On page 178, Moalem describes how increasing tolerance against drugs or alcohol can develop over time. This relates to Big Idea 3: Living systems store, retrieve, transmit, and respond to information essential to life processes. For example, if the liver senses that there is more alcohol in the body, then it will respond by producing more of the enzyme alcohol dehydrogenase.
Gene regulation is important in this function because a cell cannot make the enzyme whenever it wants to because it might not be needed. To have a higher chance to survive and reproduce, organisms must be able to use energy efficiently.
There are many possible ways that a gene can be regulated, but (please) discuss a possible mechanism on how the gene for alcohol dehydrogenase is regulated at the transcription level. (think: repressible/inducible operons, repressors, corepressors, activators, inducers, etc...)
How can the gene be regulated with respect to the chromatin structure? (acetylation/methylation) How does the option you picked change the structure of the chromatin, and thus the gene's ability to be expressed?
How about a possible way that the enzyme production can be controlled post-translationally?
Do you think that humans being able to produce alcohol dehydrogenase is a result of natural selection? I don't think there were breweries thousands of years ago, so how come we just happen to have the ability to break down alcohol into sugar? (your opinions are welcome)
(Hugo Lee; hlee3@students.d125.org)
Alcohol dehydrogenase is produced in the liver in humans, which means it is not regulated as an inducible operon, which is one of the methods of gene regulation in prokaryotic cells. However, eukaryotic cells do not use repressible and inducible operons to regulate gene expression. However, because the liver only produces alcohol dehydrogenase when alcohol is present, alcohol is activating the gene expression.
ReplyDeleteOne step where this is possible regulation could happen is at the chromatin structure level. Most likely, this would deal with acetylation. Alcohol may act as an allosteric activator for enzymes that acetylate the genes for alcohol dehydrogenase. However, the problem with regulating alcohol dehydrogenase production through acetylation is that it only unwinds the DNA. It does not directly lead to increased gene expression; it simply increases the chance it will happen. When alcohol enters the body, a cell needs to be able to directly trigger the production of alcohol dehydrogenase.
Similarly, regulation may have to deal with demethylation--- if the gene is demethylated, it will be more likely to be expressed. The sequence of methylation on the chromatin is called the epigenome. It is unlikely, however, that alcohol dehydrogenase is regulated through demethylation because the epigenome deals mainly with long term activation of genes. After the imprinting period during an organism’s youth, it is very difficult to change the epigenome of an organism.
Post translational regulation is likely only used when the alcohol dehydrogenase is no longer needed, so it is eaten up by a proteasome. However, this is not the primary way the alcohol hydrogenase gene is regulated because there is no point for an organism to go through translation and transcription if the protein is just going to be hydrolyzed because it is not needed.
The most likely way the production of alcohol dehydrogenase is regulated is through transcription initiation. Alcohol probably acts as an allosteric regulator to activator proteins. The activator proteins bind to the distal control elements of the enhancer. The activators then bind to mediator proteins and other general transcription factors to allow RNA polymerase to transcribe the gene. This way of regulation is most probable because the genes are only turned on when alcohol is present in the body.
This gene regulation directly relates to Big Idea 3. The cell, or cells, in this case the liver cells, take in information from the environment--- how much alcohol is in the body. If alcohol is present, the liver cells respond to the alcohol. The gene for alcohol dehydrogenase is activated, which in turn hydrolyzes alcohol and removes it from the system.
Gene regulation relates to alcohol in another way as well, through cancer. According to Science Daily on August 22, 2012, a possible link between alcohol and cancer has been found. When alcohol is process, through enzymes such as alcohol hydrogenase, one of the end products is acetaldehyde. Acetaldehyde is carcinogenic because it alters gene regulation. Acetaldehyde latches onto DNA and interferes with its regulation.
This may be a stretch, but the presence of the alcohol dehydrogenase gene could potentially go way back in human evolutionary history--- before we were even multi cellular organisms. Single cell eukaryotic organisms, through anaerobic respiration, produce alcohol when there is no oxygen. Thus, many of these single celled organisms likely have mechanisms to hydrolyze the alcohol they produce. The alcohol dehydrogenase gene could be result of our evolutionary past--- a part of our DNA that we don’t really NEED anymore (but some still want for the recreational consumption of alcohol).
(Dhruv Luthra, dluthra4@students.d125.org)