yielding, whereas those in the mitochondria are almost totally
devoted to energy production. This tutorial will bring you closer to
understanding why and how cells conserve energy. It will also help
you see the logic behind molecular energy calculations. As you listen
to your heart pump or move your arm to scratch your head, you
should be able to tell what purpose energy serves to life.
What is energy conservation?
The terms energy conservation and energy generation tend to carry the
same meaning. Conservation implies “avoiding heat”, or channeling the energy
differential between reactants and products into the synthesis of a compound.
Because energy as heat cannot be exploited in an isothermal system, biological
systems have to conserve energy by biosynthesis. Suppose for example ATP is
hydrolyzed during a reaction (click 1). The standard energy differential between
reactants and products (Go’) of that reaction is 30.5 kJ/mol.
ATP + H2O
ADP + PO4
This means the environment of the cell gains 30.5 kJ of heat energy for each
mole of ATP hydrolyzed by water. Obviously, this is wasteful. To counter the
loss, ATP hydrolysis is coupled with the synthesis of a phosphorylated
compound. You saw this as a “coupled” reaction when ATP was needed to
produce glucose-6-PO4 or fructose 1,6-bisPO4 (click 1).
Glucose + ATP
Fructose-6-PO4 + ATP
Glucose-6-PO4 + ADP
Fructose 1,6-bisPO4 + ADP
Now you see that by making glucose-6-PO4 or fructose 1,6-bisPO4, the cell avoids
losing the larger part of the ATP hydrolysis energy as heat. This is energy
conservation. Click one to go on.
Direct vs Indirect Energy Production
The energy generated in metabolic pathways comes in two forms,
direct or indirect. Direct or “substrate level” refers to energy generated during
a particular reaction. The production of ATP by reacting ADP with PEP is an
example of this type (click 1)
COO
COO
C~OPO3= + ADP
C=O
CH2
CH3
+ ATP
Indirect refers to energy channeled into a compound that will return
the energy at a later step. High energy compounds such as acyl-phosphates
or thioesters fit this example. Another is NADH generated during oxidation
reactions in the cytosol or Krebs cycle. When L-malate is oxidzed by NAD+,
NADH is generated (click 1). NADH and FADH2 have trapped the electron
pair from the oxidation in their structures and will release the energy when
they themselves are oxidized.
COO
COO
:
C=O
HO-C-H
+
+ NAD
+ NADH + H+
:
CH2
CH2
COO
COO
Calculating energy yield in glycolysis
Calculating energy yield helps you see the energy phase of metabolism
in real numbers. Take for example the energy yield when glyceraldehyde-3-PO4
is oxidized to pyruvate. How much energy is conserved in this reaction? To
determine that number we need to know the pathway. We also need to know if
anaerobic or aerobic conditions prevail. First the pathway. There are 5 enzymecatalyzed reactions to consider (click 1).
glyceraldehyde-3-PO4 + PO4 + NAD+
1,3-bisPO4 glycerate + ADP
3-phosphglycerate
2-phosphoglycerate
PEP + ADP
glyceraldehyde-3-PO4 + PO4 + NAD+ + 2ADP
1,3-bisPO4 glycerate + NADH + H+
3-phosphoglycerate + ATP
2-phosphoglycerate
PEP + H2O
pyruvate + ATP + H2O
pyruvate + NADH + H+ + 2ATP + 2H2O
Removing the common terms on both sides yields a final equation (click 1).
We see that the phosphate on glyceraldehyde-3-PO4 and the inorganic PO4
both contribute to formation of ATP. Thus, 2 ATPs are formed by the 5
reactions. Under anaerobic conditions “two” represents the final yield. But, if
the reaction was carried out with oxygen and involved the mitochondria,
energy to the equivalent of 5 ATPs would result. Click 1 to see why.
Energy yield in the mitochondria
The mitochondria is the heart of aerobic metabolism. Electrons in
NADH and FADH2 are channeled into the electron transport system, which is
driven by O2. A large part of energy of oxidation of the electron transport
components is preserved in ATP. Each NADH generates the equivalent of 3
ATPs and each FADH2, 2 ATPs for each pair of electrons transferred to oxygen
(click 1).
O2
NADH
:
Electron transport
H2O
NAD
ATP
ATP
ATP
NADH from the cytosol yields its electrons indirectly via a shuttle. NADH
generated by the 3 NAD-linked dehydrogenases in the Krebs cycle provide
most of the energy. For example, each citrate molecule oxidized to CO2 and
H2O generates the equivalent of 36 ATPs. Click 1 to see how this value was
obtained.
Energy yield in the Krebs cycle
A cycle implies the last intermediate returns to the front. Each turn of the
Krebs cycle results in the loss of 2 carbons as CO2 and generates 3NADH, one
FADH2 and one GTP (click 1). A 2-carbon compound, such as the acetate group
on acetyl-CoA, therefore, yields 12 ATPs of energy.
Acetyl-CoA
citrate
oxaloacetate
isocitrate
CO2
NADH
NADH
-ketoglutarate
malate
NADH
fumarate
CO2
succinyl-CoA
FADH2
GTP
succinate
C4H4O5 + 31/2 O2
C6H8O7 + 41/2O2
C4H6O5 + 5 O2
4CO2 + 2H2O
6CO2 + 4H2O
4CO2 + 3H2O
Now, suppose instead of acetylCoA we want to determine the ATP yield
when oxaloacetate (OAA) is oxidized (click
1). First write the equation for the oxidation
(click 1). OAA yields 4 moles of CO2 for each
mole oxidized. Thus, 2 turns of the cycle are
needed to oxidize all of the carbons in OAA to
CO2. Two turns is equivalent to 24 ATPs.
Performing the same analysis for
citrate shows 6CO2 liberated, or 3 turns of the
cycle (click 1). Thus, citrate yield 36 ATPs, or
one third more energy than OAA. Finally lets
consider the oxidation of malate (click 1).
Malate has 4 carbons, which means the
oxidation will generate 4CO2. But, we also
need to oxidize malate to OAA, which
generates one NADH. Thus 3 more ATPs
than OAA, i.e., 24 + 3= 27 ATPs. Click 1 to
test and expand your understanding.
Test and Expand your understanding about energy
1. How many phosphorylated intermediates are in the Krebs cycle?
Ans: None. GTP is synthesized from GDP + Pi. GTP, however, is not a cycle
intermediate.
2. How is ATP generated in the Krebs cycle?
Ans: Indirectly. The reduced coenzymes, NADH and FADH2 shuttle electrons to the
electron transport system and energy is preserved by ATP synthesis
3. Is pyruvate → acetyl-CoA the only way to enter carbons into the Krebs cycle?
Ans: No. Any compound that can be converted into a Krebs cycle intermediate will
contribute carbons to the Krebs cycle. This applies to aspartate and glutamate,
which form OAA and -ketoglutarate, respectively.
4. What numbers should I remember in order to calculate energy yield in the
Krebs cycle?
Ans: In terms of ATP, remember that each NADH is equivalent to 3, each FADH2 to 2,
and each turn of the cycle 12 ATPs.
5. How many ATPs are generated when succinyl-CoA is oxidized in the cycle?
Ans: 30. One for GTP, two for FADH2 and 3 for NADH must be added to the 24 for 2
turns of the cycle.