Transcript Slide 1

Mic 428 - Lecture# 11
Regulation of Gene Expression
Outline
Requires review of Chapter 7 before coming to class.
The complexity of regulation.
Overview of regulation.
Constitutive and inducible enzymes.
Major modes of regulation in the cell:
1. Control of enzyme activity. Post translational control.
Mic 428 - Lecture# 11
Regulation of Gene Expression
Outline
Feedback inhibition.
Allosteric regulation and rate-limiting enzymes.
Types of allosteric regulation.
Isoenzymes.
2. Control of the amount of enzyme present:
transcriptional control and translational control (NEXT
CLASS).
Complexity of regulation
Hundreds of different enzymatic reactions
happening simultaneously.
Need to respond rapidly to changes in their
environment.
Complicated developmental pathways.
Some enzymes are needed in the same amount
under any growth condition.
CONSTITUTIVE
Some enzymes are not permanently needed in the
same amount under any growth condition.
INDUCIBLE
Two major modes of regulation:
Control of enzyme activity
After the enzyme has been produced
Post translational control
Control of the amount of an enzyme
At the level of transcription
Next class
At the level of translation
Overview of regulation
The product of gene A is enzyme A, which is synthesized constitutively and carries out its reaction.
Enzyme B is also synthesized constitutively but its activity can be inhibited. The synthesis of the
product of gene C can be prevented by control at the level of translation. The synthesis of the
product of gene D can be prevented by control at the level of transcription.
Regulation of enzyme activity
Inhibiting enzyme activity:
Enzymes are synthesized with full enzymatic activity and then
the activity is reduced or inhibited by certain compounds in
the cell.
These compounds are usually related to the metabolic pathway in
which the enzyme functions.
We have seen some of these cases. Do you remember any?
Feedback inhibition
Feedback inhibition
of enzyme activity
How is it possible for the end product of
a pathway to inhibit the enzyme that acts
on a substrate quite unrelated to it?
By means of allosteric regulation
The regulated enzyme is referred to as the ratelimiting enzyme.
Mechanism of enzyme inhibition by an allosteric
effector
In branched metabolic sequences, the
beginning of each branch is often
controlled allosterically
Feedback inhibition in a branched biosynthetic pathway
Types of allosteric regulation:
1. Simple feedback inhibition.
2. Concerted feedback inhibition.
3. Sequential feedback inhibition.
1. Simple feedback inhibition.
2. Concerted feedback inhibition.
A
B
C
D
E
F
More than one metabolite interacts with the enzyme
3. Sequential feedback inhibition.
A
Two or more metabolites
interact with an enzyme
B
C
D
F
G
E
H
Some biosynthetic pathways are regulated
by isoenzymes that catalyze the same
reaction but are subject to different
regulatory controls.
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.
Processing of preproinsulin
Protein splicing