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

150 Chapter 3: Proteins
complex (see Figure 2–63), and elaborate controls are required to regulate when
and how rapidly each reaction occurs.
Regulation occurs at many levels. At one level, the cell controls how many
molecules of each enzyme it makes by regulating the expression of the gene that
encodes that enzyme (discussed in Chapter 7). The cell also controls enzymatic
activities by confining sets of enzymes to particular subcellular compartments,
whether by enclosing them in a distinct membrane-bounded compartment (discussed
in Chapters 12 and 14) or by concentrating them on a protein scaffold (see
Figure 3–77). As will be explained later in this chapter, enzymes are also covalently
modified to control their activity. The rate of protein destruction by targeted
proteolysis represents yet another important regulatory mechanism (see Figure
6–86). But the most general process that adjusts reaction rates operates through
a direct, reversible change in the activity of an enzyme in response to the specific
small molecules that it binds.
The most common type of control occurs when an enzyme binds a molecule
that is not a substrate to a special regulatory site outside the active site, thereby
altering the rate at which the enzyme converts its substrates to products. For example,
in feedback inhibition, a product produced late in a reaction pathway inhibits
an enzyme that acts earlier in the pathway. Thus, whenever large quantities of
the final product begin to accumulate, this product binds to the enzyme and slows
down its catalytic action, thereby limiting the further entry of substrates into that
reaction pathway (Figure 3–55). Where pathways branch or intersect, there are
usually multiple points of control by different final products, each of which works
to regulate its own synthesis (Figure 3–56). Feedback inhibition can work almost
instantaneously, and it is rapidly reversed when the level of the product falls.
A B C
X
Y
Z
negative
regulation
Figure 3–55 Feedback inhibition of a
single biosynthetic pathway. The end
product Z inhibits the first enzyme that is
unique to its synthesis and thereby controls
its own level in the cell. This is an example
of negative regulation.
MBoC6 m3.56/3.51
aspartate
aspartyl
phosphate
aspartate
semialdehyde
homoserine
lysine
methionine
threonine
isoleucine
Figure 3–56 Multiple feedback inhibition.
In this example, which shows the
biosynthetic pathways for four different
amino acids in bacteria, the red lines
indicate positions at which products feed
back to inhibit enzymes. Each amino acid
controls the first enzyme specific to its
own synthesis, thereby controlling its own
levels and avoiding a wasteful, or even
dangerous, buildup of intermediates. The
products can also separately inhibit the
initial set of reactions common to all the
syntheses; in this case, three different
enzymes catalyze the initial reaction, each
inhibited by a different product.