Transcript lecture notes-molecular biology-cell regulation

Metabolic Regulation
-
.
-
:
- Enzyme activity
- Cell surface receptors
Metabolic Regulation
Genetic Level Regulation:
Control which protein is synthesized through adjusting
the rate of transcription of that gene:
Feedback repression: The
activity accumulates and blocks t
of enzymatic
.
For repression, the
is required which can
bind to the operator region and hinder RNA polymerase
binding.
The repressor protein can block transcription
when
bound to the
(typically the end product
of the pathway).
Normal Transcription
DNA template
Promoter
Operator
Gene 1
Gene 2
Gene 3
m-RNA
RNA polymerase
repressor
inactive
Transcription Blocked
DNA template
Promoter
RNA polymerase
Operator
Gene 1
repressor
corepressor
active
Gene 2
Gene 3
Genetic Organization of the Tryptophan Operon
DNA template
encoding related enzymes for tryptophan synthesis
from chorismate.
encoding repressor
Only when the repressor binds with tryptophan, it can bind
on the operator region and block the transcription.
Operon: In prokaryotes, a set of genes, encoding proteins with
related functions, under the control of a single promoteroperator.
Metabolic regulation
Genetic Level Regulation:
Induction: a
( often a substrate for a
pathway) accumulates and acts as an inducer of
transcription.
The inducer will bind the repressor protein, and
the complex is inactive as a repressor.
Transcription Blocked
Promoter
Operator
RNA polymerase
Gene 1
repressor
Gene 2
Gene 3
DNA template
Transcription Permitted
DNA template
Promoter
Operator
Gene 1
Gene 2
Gene 3
m-RNA
RNA polymerase
repressor
Inducer
Example
• Inducer: allolactose modified from lactose in the cell.
e.g. The lactose operon controls the synthesis of
three proteins (Lac z (lactase), lac y, lac a )
involved in lactose utilization as a carbon and
energy source in E. coli.
Lac i
Promoter
Operator
Lac z
Lac y
Lac a
m-RNA
RNA polymerase
repressor
Lac i encoding repressor.
allolactose
Catabolite Repression (Glucose Effect)
• Inducer: allolactose modified from lactose in the cell.
• Induction of allolactose might not be sufficient for
maximum transcription if a carbon-energy source (e.g.
glucose) preferred to lactose is present.
• Only when glucose is depleted, the cell will expend
energy to create a pathway to utilize the less favorable
carbon-energy source lactose.
Metabolic Regulation
Catabolite Repression (glucose effect)
When the cell has an energetically favorable
carbon-energy source (e.g. glucose) available,
it will not expend significant energy to create a
pathway for utilization of a less favorable
carbon-energy source;
it will not transcript the related enzyme for such
reaction.
Metabolic Regulation
Genetic Level Regulation:
- Some genes are regulated.
- Others are not (constitutive):
their gene products are made at a relatively
constant rate irrespective of changes in growth
conditions.
( enzymes are expected to use under almost any
conditions such as that involved in glycolysis)
Metabolic Regulation
Cellular Level Regulation - Metabolic Pathway Control:
- The
enzyme activity.
can be controlled by
- The activity of allosteric enzymes can be controlled
by effectors including inhibitors and activators.
- Most often the
reaction in the pathway is
inhibited by accumulation of
:
feedback inhibition or end-product inhibition.
What are the differences
between feedback repression
and feedback inhibition?
Feedback
repression
Regulation level Genetic: RNA
transcription
Complex formed End product +
repressor
Feedback
inhibition
Cellular:
Activity of
enzyme
End product +
enzyme
Effect
Operator on DNA
template occupied
by the complex
Reduced enzyme
activity
Consequence
Blocked
Transcription
The respective
reaction is
inhibited.
Metabolic Regulation
Cellular level- metabolic pathway controls:
The activities of a group of enzymes (pathway) can be
controlled.
-
Isozymes
-
Concerted feedback
-
Sequential feedback
Cumulative feedback
Please refer to the textbook p.123.
Metabolic Regulation
Cellular level- metabolic pathway controls through:
- Isozymes
- A number of separate enzymes initially carry out the
same conversion, each of which is sensitive to
inhibition by a different end product.
The common pathway leading
to the synthesis of the
aromatic amino acids contains
three isozymes. Each of
these enzymes is specifically
feedback-inhibited by one of
the aromatic amino acids.
Note how an excess of all
three amino acids is required
to completely shut off the
synthesis of DAHP.
Metabolic Regulation
- Concerted feedback inhibition
More than one end product or all end products must be
present in excess to repress the first enzyme.
Metabolic Regulation
- Sequential feedback inhibition
The common steps are inhibited by the product before
the branch, and the first enzyme of each branch is
inhibited by the branch product.
High levels of P1 and P2 inhibit enzyme E3 and E4,
respectively → M3 will accumulate →the pathway is
inactivated if both P1 and P2 are high.
P1
M1 X
E1
M2
M3
E2
X
M4
E3
X E4
M5
P2
Sequential Feedback Inhibition
Metabolic Regulation
- Cumulative feedback inhibition or cooperative
feedback inhibition
- A single allosteric enzyme may have effector sites for several end products of a pathway;
- each effector causes only partial inhibition.
- Full inhibition is a cumulative effect.
Concerted
Cumulative
Inosine 5-mono-phosphate (IMP)
Summary of Metabolic Regulation
Metabolic regulation:
• Genetic level: control transcription of genes
(repression, induction and catabolic
repression (glucose effect))
• Cellular level:
- Enzyme activity: feedback inhibition
Isoenzyme, concerted feedback,
sequential and cumulative feedback inhibition