Gene Expression Control – Metabolic Control of Enzyme Activity

by Kevin Ahern, PhD

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    00:00 Now gene expression is of course the last way that we talk about controlling enzyme activity.

    00:06 And the example I wanna have for you here is the control of a phenomenon in cells known as hypoxia.

    00:13 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.

    00:27 Now transcription factor, of course, bind to DNA and cause transcription to happen of genes that they bind to.

    00:35 So transcription factors are specific for specific classes of genes, as we shall see.

    00:41 HIF-1 induces expression of genes that help the cell to deal with hypoxic conditions.

    00:46 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.

    00:59 But in either event the result is the same.

    01:03 What HIF-1 does is it favors the production of proteins that move glucose into cells.

    01:11 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.

    01:28 Anaerobic conditions cause cells to go into fermentation and fermentation is way less efficient than oxidation of metabolites in presence of oxygen.

    01:41 As an example, glucose in the presence of oxygen when it is oxidized produces 38 molecules of ATP.

    01:50 Glucose in the absence of oxygen in fermentation only produces 2 molecules of ATP.

    01:55 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.

    02:08 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.

    02:20 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.

    02:41 whose synthesis is increased by HIF-1.

    02:44 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.

    02:54 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.

    03:17 We could imagine that the more messenger RNA for a protein is made that the more synthesis of protein would result.

    03:26 But there is a lot more to it than just that.

    03:27 So here we see this gene that has been synthesized as a messenger RNA.

    03:33 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.

    03:43 That messenger RNA has to be processed.

    03:45 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.

    04:03 That processed messenger RNA has to make it to ribosome.

    04:07 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.

    04:20 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.

    04:33 Next that messenger RNA has to be translated into protein.

    04:35 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.

    04:45 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.

    04:54 The stability of the protein is determined by degraded enzymes inside of cells.

    05:03 Proteins have a half life. Meaning that they have a certain period of time that will function before the cell takes and degrades them.

    05:09 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.

    05:19 The final consideration then in the quantity of enzyme that's found in the cell is actually its stability.

    05:26 It turns out that proteins are degraded inside of cells and each protein that is in a cell has a half life.

    05:32 The half life determines how long it's active and the protein that's made in a cell won't be there forever.

    05:38 So the stability control that's built into the cell determines how long that protein will be around.

    05:46 So each of the steps in this process ultimately determine the amount of active enzymes that's present inside the cells.

    05:53 Well, in this presentation I have gone through 3 important concepts in metabolic control.

    05:58 First is allosterism where small molecules bind to a protein and affect the protein's activity.

    06:02 Second, zymogens where the cleavage of peptide bonds can activate proteins who have very dangerous activities as far as the cell is concerned.

    06:13 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.

    About the Lecture

    The lecture Gene Expression Control – Metabolic Control of Enzyme Activity by Kevin Ahern, PhD is from the course Metabolic Control.

    Included Quiz Questions

    1. Nucleotide
    2. Transcriptional
    3. RNA stability
    4. Translational
    1. HIF-1
    2. HIF-2
    3. GLUT1
    4. GLUT2
    5. Two transcription factors called GLUT1 and GLUT3
    1. The HIF-1 factor helps the cell to combat with toxic conditions originated due to higher oxygen levels
    2. Under hypoxia condition, the regular cells, as well as cancer cells, synthesize the transcription factor called as HIF-1
    3. HIF-1 factor favors elevated levels of expression of the seven enzymes of the glycolysis pathway during hypoxia condition
    4. HIF-1 factor binds to the particular class of genes in the DNA which help in the survival of cell at low oxygen concentrations
    5. The transcription factor HIF-1 helps in the movement of glucose to the interior of the cell by favoring the formation of GLUT1 and GLUT3 proteins
    1. Controlling the process of transcription and hence synthesis of a specific mRNA and protein molecules
    2. Controlling the permeabilities of the cell membrane and mitochondrial membrane for water
    3. Controlling the fluidity of cell membrane by regulating the ion movement
    4. Controlling the amounts of energy in the form of ATP and GTP
    5. Controlling the amounts of rRNA and tRNA to regulate

    Author of lecture Gene Expression Control – Metabolic Control of Enzyme Activity

     Kevin Ahern, PhD

    Kevin Ahern, PhD

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