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 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

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 youOther 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)

+H3N CH C

CH2

O-

O

N

NN

N

NH2

O

HOH

HH

HH

HO

CHO

OHH

HHO

OHH

OHH

CH2OH

What do you think Phenylketonuria (PKU) is?

a) Diet soda addictionb) Vitamin deficiencyc) A toxind) A plant based flavoringe) Human metabolic disorder

Worldwide distribution of PKU

1/10,000

1/9,000

1/100,000

1/2,600

How does diet soda play into all of this?

- +3

-

+3

-- +

3

Aspartame 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

- +3

-

+3

-- +

3

Aspartame aspartic acid + phenylalanine

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

phenylalanine

mental retardationhigh levels of cell toxin

stunted growthpoor muscle tone

white skin, hair,light colored eyes

-

+3

Consequences of Elevated Phenylalanine

melanin pigments

PAH tyrosine

hormoneproduction

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 arosein 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.)