Regulation and Control of Metabolism in Bacteria (page 5)
(This chapter has 5 pages)
© Kenneth Todar, PhD
Enzyme Induction is still considered a form of negative control
the effect of the regulatory molecule (the active repressor) is to
or downregulate the rate of transcription. Catabolite
repression is a
type of positive control of transcription, since a regulatory
affects an increase (upregulation) in the rate of transcription
of an operon. The process was discovered in E. coli and was
referred to as the glucose effect because it was found that
repressed the synthesis of certain inducible enzymes, even though
inducer of the pathway was present in the environment. The discovery
made during study of the regulation of lac operon in E. coli.
glucose is degraded by constitutive enzymes and lactose is initially
by inducible enzymes, what would happen if the bacterium was grown in
amounts of glucose and lactose? A plot of the bacterial growth rate
in a diauxic growth curve which showed two distinct phases of
growth (Figure 9). During the first phase of exponential growth, the
utilize glucose as a source of energy until all the glucose is
Then, after a secondary lag phase, the lactose is utilized during a
stage of exponential growth.
Figure 9. The Diauxic Growth
Curve of E. coli grown in limiting concentrations of a mixture
glucose and lactose
During the period of glucose utilization, lactose is not utilized
the cells are unable to transport and cleave the disaccharide lactose.
Glucose is always metabolized first in preference to other sugars. Only
after glucose is completely utilized is lactose degraded. The lactose
is repressed even though lactose (the inducer) is present. The
rationale is that glucose is a better source of energy than lactose
its utilization requires two less enzymes.
Only after glucose is exhausted are the enzymes for lactose
synthesized. The secondary lag during diauxic growth represents the
required for the complete induction of the lac operon and synthesis of
the enzymes necessary for lactose utilization (lactose permease and
Only then does bacterial growth occur at the expense of lactose. Since
the availability of glucose represses the enzymes for lactose
this type of repression became known as catabolite repression
the glucose effect.
Glucose is known to repress a large number of inducible enzymes in
different bacteria. Glucose represses the induction of inducible
by inhibiting the synthesis of cyclic AMP (cAMP), a nucleotide
is required for the initiation of transcription of a large number of
enzyme systems including the lac operon.
The role of cyclic a cAMP is complicated. cAMP is required to
an allosteric protein called CAP (catabolite activator protein)
which binds to the promoter CAP site and stimulates the binding of RNAp
polymerase to the promoter for the initiation of transcription. Thus,
efficiently promote gene transcription of the lac operon, not only must
lactose be present to inactivate the lac repressor, but cAMP must be
to bind to CAP which binds to DNA to facilitate transcription. In
presence of glucose, adenylate cyclase (AC) activity is blocked. AC
is required to synthesize cAMP from ATP. Therefore, if cAMP levels are
low, CAP is inactive and transcription does not occur. In
absence of glucose, cAMP levels are high, CAP is activated by cAMP,
and transcription occurs (in the presence of lactose).
Many positively controlled promoters, such as the lac promoter, are
not fully functional in the presence of RNAp alone and require
by CAP. CAP is encoded by a separate Regulatory gene, and is present in
constitutive levels. CAP is active only in the presence of cAMP. The
of cAMP to CAP causes a conformational change in the protein allowing
to bind to the promoter near the RNAp binding site. CAP can apparently
interact with RNAp to increase the rate of operon transcription about
control of the lac operon is illustrated in Figure 10.
Figure 10. Catabolite
is positive control of the lac operon. The effect is an increase in the
rate of transcription. In this case, the CAP protein is activated by
to bind to the lac operon and facilitate the binding of RNA polymerase
to the promoter to transcribe the genes for lactose utilization.
As a form of catabolite repression, the glucose effect serves a useful
function in bacteria: it requires the cells to use the best available
of energy. For many bacteria, glucose is the most common and readily
substrate for growth. Thus, it inhibits indirectly the synthesis of
that metabolize poorer sources of energy.
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