The Internet Workbook: Question 2

Net Problem #2

Glycolysis and Human Pathology As before, you will want to read through the instructions completely, and perhaps print out a copy, before attempting this exercise.

Go to the Enzyme Catalogue (EC). One of the first things you will come across is a searchable index. Look for "pyruvate kinase" (PK). Unlike SCOP, complex keywords are welcome here.
A lot of entries will come up, in order of how well they match your query. You want the glycolytic enzyme, EC 2.7.1.40. Click on this. You can confirm this is the right enzyme by reading through the initial lines and seeing what reaction it catalyzes. If you've forgotten what reaction PK catalyzes, then go back to the page that contains the glycolytic pathway, check on the reaction, and then flip back to this page.
On the PK page you'll see a lot of different enzymes. These are all the known sequences from a variety of species. Locate the human enzyme (it's early in the list) and click on it. WARNING: you are embarking on a side-tour to a giant database in Switzerland. Although the Swiss servers are very fast, you may need to be a little patient. If everything is taking too long, you can skip down to (5).
There is a lot of useful information on this page. You can find the enzyme sequence, the enzyme structure, what types of domains are contained within the enzyme, and references about the enzyme. For now, though, we're going to focus on medical relevance. Find the hot key for "MIM" (Mendelian Inheritance in Man).
You've now entered a database that relates mutations or deletions in genes to the diseases that they cause. Realize that you've entered this database from an enzyme database: that is, you can learn about the enzymatic activity of a protein, and then relate this enzymatic activity to its physiological and medical relevance. If you had trouble getting to Switzerland, then just go into OMIM through http://www3.ncbi.nlm.nih.gov/Omim/searchomim.html and type the keyword "pyruvate kinase."
Now that you're here, let's see what diseases are associated with mutations in the PK gene. Read through the first paragraph; there will be things you won't understand, but you should be able to decipher much of it.
Answer the following questions (to be turned in):
1. Since PK is an absolutely essential gene for energy production from glucose, why don't people that have mutations die immediately?
2. What disease is associated with a deficiency in pyruvate kinase?
3. What group was affected by the disease? Why were researchers able to observe this?
4. What is the quarternary structure of the enzyme?
5. How are the liver and blood cell variants of the enzyme produced?
PK deficiency is the most common congenital disorder associated with glycolysis (as you would have seen if you had read farther in OMIM). This is probably because the glycolytic enzymes are absolutely essential, and either ova, sperm, or zygotes that contain mutations do not function or develop properly. However, using the tools you have learned you can now always search for relationships between enzymes and the genetic diseases with which they are associated.

Last updated: July 18, 1998
URL: http://biotech.icmb.utexas.edu/glycolysis/wwwquest2.html
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