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BIOENERGETICS
Terminology
Before starting the formal presentation of bioenergetics, we need to dene some important terms.
Surroundings
System
Exchanges
of matter
and energy
Universe
Figure 2-2 The universe consists of the system(s) plus the surroundings. At any one time,
a reaction taking place in the system results in a
decrease in the energy (free energy) available to
do the work of the system. Consequently, over
the long term, an input of energy from the surroundings is required to maintain the system.
The energy content of the universe is always
constant.
21
Laws of Thermodynamics
15
Range of
muscle temperature
chanical energy. In biological systems, heat is released as an essential but useless component of
reactions in which other forms of work are accomplished. This is a fundamental difference between
biological and mechanical engines.
Another characteristic of biological systems is
their temperature dependence. Two factors merit
consideration here. First, biological systems are
sensitive to small increments in temperature. Above
45 C, and certainly above 60 C, tissue proteins become denatured, or degraded. Consequently, although a muscle might theoretically contract faster
at 50 C than at 35 C, increasing the temperature
that much would literally cook the muscle.
Second, the rates of biological or enzymatic reactions are also sensitive to temperature. Usually,
the effect of temperature on reaction rates is studied
by changing the temperature in multiples of 10 C.
The result of such a change is called a Q10 effect.
Increasing the temperature 10 C, for example, doubles the rate of an enzymatic reaction, and the Q10 is
2. Figure 2-3 illustrates the Q10 effect. In that gure,
note the large effect of temperature changes within
the normal range of muscle temperature.
Changes in temperature can be advantageous as
well as deleterious to individuals. For instance,
even though a lizard cannot capture heat to do cellular work, it can sit in the sun to warm itself, and in
this way it takes advantage of the Q10 effect. Some
rodents can adapt biochemically when they are exposed to extreme cold; these adaptations allow
them to consume extra oxygen and generate heat
without shivering, which would endanger their
survival. Also, many athletes have found that preliminary exercise (warming up) makes for better
performance. We shall see (in Chapter 21) that preliminary exercise has several benecial effects, one
of which is to warm up muscle, thus taking advantage of the local Q10 effect.
Excessively high as well as low temperatures
can be harmful. Although warming up can increase
the speed of particular enzymatic processes in muscles through the Q10 effect, temperatures of over
40 C have been observed to decrease the efciency
of oxygen use in muscle. This can negatively affect
endurance. It has also been noted that cooling brain
10
10
20
30
Temperature ( C)
40
50
Laws of Thermodynamics
Repeated observations of events in the physical
world reveal that two fundamental principles, or
laws, always hold. The rst law of thermodynamics
states that energy can be neither created nor destroyed. Whenever there is an exchange of energy or
matter between a system and its surroundings, the
22
BIOENERGETICS
total energy content in the universe remains constant. The expression We get a burst of energy is
not quite correct. Rather, humans consume food
(parcels of chemical energy) and degrade the foodstuffs, converting some of the chemical energy to
heat and cell work, and releasing the remaining
chemical energy unused in body excrements.
Equation 2-1, which describes weight loss or
gain in healthy human bodies, is not a statement of
the rst law but does conform to the rst law. According to this equation, the only way obese people
can lose fat is to eat less and exercise more. If the energy input (food) is less than that expended as work
and heat resulting from exercise, then the amount
stored (as fat) will be reduced.
Energy in Energy out Energy out Energy stored
1fat2
1heat2
1work2
1food2
(2-1)
In addition to telling us that energy is not created or destroyed, but rather interconverted among
forms, the rst law tells us to be careful to account
for all the energy.
The rst law of thermodynamics implies that
energy forms can be exchanged, but it does not tell
us in what direction the exchanges will occur. The
second law of thermodynamics tells us that processes always go in the direction of randomness, or
disorder. A quantitative measure of this disorder is
termed entropy. As the result of the second law, entropy always increases. In biology, the second law
tells us that whenever energy is exchanged, the
efciency of the exchange will be imperfect and
some energy will escapeusually in the form of
heatthus increasing entropy in the universe. Now
consider a system that is increasing in organization,
such as a child growing. Is this increasing organization of matter contrary to the second law? The answer is no. The process of growth requires a tremendous input of energy from the environment, and for
a little growtha little increase in ordera lot of
heat (random energy) is released. In general, when
one biological process moves some product toward
a higher level of organization, it is driven by at least
one linked or coupled entropic reaction.
There are many examples of concentrated units
of energy being dispersed into random energy
Enthalpy
Energy
of
activation
Potential energy
D
E1
(E is
negative)
E2
(E is
positive)
B
23
Progress of reaction
getics, the linkages between exergonic (energyyielding) and endergonic (energy-consuming) reactions is usually indirect. As we shall see in the
following sections, part of the energy available
from exergonic processes is captured in the form
of a high-energy intermediate compound, adenosine triphosphate (ATP). In a complementary way,
most endergonic reactions in mammalian systems
are catalyzed by an enzyme that uses the energy
of ATP.
Even though reaction ASB is downhill and
spontaneous, it is not likely to happen because an
energy barrier, called the energy of activation, must
rst be overcome. In other words, even though the
reaction ASB is classied as spontaneous, some energy has to be put in to activate the system and
prime the pump. As we shall see, several important biochemical pathways, such as the conversion
of glucose to glucose 6-phosphate in glycolysis
(Chapter 5), begin with such activating steps. We
will also see that enzymes are important because
they lower the energy of activation.
Although the energy of activation impedes
some processes, the world as we know it depends
on other processes having very high energies of activation. For example, oxides of nitrogen and other
automobile exhaust emissions are currently very
much in the news. Oxides of nitrogen are formed
(2-2)
N O2 S NO2
(2-3)
These are spontaneous reactions with high energies of activation. In the automobile combustion
chamber, extremes of temperature and pressure
activate the reaction and produce noxious products. Without very high energies of activation,
these reactions might well cause the atmosphere to
catch re.
In metabolic processes, initial reactants must
rst be activated. Because enzymes can lower the
energy of activation, there is enzymatic control over
these processes.
Enthalpy
In the example of a spontaneous reaction just cited
(ASB in Figure 2-4), we saw that energy was released (E1) because the energy content of the products was less than that of the reactants. More
specically,
g 1EA2 g 1EB2 E1
(2-4)
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BIOENERGETICS
Here, g means sum of or content of. Accordingly, g(EA) means the content of all the energy in A.
In natural events, however, it is difcult to determine the change in energy (E) because some
work is done in the atmosphere. Enthalpy (symbolized by H) takes into account this work done in the
atmosphere by adjusting E for changes in pressure
and volume.
H E PV
(2-5)
Fortunately, volume changes at constant pressures are extremely small, and for most biological
reactions, PV 0. Therefore,
E H
(2-6)
this energy is available, or free, to do work. In biological reactions, such as those involved in muscle
contraction, free energy changes are of primary
importance.
The following equations summarize what has
been covered so far:
Energy change Change in energy available
1enthalpy 2
to do work
Change in unavailable energy
(2-8)
(2-9)
(2-7)
Free Energy
Although the second law of thermodynamics states
that the entropy of the universe always increases,
and it is the drive toward the entropic condition
that allows physical and chemical reactions to occur, the random energy of entropy is not directly
useful in the performance of cell work. As implied
by the rst and second laws of thermodynamics,
there exists another component to the total energy
of a system. The term free energy is used because
(2-10)
(2-11)
where means change and T is absolute temperature. The temperature term is necessary to get entropy in appropriate units. Because of the second
law, and by convention, as any real process proceeds, the free energy carries a negative sign. Another way to remember that free energy (the useful component) carries a negative sign is to reason
that a negative free energy term means that energy
is given up by a reaction and is available to do
work. Typically, in working human muscle 25% of
the enthalpy change is available to do work and
75% appears as heat; rephrased, muscle efciency
during locomotion approximates 25%. Figure 2-5
summarizes the various components of chemical
energy.
E
(Energy change)
H
(Enthalpy)
PV
(work on the
atmosphere, usually ~ 0)
TS
(Entropy)
G
(Free energy)
b. A
c. A
K eq =
25
3 B4
3A 4
3products4
3reactants 4
(2-12)
G RT ln K eq
(2-13)
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BIOENERGETICS
TABLE 2-1
Keq
G
(kcal mol 1)
0.001
0.010
0.100
1.000
10.000
100.000
1000.000
4.09
2.73
1.36
0.00
1.36
2.73
4.09
Endergonic reactions
Exergonic reactions
(2-14)
K eq
3 P4 p 3Q4 q
3 R4 r 3S4 s
(2-15)
For the same reaction in a living cell, a determination of the actual, not equilibrium, concentrations
gives the mass action ratio (MAR):
MAR
Here we can clearly see what the effect of concentration change is on the actual free energy
change of a reaction. Also, we can see that temperature has a direct effect on the free energy change.
Although it is not directly shown, a change in
pH would also affect the actual free energy. Some
things to consider are the effects of exercise on
muscle metabolite concentrations, pH, and temperature. These factors can affect exercise performance.
3 P4 p 3 Q4 q
3 R4 r 3 S4 s
(2-16)
G G RT ln MAR
(2-17)
The mechanisms of energy conversion are contained within each cell; therefore, cells require the
presence of a substance that can receive energy input from energy-yielding reactions. Equally important, that substance must be able to yield energy to
reactions requiring an energy input. In our cells,
that substance is almost always adenosine triphosphate (ATP).
In Chapter 4, we will discuss in some detail
the processes of cell respiration and cell work. In the
cell, respiration represents the conversion of the
chemical energy of foodstuffs into useful chemical
form. Cell work represents the conversion of that
useful form to other forms of energy. In order to
function, this coupled system of energy-yielding
and energy-utilizing reactions depends on having a
substance that can act both as an energy receiver
and as an energy resource, or donor. In most cells of
most organisms, ATP is that substance. Because of
its central role in metabolism, ATP is frequently referred to as the common chemical intermediate. If
most species had not evolved to use ATP, they
would have evolved to use a related compound.
The history of the study of ATP is marked by
several notable discoveries. In the 1920s, the work of
Fletcher, Hopkins, and Hill led to the belief that the
release of lactic acid in muscles was the stimulus for
contraction. Subsequently, after Embden showed
that rapid freezing of small isolated muscles after a
contraction prevented the formation of lactic acid, it
was concluded that lactate was not the cause of contraction. In the early 1930s, Lundsgaard showed
27
Creatine DNFB
ADP CP S
kinase 1reaction blocked2
(2-19)
NH2
N5
4
HC
P~ O
P~ O
6 1C
3 2
Adenine
8 CH
CH2
4C
H 3 C
OH
D-ribose
H C 1
2
C H
OH
Adenosine
Adenosine monophosphate (AMP)
Adenosine diphosphate (ADP)
Adenosine triphosphate (ATP)
Creatine
ADP CP S ATP C
(2-18)
kinase
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BIOENERGETICS
10
G (kcal)
4.0
5.0
6.0
7.0
8.0
9.0
pH
Figure 2-8
the terminal phosphate results in adenosine diphosphate (ADP); cleaving two phosphates gives adenosine monophosphate (AMP). With no phosphates,
the compound is simply the nucleotide, adenosine.
In the cell, ATP is negatively charged, and the terminal phosphates of each ATP molecule often associate with a magnesium (Mg2). The Mg2 is usually
required for enzymatic activity.
The reactions in which ATP is split to ADP to
liberate energy involve water. Accordingly these
reactions are called hydrolyses, meaning split by
water.
ATPase
(2-20)
enzyme
Summary
Phosphoenolpyruvate
14.0
1,3Diphosphoglycerate
G Hydrolysis (kcal)
12.0
10.0
~P
~P
High-energy
phosphate compounds
Phosphocreatine
~P
29
8.0
ATP
6.0
~P
~P
4.0
2.0
Low-energy
phosphate compounds
Glucose
6-phosphate
Glycerol
3-phosphate
SUMMARY
Performance in muscular activity depends on energetics. The utilization of energy by machines, both
mechanical and biological, can be precisely dened.
Basically, two considerations govern physical and
biological reactions involving energy exchanges:
(1) Energy is not created but is acquired in one form
and converted to another; and (2) the interconversion of energy among forms is inefcient, and a
large fraction of the energy released appears in an
unusable form, usually heat. In the cell, the transduction of chemical energy to other forms of energy
depends on the metabolism of adenosine triphosphate (ATP). Elaborate enzymatic pathways exist to
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BIOENERGETICS
SELECTED READINGS
Bray, H. G., and K. White. Kinetics and Thermodynamics
in Biochemistry. New York: Academic Press, 1966.
Cain, D. F., and R. E. Davies. Breakdown of adenosine
triphosphate during a single contraction of working
muscle. Biochem. Biophys. Res. Com. 8: 361366, 1962.
Gaesser, G. A., and G. A. Brooks. Muscular efciency
during steady-rate exercise. J. Appl. Physiol. 38: 1132
1139, 1975.
Gibbs, C. L., and W. R. Gibson. Energy production of rat
soleus muscle. Am. J. Physiol. 223: 864 871, 1972.
Helmholtz, H. ber die Erhaltung der Kraft, Berlin (1847).
Reprinted in Ostwalds Klassiker, no. 1, Leipzig, 1902.
Hill, T. L. Free Energy Transductions in Biology. New
York: Academic Press, 1977.
Kleiber, M. The Fire of Life. New York: Wiley, 1961,
pp. 105 124.
Krebs, H. A., and H. L. Kornberg. Energy Transformations
in Living Matter. Berlin: Springer-Verlag OHG, 1957.
Kushmerick, M. J., and K. E. Conley. Skeletal muscle
energetics and exercise tolerance. Biochem. Soc. Trans.
30: 227231, 2002.