Transcript Regulation and Control of Metabolism in Bacteria

REGULATION AND CONTROL OF
METABOLISM IN BACTERIA
Yunika S
10406024
Bacterial Adaptation to the
Nutritional and Physical Environment




Within limits, bacteria can react to changes in their
environment through changes in patterns of structural
proteins, transport proteins, toxins, enzymes, etc., which
adapt them to a particular ecological situation.
Bacteria have developed sophisticated mechanisms for the
regulation of both catabolic and anabolic pathways.
Generally, bacteria do not synthesize degradative
(catabolic) enzymes unless the substrates for these enzymes
are present in their environment.
Similarly, bacteria have developed diverse mechanisms for
the control of biosynthetic (anabolic) pathways. Bacterial
cells shut down biosynthetic pathways when the end product
of the pathway is not needed or is readily obtained by
uptake from the environment.
Conditions Affecting Enzyme
Formation in Bacteria



Constitutive enzymes are always produced by cells
independently of the composition of the medium in which the
cells are grown.
Inducible enzymes are produced ("turned on") in cells in
response to a particular substrate; they are produced only
when needed. The substrate, or a compound structurally
similar to the substrate, evokes formation of the enzyme and
is sometimes called an inducer.
A repressible enzyme is one whose synthesis is
downregulated or "turned off" by the presence of (for
example) the end product of a pathway that the enzyme
normally participates in. In this case, the end product is
called a corepressor of the enzyme.
Regulation of Enzyme Reactions

a.
b.

In bacterial cells, enzymatic reactions may be regulated
by two unrelated modes:
control or regulation of enzyme activity (feedback
inhibition or end product inhibition)
control or regulation of enzyme synthesis, including
end-product repression, which functions in the
regulation of biosynthetic pathways, and enzyme
induction and catabolite repression, which regulate
mainly degradative pathways.
The processes which regulate the synthesis of enzymes
may be either a form of positive control or negative
control.
Regulation of Enzyme Reactions
(Cont.)


End-product repression and enzyme induction are
mechanisms of negative control because they lead
to a decrease in the rate of transcription of
proteins.
Catabolite repression is considered a form of
positive control because it affects an increase in
rates of transcription of proteins.
Regulation of Enzyme Reactions
(Cont.)
Allosteric Proteins



The regulatory proteins that control metabolic pathways
involving end product repression, enzyme induction and
catabolite repression are allosteric proteins.
An allosteric protein has an active (catalytic) site and
an allosteric (effector) site.
The active site binds to the substrate of the enzyme and
converts it to a product. The allosteric site is occupied
by some small molecule, called allosteric or effector
molecule, which is not a substrate, and can affect the
active site.
Allosteric Proteins (cont.)
Allosteric Proteins (cont.)


In the case of enzyme repression, a positive effector
molecule (called a corepressor) binds to the
allosteric regulatory protein and activates its ability
to bind to DNA.
In the case of enzyme induction a negative effector
molecule (called an inducer) binds to the allosteric
site, causing the active site to change conformation
thereby detaching the protein from its DNA binding
site.
Feedback Inhibition


In feedback inhibition (or end product inhibition),
the end product of a biosynthetic pathway inhibits
the activity of the first enzyme that is unique to the
pathway, thus controlling production of the end
product.
The first enzyme in the pathway is an allosteric
enzyme. Its allosteric site will bind to the end
product of the pathway which alters its active site so
that it cannot mediate the enzymatic reaction which
initiates the pathway.
The pathway of tryptophan biosynthesis in E. coli.
The signal molecule, 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.
The pathway of proline and arginine biosynthesis
Enzyme Repression


Enzyme repression is a form of negative control
(down-regulation) of bacterial transcription. This
process, along with that of enzyme induction, is
called negative control because a regulatory
protein brings about inhibition of mRNA synthesis
which leads to decreased synthesis of enzymes.
The genes for tryptophan biosynthesis in Escherichia
coli are organized on the bacterial chromosome in
the tryptophan operon (trp operon).
Genetic organization of the Trp operon and its control
elements.
Repression of the trp operon. In the presence of tryptophan the
trp operon is repressed because trp activates the repressor.
Transcription is blocked because the active repressor binds to
the DNA and prevents binding of RNA polymerase.
Derepression of the trp operon. In the absence of trp the
inactive repressor cannot bind to the operator to block
transcription. The cell must synthesize the amino acid.
Enzyme Induction


In the process of enzyme induction, the substrate,
or a compound structurally similar to the substrate,
evokes the formation of enzyme(s) which are usually
involved in the degradation of the substrate.
Enzymes that are synthesized as a result of genes
being turned on are called inducible enzymes and
the substance that activates gene transcription is
called the inducer.
The Lac operon and its control elements
Enzyme Induction. Induction (or derepression) of the lac
operon.
Catabolite Repression


Catabolite repression is a type of positive control
of transcription, since a regulatory protein affects
an increase (upregulation) in the rate of
transcription of an operon.
The process was discovered in E. coli and was
originally referred to as the glucose effect.
because it was found that glucose repressed the
synthesis of certain inducible enzymes, even
though the inducer of the pathway was present in
the environment.
The Diauxic Growth Curve of E. coli grown in limiting concentrations of a mixture of
glucose and lactose
Glucose is always metabolized first in preference to other sugars. Only after glucose is
completely utilized is lactose degraded. The lactose operon is repressed even though
lactose (the inducer) is present. The secondary lag during diauxic growth represents
the time required for the complete induction of the lac operon and synthesis of the
enzymes necessary for lactose utilization (lactose permease and beta-galactosidase).
Catabolite Repression (cont.)


Glucose represses the induction of inducible operons by
inhibiting the synthesis of cyclic AMP (cAMP), a
nucleotide that is required for the initiation of
transcription of a large number of inducible enzyme
systems including the lac operon.
In the 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 the
absence of glucose, cAMP levels are high, CAP is
activated by cAMP, and transcription occurs (in the
presence of lactose).

cAMP is required to activate 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
Catabolite repression 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 cAMP to bind to the lac operon and
facilitate the binding of RNA polymerase to the promoter to
transcribe the genes for lactose utilization.
Terima Kasih