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Increased Gene Expression vs Upregulation of an Enzyme


Upperninety8

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So some context, I haven't taken genetics. However, in a class the other day a professor tried to differentiate the two and left me pretty confused.

From my understanding, increased gene expression will result in an increase in the protein product that a gene is coding for. Meaning that if you increased expression of a gene that codes for an enzyme, it would result in upregulation of that enzyme.

^What's wrong with my thinking on this?

If you want specifics, the discussion was on serum cholesterol and what physiologic effects it would have. The professor (to the best of my understanding) was explaining that low serum cholesterol would result in increased LDL-Receptors but would not result in upregulation of HMG-COA Reductase (the rate limiting step of cholesterol synthesis) He said that you would see increased expression, but not upregulation. But by increasing the expression of a gene that codes for HMG-COA reductase I thought the end result would be upregulation of the enzyme.

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It sounds like he is describing the difference between "amount" of protein versus "activity" of the protein. Many proteins have different activity levels depending upon modifications made to them. For instance, the addition of a phosphate group (called phosphorylation) to a protein may activate, deactivate, or increase/decrease its activity. Secondly, changes in gene expression do not automatically result in increased protein production. Many genes are regulated as much, if not more at the level of translation than they are at the level of gene expression.

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It sounds like he is describing the difference between "amount" of protein versus "activity" of the protein. Many proteins have different activity levels depending upon modifications made to them. For instance, the addition of a phosphate group (called phosphorylation) to a protein may activate, deactivate, or increase/decrease its activity. Secondly, changes in gene expression do not automatically result in increased protein production. Many genes are regulated as much, if not more at the level of translation than they are at the level of gene expression.

 

Yeah I get that he's trying to describe that difference, I guess maybe I need to rephrase this...

 

I've done the research, and you do see increased HMG-CoA reductase mRNA in the presence of low serum cholesterol. So won't this increase in mRNA lead to increased production of the enzyme?

 

A snippit from one of the articles I looked through...

"Studies using cultured cells [10], showed that a reduction in intracellular cholesterol levels resulted in a dual response: 1. an increase in the production of mRNA for HMG-CoA reductase to synthesize more cholesterol for the depleted cell and 2. an increase in the amount of mRNA for the LDL-r in order to increase exogenous cho- lesterol uptake."

 

Hmm as far as the second part of your answer goes... I understand that things are regulated on many different levels, but I thought "increased expression" was synonymous with increased production of the genetic product. I understand that this won't always lead to an increase in the number of enzymes because we could be talking about a gene that codes for something different, but I thought gene expression is the process by which information on a gene is used to assemble it's corresponding product. If this were so, wouldn't increased gene expression lead to increased product?

 

Again, I haven't taken genetics, just picked up bits and pieces from other courses. I could be way off, but this was my understanding of it.

Edited by Upperninety8
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