Regulation and Control of Metabolism in Bacteria (page 2)
(This chapter has 5 pages)
© Kenneth Todar, PhD
Feedback inhibition (or end product inhibition) is a
for the inhibition of preformed enzymes that is seen primarily
the regulation of whole biosynthetic pathways, e.g. pathways involved
the synthesis of the amino acids. Such pathways usually involve many
steps, and the final (end) product is many steps removed from the
substrate. By this mechanism, the final product is able to feed back to
the first step in the pathway and to regulate its own biosynthesis.
In feedback inhibition, the end product of a biosynthetic pathway
the activity of the first enzyme that is unique to the pathway, thus
production of the end product. The first enzyme in the pathway is an
enzyme. Its allosteric site will bind to the end product (e.g. amino
of the pathway which alters its active site so that it cannot mediate
enzymatic reaction which initiates the pathway. Other enzymes in the
remain active, but they do not see their substrates. The pathway is
down as long as adequate amounts of the end product are present. If the
end product is used up or disappears, the inhibition is relieved, the
regains its activity, and the organism can resume synthesis of the end
product. Thus, if a E. coli
bacterium swims out of a glucose minimal medium
into milk or some other medium rich in growth factors, the bacterium
stop synthesizing any of the essential metabolites that are made
directly from the new environment.
One of the most intensely studied bacterial pathways is the pathway
of tryptophan biosynthesis (Figure 3). The pathway of tryptophan
is regulated by feed back inhibition. Tryptophan is the effector
for allosteric enzyme a. When the end product of the pathway
attaches to enzyme a, the
enzyme is inactive and can no longer join glutamine
and chorismic acid into anthranilate. If tryptophan is disjoined from
enzyme the pathway is resumed, and tryptophan synthesis will continue.
Tryptophan biosynthesis is also regulated at a genetic level by the
of enzyme repression (below) and attenuation.
Note: In the case of feedback inhibition (above), the signal
tryptophan, is a negative effector of Enzyme a in the pathway of tryptophan
biosynthesis, because when it binds to Enzyme a, it inactivates the enzyme.
In enzyme repression (below) tryptophan is a signal molecule that acts
as a positive effector of the trp repressor protein because when it
to the repressor it activates the protein, so that it binds to the trp
Figure 3. The pathway of
biosynthesis in E. coli. The pathway is regulated by the
of feedback inhibition. Tryptophan (trp), the end product of the
is the effector molecule that binds to the allosteric site of Enzyme a,
the first enzyme in the pathway. When trp is bound to the enzyme the
(active) site of Enzyme a is altered so that it is unable to react with
its substrates and the synthesis of anthranilate is inhibited.
If a metabolic pathway branches, leading to the synthesis of two
acids, each end product (amino acid) can control its own synthesis
affecting the other (Figure 4). For example, the amino acids proline
arginine are both synthesized from glutamic acid. Each amino acid can
the first enzyme unique to its own synthesis without affecting the
so that a surplus of arginine will not shut off the synthesis
of proline and vice versa.
Figure 4. Generalized scheme
for regulation of a branched metabolic pathway by the process of