CHEM 342 -
Introduction to Biochemistry
Assignment - Due Last Friday of the Semester
Pauling introduced the concept of molecular disease by
demonstrating that the gene for sickle cell anemia was directly related
a chemical alteration of hemoglobin in the red blood cells of affected
individuals. A few years later, Vernon
Ingram identified a single amino acid replacement at position 6 of
the beta chains of sickle cell hemoglobin (HbS) and showed
that the sequence of the remaining 145 amino acids of the beta chains
and all 141 amino acids in the alpha chains of hemoglobin were
unchanged compared to normal hemoglobin (HbA). Subsequently, others
determined the exact nucleotide substitution mutation in the beta
globin gene possessed by sickle cell patients.
These discoveries prompted a stampede of sorts to
discover other hemoglobin variants and the corresponding mutations in
DNA. There are now on the order of 1000 different mutations known
to affect the amino acid sequence or production of hemoglobin. While
many of these are single-base-substitution mutations, deletions, and
insertions that have little or no clinical effects, the consequences of
others vary from benign to severe, as in the case of thalassemias. Many
medical biochemists have made a career studying these usually
Using a list
of hemoglobinopathies (alpha-chain,
pick an interesting example to investigate as the basis for
a 5+ page, double-spaced, well-organized report. Select a variant
that no one else in class has selected. Your report should have the
To prepare for this assignment, each group should
arrange a time before April 25 to meet for 30-60 minutes with Catherine
Wojewodzki, a science librarian in 117C Morris Library (831-4240, or
Cathyw at udel.edu) who is familiar with this project and can provide
assistance in tracking down the information you need. In the past,
students have had problems because they did not take full advantage of
the resources available. You will need to develop
these library research skills as part of your undergraduate education. (They go well beyond "Googling" the internet.)
- A description of the mutation and its
consequences for hemoglobin structure, function, and
stability. (Append a photocopy of the title page of the original
article describing the mutation and/or variant hemoglobin.)
- Where appropriate, include a computer-generated image
of the three-dimensional structure of hemoglobin showing the location
or region of the molecule affected. Be sure that the illustration is informative
and has an explanatory caption to go with it.
Tapan Patel, has created a web-site that will lead you
step by step through the process of making a useful computer
your hemoglobin variant.
- Describe any clinical and/or functional effects
of the mutation.
- Provide citations to all
references and illustrations (if not original) using the standard
citation format of the Journal
of Biological Chemistry. Part of the purpose of this assignment is
for you to demonstrate your ability to find, use, and properly document
information from the library. Inclusion of 5 relevant citations to
research articles is the minimum for a grade of "C."
- Work to give your specific topic some general relevance by
relating it to general principles and other hemoglobin variants.
This assignment will be evaluated for its composition,
content, clarity of presentation, and depth of your analysis. An "A
paper" must go beyond simple reporting of information. For
example, a molecular graphics representation of your hemoglobin variant
showing the location of any mutational modification, but make sure it
shows something worth seeing.
Remember, this should be your synthesis
of the information, not a paraphrasing of the
words of others. Late papers will not be accepted wityhout a
Other Options: Students
who would rather explore aspects of hemoglobin function, evolution, or
properties of unusual hemoglobins from other sources may do so in
consultation with Dr. White. There are related topics available such as
Glucose-6-P deficiency (favism).
1. Nobel Prize winner, Max Perutz
(1914-2002), spent 20 years working on the X-ray crystallography of
hemoglobin before he finally determined its three-dimentional structure
in 1957. There after he spent much of the rest of his life studying the
structure of interesting hemoglobin variants. One strategy you might
to search and examine the publications of Max Perutz on PubMed or
the Web of
Science. Remember, you can often get full text copies through the
University of Delaware's electronic journal
subscriptions. You may also find some of the sites
linked to the course home page of use.
2. Log on to one of the protein data bases and
explore their reference lists and tabulations of hemoglobin varaints.
Some data bases include: NCBI
(National Center for Biomedical Information), PDB (Protein Data Bank, or Swiss-Prot (Swiss protein data
base). Simply start your search at any of these by typing in "human
hemoglobin" and follow the links of interest.
3. Feel free to discuss your ideas and any
difficulties you have with me (Dr. White) preferably well before the
Making your request: All
requests must be cleared by sending an e-mail message to Dr. White who
will check to be sure no one else in the class has selected the same
topic. Your request should be brief but include
the name of the hemoglobin variant, the nature of the mutation, at
least two literature citations to relvant references, and
any medical consequences of the condition. Selections should
be made on or before the second Friday in April after Spring Break.
HbC and HbS
are not available.
Hemoglobin variants taken as of 3:00 PM, 28 April 2008. Student
initials after variant.
Return to Hal
White's Home Page, Course Home Page,
or Departmental Home Page.
updated: 13 May 2008
by Hal White [halwhite at udel.edu]
2008 Harold B. White, Department of Chemistry and Biochemistry,
University of Delaware