Essential Cell Biology 5th edition

Free Energy and Catalysis
99
Figure 3−22 The cytosol is crowded with various molecules.
Only the macromolecules, which are drawn to scale and
displayed in different colors, are shown. Enzymes and other
macromolecules diffuse relatively slowly in the cytosol, in part
because they interact with so many other macromolecules. Small
molecules, by contrast, can diffuse nearly as rapidly as they do
in water (see Movie 1.2). (From S.R. McGuffee and A.H. Elcock,
PLoS Comput. Biol. 6(3): e1000694, 2010.)
proceeds rapidly to completion because the total ΔG° for the series of
sequential reactions has a large negative value.
Forming a sequential pathway, however, is not the answer for many
other metabolic needs. Often the desired reaction is simply X → Y, without
further conversion of Y to some other product. Fortunately, there are
other, more general ways of using enzymes to couple reactions together,
involving the production of activated carriers that can shuttle energy
from one reaction site to another, as we discuss shortly.
Enzyme-catalyzed Reactions Depend on Rapid
Molecular Collisions
Thus far we have talked about chemical reactions as if they take place
in isolation. But the cytosol of a cell is densely packed with molecules of
various shapes and sizes (Figure 3−22). So how do enzymes and their
substrates, which are present in relatively small amounts in the cytosol
of a cell, manage to find each other? And how do they do it so quickly?
Observations indicate that a typical enzyme can capture and process
about a thousand substrate molecules every second.
Rapid binding is possible because molecular motions are enormously
fast—very much faster than the human mind can easily imagine. Because
of heat energy, molecules are in constant motion and consequently
will explore the cytosolic space very efficiently by wandering randomly
through it—a process called diffusion. In this way, every molecule in the
cytosol collides with a huge number of other molecules each second.
As these molecules in solution collide and bounce off one another, an
individual molecule moves first one way and then another, its path constituting
a random walk (Figure 3−23).
Although the cytosol of a cell is densely packed with molecules of various
shapes and sizes, experiments in which fluorescent dyes and other
labeled molecules are injected into the cell cytosol show that small
organic molecules diffuse through this aqueous gel nearly as rapidly as
they do through water. A small organic molecule, such as a substrate,
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
limited distances in the cell.
Because proteins diffuse through the cytosol much more slowly than do
small molecules, the rate at which an enzyme will encounter its substrate
depends on the concentration of the substrate. The most abundant
substrates are present in the cell at a concentration of about 0.5 mM.
Because pure water is 55 M, there is only about one such substrate molecule
in the cell for every 10 5 water molecules. Nevertheless, the site on
an enzyme that binds this substrate will be bombarded by about 500,000
random collisions with the substrate every second! For a substrate concentration
tenfold lower (0.05 mM), the number of collisions drops to
50,000 per second, and so on. These incredibly numerous collisions play
a critical role in life’s chemistry.
ECB5 n3.101/3.22
QUESTION 3–4
25 nm
For the reactions shown in Figure
3−21, sketch an energy diagram
similar to that in Figure 3−12 for
the two reactions alone and for
the combined reactions. Indicate
the standard free-energy changes
for the reactions X → Y, Y → Z,
and X → Z in the graph. Indicate
how enzymes that catalyze these
reactions would change the energy
diagram.
net distance
traveled
Figure 3−23 A molecule traverses
the cytosol by taking a random walk.
Molecules in solution move in a random
fashion due to the continual buffeting they
receive in collisions with other molecules.
This movement allows small molecules to
ECB5 e3.22/3.23
diffuse rapidly throughout the cell cytosol
(Movie 3.2).