Now gene expression is of course the last
way that we talk about controlling enzyme activity.
And the example I wanna have
for you here is the control
of a phenomenon in cells known as hypoxia.
Hypoxia is a situation where a cell finds itself
under a very low oxygen concentration
and when this happens cells produce a
transcription factor called HIF-1.
Now transcription factor,
of course, bind to DNA
and cause transcription to happen
of genes that they bind to.
So transcription factors are specific for
specific classes of genes, as we shall see.
HIF-1 induces expression of genes
that help the cell to deal
with hypoxic conditions.
Now this turns out to be interesting and it also
may have health implications; because,
cancer cells for example, are
frequently hypoxic meaning
that they have low oxygen circumstances. They
can be a cancer cell. They can be a regular cell.
But in either event
the result is the same.
What HIF-1 does is it favors
the production of proteins that
move glucose into cells.
GLUT1 and GLUT2 are proteins that are
stimulated whose syntheses is stimulated
by HIF-1. Now the movement of glucose
into cells is critical; because,
when oxygen concentrations are low the
cell needs more glucose to stay alive.
Anaerobic conditions cause
cells to go into fermentation
and fermentation is way less efficient
than oxidation of metabolites in presence of oxygen.
As an example, glucose in the
presence of oxygen when it is
oxidized produces 38 molecules of ATP.
Glucose in the absence of
oxygen in fermentation
only produces 2 molecules of ATP.
So if the oxygen concentrations for a cell are low
one of the ways a cell can
compensate for it is by synthesizing
proteins that bring
more glucose into cells
such as GLUT1 and GLUT3.
Well, that's not the entire
story; because, HIF-1
also induces the expression of other genes
that help to deal with that
increase in glucose coming in.
These are the following enzymes
in the glycolysis pathway
whose synthesis is stimulated
also by HIF-1. Hexokinase,
PFK, aldolase, glyceraldehyde-3-phosphate dehydrogenase,
phosphoglycerate kinase, enolase
and pyruvate kinase. That's
7 of the 10 enzymes of glycolysis.
whose synthesis is increased by HIF-1.
Telling us that the cell is
inducing gene expression
to help it adopt to the conditions
in which it finds itself
and that's a principle tenet of metabolic control.
Now I wanna extend this idea of
gene expression a little bit
further than simply the synthesis of protein;
because, gene expression really means
more than just that. So if we think
about gene expression so far we've
talked about how genes
are located in chromosomes
and how genes are transcribed and how
the control of that transcription
is a factor and it certainly is a factor.
We could imagine that the
more messenger RNA for a protein is made
that the more synthesis of
protein would result.
But there is a lot more
to it than just that.
So here we see this gene that
has been synthesized as a messenger RNA.
The efficiency with which that occurs we have
discussed already in other presentations
and that does the control the
levels of messenger RNA that are there.
That messenger RNA has to be processed.
We have talked about splicing, for example. We
have talked about capping and polyadenylation
and all of those have to happen in
order for messenger RNA in a eukaryotic cell
to function properly. The efficiency
with which that happens
is also a factor and it's determining
how much of a protein is synthesized.
That processed messenger RNA has
to make it to ribosome.
And so the efficiency with
which the ribosome actually
uses that messenger RNA to make protein
is yet another consideration
in the level of protein
that the cell is going to make.
RNA stability and the efficiency with which
the messenger RNA is transported from the nucleus
to the ribosome are factors to consider
in that efficiency process.
Next that messenger RNA has to be
translated into protein.
So we could imagine the efficiency of bringing in the
amino acids and joining them together in a ribosome
would be a factor in the final production of
how much protein is actually made.
But that's not the end of the story. There
is one other factor to consider in the
level of expression of a protein and
that is how stable the protein is.
The stability of the
protein is determined
by degraded enzymes inside of cells.
Proteins have a half life. Meaning that
they have a certain period of time
that will function before the
cell takes and degrades them.
So all of these steps that I have given
here in this pathway of gene expression
affect ultimately how much active
enzyme the cell has to work with.
The final consideration then
in the quantity of enzyme that's
found in the cell is actually its stability.
It turns out that proteins
are degraded inside of cells
and each protein that is in
a cell has a half life.
The half life determines how long it's active
and the protein that's made in a
cell won't be there forever.
So the stability control that's built into the
cell determines how long that protein will be around.
So each of the steps in this process ultimately determine
the amount of active enzymes that's present inside the cells.
Well, in this presentation I have gone through
3 important concepts in metabolic control.
First is allosterism where small molecules bind to
a protein and affect the protein's activity.
Second, zymogens where the cleavage
of peptide bonds can activate
proteins who have very dangerous activities
as far as the cell is concerned.
And third I have talked about
some considerations with respect to
gene expression and how gene
expression is actually more complex
then the simple synthesis of protein. I
hope this has been instructive to you
in learning about mechanisms for
controlling activity of genes.