Essential Cell Biology 5th edition

150 CHAPTER 4 Protein Structure and Function
A B C
X
Y
Z
feedback
inhibitor
Figure 4−42 Feedback inhibition
regulates the flow through biosynthetic
pathways. B is the first metabolite in a
pathway that gives the end product Z.
Z inhibits the first enzyme that is specific
to its own synthesis ECB5 04.42 and thereby limits its
own concentration in the cell. This form
of negative regulation is called feedback
inhibition.
QUESTION 4–6
Consider the drawing in Figure
4−42. What will happen if, instead of
the indicated feedback,
A. feedback inhibition from
Z affects the step B → C only?
B. feedback inhibition from
Z affects the step Y → Z only?
C. Z is a positive regulator of the
step B → X?
D. Z is a positive regulator of the
step B → C?
For each case, discuss how useful
these regulatory schemes would be
for a cell.
The Catalytic Activities of Enzymes Are Often Regulated
by Other Molecules
A living cell contains thousands of different enzymes, many of which
are operating at the same time in the same small volume of the cytosol.
By their catalytic action, enzymes generate a complex web of metabolic
pathways, each composed of chains of chemical reactions in which the
product of one enzyme becomes the substrate of the next. In this maze of
pathways, there are many branch points where different enzymes compete
for the same substrate. The system is so complex that elaborate
controls are required to regulate when and how rapidly each reaction
occurs.
A common type of control occurs when a molecule other than a substrate
specifically binds to an enzyme at a special regulatory site, altering the
rate at which the enzyme converts its substrate to product. In feedback
inhibition, for example, an enzyme acting early in a reaction pathway
is inhibited by a molecule produced later in that pathway. Thus, whenever
large quantities of the final product begin to accumulate, the product
binds to an earlier enzyme and slows down its catalytic action, limiting
further entry of substrates into that reaction pathway (Figure 4−42).
Where pathways branch or intersect, there are usually multiple points
of control by different final products, each of which regulates its own
synthesis (Figure 4−43). Feedback inhibition can work almost instantaneously
and is rapidly reversed when product levels fall.
aspartate
aspartyl
phosphate
aspartate
semialdehyde
homoserine
Figure 4−43 Feedback inhibition at
multiple points regulates connected
metabolic pathways. The biosynthetic
pathways for four different amino acids in
bacteria are shown, starting from the amino
acid aspartate. The red lines indicate points
at which products feed back to inhibit
enzymes and the blank boxes represent
intermediates in each pathway. In this
example, each amino acid controls the first
enzyme specific to its own synthesis, thereby
limiting its own concentration and avoiding
a wasteful buildup of intermediates. Some
of the products also separately inhibit the
initial set of reactions common to all the
syntheses. Three different enzymes catalyze
the initial reaction from aspartate to aspartyl
phosphate, and each of these enzymes is
inhibited by a different product.
lysine
methionine
threonine
isoleucine