1. Chemistry and Biology Interface Summer Institute – Sept. 11, 2011

2. 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

3. Learning Goals of Teachable Unit- Students will: Understand the Process of Science Appreciate underlying chemistry of biological molecules Understand connection between hierarchical levels of organization Understand how structure affects function

4. 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

5. Proteins Today’s topics Proteins and health – food and you Other Health issues Protein structure and function

6. Review-1⁰  4 ⁰ Structure of a Protein http://www.rci.rutgers.edu/~uzwiak/AnatPhys/APFallLect2.html

7. What does soda have to do with proteins? Have you noticed this warning before? Where?

8. What does diet soda have to do with proteins? Have you noticed this warning before?

9. Which one of the following structures is phenylalanine? a) b)c)d)

10. 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

11. Worldwide distribution of PKU 1/10,000 1/9,000 1/100,000 1/2,600

12. How does diet soda play into all of this? - + 3 - + 3 - - + 3 Aspartame  aspartic acid + phenylalanine

13. What kind of bond or interaction is being broken in this reaction? a) hydrogen b) ionic c) covalent bond d) non-covalent interaction - + 3 - + 3 - - + 3 Aspartame  aspartic acid + phenylalanine

14. 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

16. phenylalanine mental retardation high levels of cell toxin stunted growth poor muscle tone white skin, hair, light colored eyes - + 3 Consequences of Elevated Phenylalanine melanin pigments PAH tyrosine hormone production

17. Brainstorm ! What can baby X’s parents do to manage this disease (ie. why is there a warning on diet soda?)

18. 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 ?

22. 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.)