Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

60 Chapter 2: Cell Chemistry and Bioenergetics
as rapidly as they do through water. A small organic molecule, for example, takes
only about one-fifth of a second on average to diffuse a distance of 10 μm. Diffusion
is therefore an efficient way for small molecules to move the limited distances
in the cell (a typical animal cell is 15 μm in diameter).
Since enzymes move more slowly than substrates in cells, we can think of them
as sitting still. The rate of encounter of each enzyme molecule with its substrate
will depend on the concentration of the substrate molecule. For example, some
abundant substrates are present at a concentration of 0.5 mM. Since pure water
is 55.5 M, there is only about one such substrate molecule in the cell for every
10 5 water molecules. Nevertheless, the active site on an enzyme molecule that
binds this substrate will be bombarded by about 500,000 random collisions with
the substrate molecule per second. (For a substrate concentration tenfold lower,
the number of collisions drops to 50,000 per second, and so on.) A random collision
between the active site of an enzyme and the matching surface of its substrate
molecule often leads immediately to the formation of an enzyme–substrate
complex. A reaction in which a covalent bond is broken or formed can now occur
extremely rapidly. When one appreciates how quickly molecules move and react,
the observed rates of enzymatic catalysis do not seem so amazing.
Two molecules that are held together by noncovalent bonds can also dissociate.
The multiple weak noncovalent bonds that they form with each other will
persist until random thermal motion causes the two molecules to separate. In
general, the stronger the binding of the enzyme and substrate, the slower their
rate of dissociation. In contrast, whenever two colliding molecules have poorly
matching surfaces, they form few noncovalent bonds and the total energy of association
will be negligible compared with that of thermal motion. In this case, the
two molecules dissociate as rapidly as they come together, preventing incorrect
and unwanted associations between mismatched molecules, such as between an
enzyme and the wrong substrate.
final distance
traveled
Figure 2–26 A random walk. Molecules
in solution move in a random fashion as a
result of the continual buffeting they receive
in collisions with other molecules. This
movement allows small molecules
to diffuse rapidly MBoC6 from m2.48/2.26 one part of the
cell to another, as described in the text
(Movie 2.3).
The Free-Energy Change for a Reaction, ∆G, Determines Whether
It Can Occur Spontaneously
Although enzymes speed up reactions, they cannot by themselves force energetically
unfavorable reactions to occur. In terms of a water analogy, enzymes
by themselves cannot make water run uphill. Cells, however, must do just that in
order to grow and divide: they must build highly ordered and energy-rich molecules
from small and simple ones. We shall see that this is done through enzymes
that directly couple energetically favorable reactions, which release energy and
produce heat, to energetically unfavorable reactions, which produce biological
order.
What do cell biologists mean by the term “energetically favorable,” and how
can this be quantified? According to the second law of thermodynamics the universe
tends toward maximum disorder (largest entropy or greatest probability).
Thus, a chemical reaction can proceed spontaneously only if it results in a net
increase in the disorder of the universe (see Figure 2–16). This disorder of the universe
can be expressed most conveniently in terms of the free energy of a system, a
concept we touched on earlier.
Free energy, G, is an expression of the energy available to do work—for example,
the work of driving chemical reactions. The value of G is of interest only when
a system undergoes a change, denoted ∆G (delta G). The change in G is critical
because, as explained in Panel 2–7 (pp. 102–103), ∆G is a direct measure of the
Figure 2–27 The structure of the cytoplasm. The drawing is approximately
to scale and emphasizes the crowding in the cytoplasm. Only the
macromolecules are shown: RNAs are shown in blue, ribosomes in green,
and proteins in red. Enzymes and other macromolecules diffuse relatively
slowly in the cytoplasm, in part because they interact with many other
macromolecules; small molecules, by contrast, diffuse nearly as rapidly as
they do in water (Movie 2.4). (Adapted from D.S. Goodsell, Trends Biochem.
Sci. 16:203–206, 1991. With permission from Elsevier.)
100 nm