Chemistry and Biology Interface
Summer Institute – Sept. 11, 2011
Teachable Unit
• Title: Proteins
Context
• A one-week series in a 100-level course for
biology majors given early in the semester
• Class is 50-100 students
Learning Goals of Teachable UnitStudents will:
• Understand the Process of Science
• Appreciate underlying chemistry of biological
molecules
• Understand connection between hierarchical
levels of organization
• Understand how structure affects function
Learning Outcomes – Students can:
• Define ionic & covalent bonds, noncovalent interactions
• Compare/contrast the strengths of covalent &
noncovalent interactions
• Classify types of chemical interactions contributing to
different levels of protein structure
• Draw peptide bonds, given two or more amino acids
• Explain a medical condition associated with a change in
protein structure* (today’s Teachable tidbit)
• Formulate a hypothesis about a protein’s function based
on its structure
Proteins
• Today’s topics
• Proteins and health
– food and you
Other Health issues
• Protein structure and function
Review-1⁰  4 ⁰ Structure of a Protein
http://www.rci.rutgers.edu/~uzwiak/AnatPhys/APFallLect2.html
What does soda have to do with proteins?
Have you noticed this
warning before?
Where?
What does diet soda have to do with proteins?
Have you noticed this
warning before?
Which one of the following structures is phenylalanine?
a)
b)
c)
d)
What do you think Phenylketonuria (PKU) is?
a) Diet soda addiction
b) Vitamin deficiency
c) A toxin
d) A plant based flavoring
e) Human metabolic disorder
Worldwide distribution of PKU
1/9,000
1/100,000
1/10,000
1/2,600
How does diet soda play into all of this?
-
-
Aspartame
-
+
3

+
3
+
3
aspartic acid
+
phenylalanine
-
-
Aspartame
-
+
3

+
3
+
3
aspartic acid
+
phenylalanine
What kind of bond or interaction is being broken in this reaction?
a) hydrogen
b) ionic
c) covalent bond
d) non-covalent interaction
Case Study
• The X family’s second child was born in 1955. The mother had a healthy
pregnancy before the baby’s birth. Their child (baby X) appears to be born
healthy though with noticeably lighter complexion than its parents and
older sibling.
• It is quite a surprise to the X family that a few days after the baby’s birth,
the baby starts to be very lethargic, is not eating well, and has a strange
“mousy” odor that is noticeable in their wet diaper. The X family decides
to take their baby back to the hospital for tests.
• A blood test reveals that their child has an inherited disorder called
Phenylketonuria (PKU). Due to a genetic mutation, Baby X is unable to
make phenylalanine hydroxylase (PAH), which is the enzyme responsible
for metabolizing phenylalanine, as shown in the diagram below.
• 5 minutes to answer Questions 1 and 2-- and then we’ll discuss
Consequences of Elevated
Phenylalanine
high levels
of cell toxin
mental retardation
white skin, hair,
light colored eyes
melanin pigments
+
3
phenylalanine
PAH
tyrosine
hormone
production
stunted growth
poor muscle tone
Brainstorm !
• What can baby X’s parents do to manage this
disease (ie. why is there a warning on diet soda?)
Exit question
• If alanine had instead been replaced by valine,
please suggest how this difference might
affect the structure of the PAH enzyme
compared to the mutation suffered by baby X?
• Could this influence the functionality of the
PAH enzyme ?
FIGURE 1. Human history hypothesized from the viewpoint of allelic diversity at the human phenylalanine hydroxylase (PAH)
gene locus. Following an ‘‘out of Africa’’ range expansion and divergence, di¡erent sets of phenylketonuria-causing alleles arose
in Europeans (Caucasians) and Asian Orientals.Their distribution re£ects various forces of evolution including genetic drift
(and perhaps natural selection). Drift with a founder e¡ect (open circles) is the likely explanation for the relative rarity of pathogenic PAH
alleles in American aboriginals, Ashkenazi, Finnish, and Japanese populations (also in Polynesians). Demic expansion, migration, and gene
£ow disrupted trees of descent in preand post-Neolithic eras (10,000 ybp). European range expansion, and the creation of neo-European
populations overseas during the recent millennium, explain redistribution of certain PAH alleles from their European sources. (Taken from
Donlon et al. [2004] Donlon J, Levy H, Scriver CR. 2004. Hyperphenylalaninemia: phenylalanine hydroxylase deficiency. In: Scriver CR,
Beaudet AL, Sly SW, Valle D, associate editors. Childs B, Kinzler KW, Vogelstein B, editors. The metabolic and molecular bases of inherited
disease. New York: McGraw-Hill.)