The World Turned Upside Down: The Second Low-Carbohydrate Revolution (27 page)

When we write A
⎯➛
B, we want to know whether the reaction will proceed from right to left
spontaneously?
"
Spontaneously
"
means without
the addition of energy.
It does not mean fast, which is a separate question. The 4 kcal of
energy that
you measure in the calorimeter is both a measure of the tendency of the
reaction to occur (oxidations generally produce energy) and also the
maximum
energy available to do work. They are very closely related because,
although
living systems do mechanical (muscle) work, the main use of the energy
is in
chemical work, synthesizing metabolites and cell material.

The second law leads to the
definition of a number of
different forms of the energy (which are used under different
conditions). The
particular form of the energy that is used under conditions of constant
temperature and pressure (where biochemists usually work) is called the
Gibbs
Free Energy, almost always abbreviated with the letter G, and the
change
associated with chemical or other processes is written with the Greek
delta,
ΔG. The Gibbs Free Energy for a chemical is precisely defined as the
maximum work you can get from running the reaction at constant
temperature and
pressure and it is identified with the tendency of the reaction to go
in the
forward direction. The 4 kcal produced by the oxidation of glucose
tells you
that is the most you could get out of it in terms of work or
driving other
chemical reactions. In practice, some may be wasted as heat or other
unproductive processes.

real thermodynamics.

You can gain some insight by going
back to the beginning. A
fundamental idea is notion of system and environment. In fact, chemical
thermodynamics tends to focus only on the system (the chemical
reaction).
Otherwise all food would have zero calories because when you measure
combustion
in the calorimeter (where calories are determined), the heat lost by
combustion
of the food would be equal to the heat gained by the calorimeter, so
from
direct application of conservation of energy, there are no calories to
assign
to the food. Chemical thermodynamics emphasizes the reaction of the
system, not
the whole universe. We want to know about the energy exchange when we
burn
food. The complete oxidation of glucose in the calorimeter
produces
4 kcal. It is not about conservation. It is about dissipation of
energy.

The word thermodynamics is thrown
around a lot in nutrition,
mostly by people who have no idea what it is about. Again, you don't
need
thermodynamics to do nutrition but if you do it, you have to do it
right so, in
case you want to see what people really do in chemical
thermodynamics, I
will present a good example.

The basic idea is that we identify
the energy of a chemical
reaction with spontaneity, that is, whether the reaction goes forward
by itself
or whether you have to do something to make it go. (Again, spontaneous
does not
mean fast but only that no energy has to be added to make things go).
The rule
is that if the Free Energy change is negative (ΔG < 0) for the
reaction, the reaction is downhill and will go by itself and will give
off
energy (which you may be able to capture by coupling it to another
chemical
reaction or to some kind of mechanical, electrical or heat machine).
The Gibbs
Free Energy has two components, the heat of reaction, called the
enthalpy
(ΔH) and the entropy
(ΔS).

Figure
14-3
. Chemical energy can be
thought of as analogous to potential energy in physics. In the diagram,
the
boulder has potential energy by virtue of its height on the cliff. The
conversion of reactant to product is down-hill (
Δ
G
is (-)). Work can be done by pushing the boulder off the cliff. For the
reverse
reaction, you would have to do an amount of work equal to +
Δ
G to move the
boulder up the cliff.

Here's a simple example of what you
might do in real thermo.
Suppose that you wanted to know about the formation of carbon monoxide
(CO) and
how much energy is given off if carbon is oxidized to CO. Generally
thought of
in the context of a poison, CO has other uses and, among other things,
a small
amount is produced in the human body (during the breakdown of heme from
hemoglobin). So is the oxidation of carbon to CO uphill or downhill and
by how
much? To keep it simple, we'll take the heat of reaction, (ΔH). We can
do
the experiment so that the entropy is not an important player (low
temperature). The heat of reaction is easily measured.

In the case of oxidizing carbon,
then, if heat is given off
(ΔH = (-)) the reaction will be spontaneous and go by itself. The
problem
with trying to figure out how much energy you can get by burning carbon
to
carbon monoxide is that you can't really measure it. If you try to
carry out
the reaction, you always get some CO
₂
. So, what
can you do?.

Technically, the heat of reaction
(enthalpy), the entropy
and the Gibbs free energy, are what are called state functions. This
means that
they are independent of path. By analogy, they are like the absolute
distance,
the "as-the-crow-flies" mileage from New York to San Francisco. It does
not
depend on whether you fly direct or whether you are on the flights I
always
wind up with, going to Memphis and Denver and then San Francisco. In
thermodynamics, if we can find any path, the energy must be the same
for the
path that we want.

Here's how we do it: We want to
measure the heat of reaction
for oxidation of carbon to CO. We can't measure that directly. However,
we can
measure the enthalpy of burning of carbon to CO
₂
.
(A minus sign
means heat is given off).

C + O
₂
→
CO
₂
    
ΔH
= - 94 kcal

We also know the energy of
burning CO to CO
₂
.

CO + ½ O
₂
→ CO
₂
    ΔH =
- 68 kcal

Another great simplifying feature of
thermodynamics is that
the energy for going the other way is the same numerically with the
opposite
sign, so:

CO
₂
→ CO + ½ O
₂
    
ΔH
= + 68 kcal

State functions can be added just as
in simple algebra. The
associated energies add up too (
Figure
14-4
).

Figure
14-4
. Calculating heat of reaction for
formation of CO. Path of
the blue arrows (measured) must equal the direct conversion to CO, so
we just
add them up. (Note: energies in figure in kJ = 4.28 kcal).

The beauty of thermodynamics – the
attraction to those
people, like Einstein, who like it – is that you can manipulate the
results
with elementary algebra. The great simplicity in this kind of
calculation
reflects its highly predictive power. What did we do? We had two
different
paths from carbon to carbon monoxide, one (two-step) path that we could
calculate and one that we are trying to find out. They must be equal,
as in
Figure 14-4
.
The principle that allows you to add up
heats of reaction is called Hess's law.

Hess's law shows that
"a calorie is" not "a
calorie"

What follows is a Hess's law analysis
of "a calorie is
a calorie." In the context of nutrition, the law implies that energy
yield
for metabolism will be path-independent, that is, the same for all
diets and
proportional to the calorimeter values. The calorimeter values say that
energy
yield for carbohydrate and for protein are equivalent fuels, ΔG
(oxidation) = -4 kcal/mol as shown in Figure 14-5. Remember that a (-)
sign
means energy is given off and the process is spontaneous. The calories
in food,
again, is the energy for burning the food to CO
₂
and water. Here's
the plan. We make two paths for oxidizing protein: path 1 (direct) or
path 2 +
path 3 (first convert to carbohydrate).

Figure 14-5.
According to Hess
'
s
Law (adding up energies), the energy for path 1,
Δ
G1
should be equal to the energy for path 3 followed by path 2,
Δ
G1 -
Δ
G2.
Using calorimeter values and the principle that a calorie is a calorie
leads to
a contradiction.

In path 1, we burn protein directly
to CO
₂
. Now,
because free energy is a state variable, the free energy ΔG
₁
must be equal to the sum of ΔG
₂
, the energy for
path 2 plus
ΔG
₃
, the energy for path 3. This means that ΔG
₃
for path 3 must be about zero. However, this is the process of
gluconeogenesis.
Students work very hard learning that gluconeogenesis is an endergonic
process,
costs energy (about 6 ATP). Assuming that only the calories measured in
the
calorimeter are important leads to a contradiction.

The non-equilibrium
picture

One more level of sophistication. To
some extent, it is not
really about thermodynamics at all, or at least not equilibrium
thermodynamics.
Equilibrium thermodynamics is what is usually studied and we are taught
that
rates of reaction are considered separately from energy. The results of
equilibrium thermodynamics tell us that amino acids are more stable
than
proteins. The rate of breakdown, however, is very slow. If you could
keep the
bacteria off your steak it would last for months or years. At the end
of time
it would be all amino acids (or even simpler things). In biochemistry,
however,
rates become important because living systems are not at equilibrium
until they
die.  Things are moving forward. All the reactions in biology
are catalyzed by
enzymes which control the
speed
of a reaction, not the energetics. A better way to put it might be to
say that
the key players in all this are hormones and hormones generally affect
enzymes
which, in turn, affect rates, not energy.