1. The Structure and Function of Macromolecules Part II: Proteins & Nucleic Acids
A fair amount of this material will be new to students with the possible exception of the DNA-related material. Although some of this material is not directly tied to the framework, it is still fundamental to the understanding of the structure and function of proteins and nucleic acids as they relate to evolutionary mechanisms.
Big Idea 2, EK 2.A.3: Organisms must exchange matter with the environment to grow, reproduce and maintain organization. a) Molecules and atoms from the environment are necessary to build new molecules. Evidence of student learning is a demonstrated understanding of each of the following: 1. Carbon moves from the environment to organisms where it is used to build carbohydrates, proteins, lipids for nucleic acids. Carbon is used in storage compounds and cell formation in all organisms.

2. The FOUR Classes of Large Biomolecules
All living things are made up of four classes of large biological molecules:
Carbohydrates
Lipids
Protein
Nucleic Acids
Macromolecules are large molecules composed of thousands of covalently bonded atoms
Molecular structure and function are inseparable
This lesson will deal with protein and nucleic acids. Emphasize yet again that within the molecule, the intramolecular forces are covalent bonds, but the intermolecular forces (IMFs) between molecules will vary due to the polarity of the molecule as a whole.

3. Proteins Come In Many Varieties!
Proteins include a diversity of structures, resulting in a wide range of functions
Proteins account for more than 50% of the dry mass of most cells
Protein functions include structural support, storage, transport, cellular communications, movement, and defense against foreign substances
Ask students what they already know about proteins and protein synthesis. Hopefully, they remember a few things from Biology I.

4. Enzymatic Enzymatic proteins Enzyme
Function: Selective acceleration of chemical reactions
Example: Digestive enzymes catalyze the hydrolysis of bonds in food molecules.
Emphasize the specificity of enzymes. Also emphasize the catalytic nature of enzymes and that they function best in a unique set of pH and temperature conditions. Why is that? It is due to the shape of the enzyme molecule. That shape is held in place by IMFs and/or covalent or ionic bonding. Changes in pH or temperature often disrupt the electrostatic forces that are responsible for an enzyme’s specific shape.
Enzyme

5. Storage Storage proteins Amino acids for embryo Ovalbumin
Function: Storage of amino acids
Examples: Casein, the protein of milk, is the major source of amino acids for baby mammals. Plants have storage proteins in their seeds. Ovalbumin is the protein of egg white, used as an amino acid source for the developing embryo.
Ask students to identify other food sources that are proteins. One of my favorite quotes ever is from Bob Harper, a personal trainer from The Biggest Loser. Simply put, “If the food in question had a mother, then it’s a protein!”
Amino acids for embryo
Ovalbumin

6. Hormonal Hormonal proteins Insulin secreted High blood sugar
Function: Coordination of an organism’s activities
Example: Insulin, a hormone secreted by the pancreas, causes other tissues to take up glucose, thus regulating blood sugar concentration
Ask students to give examples of hormonal proteins. They should easily come up with testosterone and estrogen among others.
Insulin secreted
High blood sugar
Normal blood sugar

7. Defensive Defensive proteins Antibodies Virus Bacterium
Function: Protection against disease
Example: Antibodies inactivate and help destroy viruses and bacteria.
Antibodies
Ask students which body system utilizes these types of proteins.
Virus
Bacterium

8. Transport Transport proteins Transport protein Cell membrane
Function: Transport of substances
Examples: Hemoglobin, the iron-containing protein of vertebrate blood, transports oxygen from the lungs to other parts of the body. Other proteins transport molecules across cell membranes.
Transport protein
Ask which body system utilizes hemoglobin.
Cell membrane

9. Receptor Receptor proteins
Function: Response of cell to chemical stimuli
Example: Receptors built into the membrane of a nerve cell detect signaling molecules released by other nerve cells.
Receptor protein
Ask if they know any of the “signaling molecules” as well as which body system is involved in this process. Hopefully, they come up with the nervous system, the fight or flight response as it relates to adrenaline, etc.
Signaling molecules

10. Structural Structural proteins Collagen Connective tissue 60 m
Function: Support
Examples: Keratin is the protein of hair, horns, feathers, and other skin appendages. Insects and spiders use silk fibers to make their cocoons and webs, respectively. Collagen and elastin proteins provide a fibrous framework in animal connective tissues.
Emphasize collagen’s role in the aging process and it’s unfortunate consequences such as wrinkling!
Collagen
Connective tissue
60 m

11. More About Enzymes
Enzymes are a type of protein that acts as a catalyst to speed up chemical reactions
Enzymes can perform their functions repeatedly, functioning as workhorses that carry out the processes of life
This is a perfect time to bring out the “water noodle” enzyme models. You can extend this portion of the lesson to include competitive inhibition, etc.

12. Amino Acids: Yet Another Monomer
Side chain (R group)
Amino acids are organic molecules with carboxyl and amino groups
Amino acids differ in their properties due to differing side chains, called R groups
 carbon
There are 23 amino acids (aa’s) but only 20 are biologically active.
Amino group
Carboxyl group

13. Polypeptides
Polypeptides are unbranched polymers built from the same set of 20 amino acids
A protein is a biologically functional molecule that consists of one or more polypeptides
Ask, how many peptide bonds are formed. Ask how many amino acids are in this polypeptide. Additionally, emphasize the arrangement of the aa’s in this diagram. If one of the aa’s is “flipped” along the horizontal axis, it’s amine group no longer aligns with the neighboring aa’s carboxylic acid group, thus no dehydration reaction can occur.

14. Hydrophobic: Therefore retreat from water!
Nonpolar side chains; hydrophobic
Side chain
Glycine (Gly or G)
Alanine (Ala or A)
Valine (Val or V)
Leucine (Leu or L)
Isoleucine (Ile or I)
Absolutely no need to memorize these, but there is a need to recognize WHY these retreat from water. Point out that these “R” groups are very nonpolar as evidenced by the “hydrocarbonish” or CHX nature of the elements involved in the R groups.
Methionine (Met or M)
Phenylalanine (Phe or F)
Tryptophan (Trp or W)
Proline (Pro or P)

15. Hydrophilic: Therefore Are Attracted to Water
Absolutely no need to memorize these, but emphasize that while these R groups also look “hydrocarbonish”, that there are unpaired electrons left off this diagram. Each N, O or S atom has unshared electron pairs that make them polar and water soluble.

16. Hydrophilic: But Electrically Charged!
Again, no need to memorize these but students should know that ammonia (NH3) is a weak base from Chemistry I. Remove an H from ammonia and you have its “cousin” the amine group which is also basic.

17. Peptide Bonds Amino acids are linked by peptide bonds
A polypeptide is a polymer of amino acids
Polypeptides range in length from a few to more than a thousand monomers (Yikes!)
Each polypeptide has a unique linear sequence of amino acids, with a carboxyl end (C-terminus) and an amino end (N-terminus)
Emphasize that the peptide bond forms as a consequence of a dehydration synthesis reaction.

18. Peptide Bonds

19. Peptide Bonds

20. Protein Structure & Function
At first, all we have is a string of AA’s bound with peptide bonds.
Once the string of AA’s interacts with itself and its environment (often aqueous), then we have a functional protein that consists of one or more polypeptides precisely twisted, folded, and coiled into a unique shape
The sequence of amino acids determines a protein’s three-dimensional structure
A protein’s structure determines its function

21. Protein Structure: 4 Levels
Primary structure consists of its unique sequence of amino acids
Secondary structure, found in most proteins, consists of coils and folds in the polypeptide chain
Tertiary structure is determined by interactions among various side chains (R groups)
Quaternary structure results when a protein consists of multiple polypeptide chains
Now is the time to explain that a string of aa’s is a polypeptide and NOT yet a protein. The protein forms once the secondary, tertiary and quaternary structures are established and that is usually facilitated in an aqueous environment. Also emphasize that “conformation” is the “big people” word for shape and that if the conformation changes, the function of the protein is affected.

22. Primary Structure
Primary structure, the sequence of amino acids in a protein, is like the order of letters in a long word
Primary structure is determined by inherited genetic information
Keep it simple. Explain to students that when they were about 3 years old, they would sing the alphabet song to anyone that would listen! They had no idea that one day they’d use that to spell or that they would use it to read, or write sentences, or paragraphs or research papers!
Also, remind them yet again that they have some prior knowledge regarding DNA and the process of protein synthesis.

23. Secondary Structure
The coils and folds of secondary structure result from hydrogen bonds between repeating constituents of the polypeptide backbone
Typical secondary structures are a coil called an  helix and a folded structure called a  pleated sheet
Emphasize yet again that a H-bond is NOT a bonded H! It’s an IMF, not a covalent bond, but rather an electrostatic force. H-bonds are fragile and easily interrupted by pH or temperature changes.

24. Secondary Structure
Linus Pauling is my favorite scientist, so I’d have to share that he won his first Nobel Prize in Chemistry in 1954  "for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances". Those complex substances are proteins and he figured out the  helix and a folded structure called a  pleated sheet! Students may know that the electronegativity scale they learned in Chemistry I is the “Pauling Electronegativity Scale”. But, they may not know that he was hot on the heels of beating Watson & Crick to the “discovery” of the structure of DNA OR that he also won a Nobel Prize for Peace. Whew!

25. Tertiary Structure
Tertiary structure is determined by interactions between R groups, rather than interactions between backbone constituents
These interactions between R groups include actual ionic bonds and strong covalent bonds called disulfide bridges which may reinforce the protein’s structure.
IMFs such as London dispersion forces (LDFs a.k.a. and van der Waals interactions), hydrogen bonds (IMFs), and hydrophobic interactions (IMFs) may affect the protein’s structure
Here we go again, the second bullet refers to actual chemical bonds—the sharing of a pair of electrons. The third bullet refers to intermolecular forces (IMFs) with LDFs that the biology books often refer to as van der Waals forces or interactions. H-bonds are a special case of dipole-dipole interactions. While none of these distinctions will be asked on the AP Biology exam, they certainly will on the AP Chemistry exam and should be taught in Chem I as well. It’s not surprising that students are confused since the vocabulary is so different from book to book! Ugh!

26. Tertiary Structure
Revisit the “curly hair” example for disulfide bridges. Folks with curly hair have more disulfide bridges and we often use heat to alter them 1.Use a hair dryer-brush-mechanically pull on the hair while applying heat to disrupt the S-S bridges. 2. Flat irons on dry hair 3. “Perms”—A basic solution that reeks of ammonia (a base, thus a pH rather than thermal approach) is applied to hair that has been wound onto skinny curlers and left to sit for about 20 minutes to allow S-S to form.

27. Quaternary Structure
Quaternary structure results when two or more polypeptide chains form one macromolecule
Collagen is a fibrous protein consisting of three polypeptides coiled like a rope
Emphasize that Quaternary structure involves a collection of polypeptides brought together into a new conformation.

28. Quaternary Structure
Hemoglobin is a globular protein consisting of four polypeptides: two alpha and two beta chains
The classic example!

29. Four Levels of Protein Structure Revisited
A nice visual summary!

30. Sickle-Cell Disease: A change in Primary Structure
A slight change in primary structure can affect a protein’s structure and ability to function
Sickle-cell disease, an inherited blood disorder, results from a single amino acid substitution in the protein hemoglobin
A perfect practical example of how a change in protein structure affects function. Be sensitive to the fact that you may have a student that suffers from sickle-cell disease.
“Normal” Red Blood Cells

31. Sickle-Cell Disease: A change in Primary Structure
A slight change in primary structure can affect a protein’s structure and ability to function
Sickle-cell disease, an inherited blood disorder, results from a single amino acid substitution in the protein hemoglobin
The sickled cells cannot move the blood vessels as effectively and can obstruct capillaries and restrict blood flow to an organ, resulting in pain, necrosis and often organ damage. Ask if students studied the connection between sickle-cell trait and malaria in Biology I.

32. Sickle-Cell Disease: A change in Primary Structure

33. What Determines Protein Structure?
In addition to primary structure, physical and chemical conditions can affect structure
Alterations in pH, salt concentration, temperature, or other environmental factors can cause a protein to unravel
This loss of a protein’s native structure is called denaturation
A denatured protein is biologically inactive
Ask how EACH of the items mentioned could disrupt protein structure.

34. Denature: Break Bonds or Disrupt IMFs
This concept is an energy concept as well. If thermal energy is added, the molecules vibrate more vigorously. At some point the electrostatic attractions (H-bonds) are overcome and “let go”.
When students write free-responses, make sure they define terms they use within their writing. “A change in temperature denatures a protein since the H-bonds (or IMFs) are disrupted (or overcome, or altered, or anything else that implies the structure is broken down).” Lots of ways to wordsmith the response correctly!

35. Nucleic Acids
Nucleic acids store, transmit, and help express hereditary information
The amino acid sequence of a polypeptide is programmed by a unit of inheritance called a gene
Genes are made of DNA, a nucleic acid made of monomers called nucleotides
Ask questions to see what they already know about DNA structure. A good deal of this should be prior knowledge!

36. Two Types of Nucleic Acids
There are two types of nucleic acids
Deoxyribonucleic acid (DNA)
Ribonucleic acid (RNA)
DNA provides directions for its own replication
DNA directs synthesis of messenger RNA (mRNA) and, through mRNA, controls protein synthesis
Protein synthesis occurs on ribosomes
Pause and let student examine both structures. WHERE exactly is the “deoxy” part of the name coming from?

37. DNA 1 Synthesis of mRNA mRNA NUCLEUS CYTOPLASM Figure 5.25-1
DNA → mRNA

38. Movement of mRNA into cytoplasm
Figure
DNA 1
Synthesis of mRNA
mRNA
NUCLEUS
CYTOPLASM
mRNA 2
Movement of mRNA into cytoplasm
DNA →m RNA → what next?? (ribosome!)

39. Movement of mRNA into cytoplasm Ribosome
Figure
DNA 1
Synthesis of mRNA
mRNA
NUCLEUS
CYTOPLASM
mRNA 2
Movement of mRNA into cytoplasm
Ribosome
DNA → mRNA → ribosome →protein. What’s missing? See if they can supply the details about tRNA, etc. Try to connect to what they already know and correct any misconceptions. 3
Synthesis of protein
Amino acids
Polypeptide

40. The Components of Nucleic Acids
Each nucleic acid is made of monomers called nucleotides
Each nucleotide consists of a nitrogenous base, a pentose sugar, and one or more phosphate groups
Again, most likely prior knowledge.

41. Nitrogenous base Phosphate group Sugar (pentose)
Figure 5.26ab
Sugar-phosphate backbone
5 end
5C
3C
Nucleoside
Nitrogenous base
5C
1C
Components of nucleic acids.
Phosphate group
3C
Sugar (pentose)
5C
3C
(b) Nucleotide
3 end
(a) Polynucleotide, or nucleic acid

42. (c) Nucleoside components
Figure 5.26c
Nitrogenous bases
Pyrimidines
Cytosine (C)
Thymine (T, in DNA)
Uracil (U, in RNA)
Sugars
Purines
Ask about base pairing. Students most likely know A-T and G-C. Emphasize that the pairing is due to, you guessed it, H-bonding!
Deoxyribose (in DNA)
Ribose (in RNA)
Adenine (A)
Guanine (G)
(c) Nucleoside components

43. Ask about base pairing. Students most likely know A-T and G-C
Ask about base pairing. Students most likely know A-T and G-C. Emphasize that the pairing is due to, you guessed it, H-bonding! Note the formation of 2 H-bonds for AT and 3 H-bonds for GC. No need to memorize, just interesting to the student that makes you crazy with “But, why?” questions.

44. The Devil is in the Details
There are two families of nitrogenous bases
Pyrimidines (cytosine, thymine, and uracil) have a single six-membered ring
Purines (adenine and guanine) have a six-membered ring fused to a five-membered ring
In DNA, the sugar is deoxyribose; in RNA, the sugar is ribose
No need to memorize the 5 vs. 6 membered ring distinction.

45. The Devil is in the Details
Adjacent nucleotides are joined by covalent bonds that form between the —OH group on the 3 carbon of one nucleotide and the phosphate on the 5 carbon on the next
These links create a backbone of sugar-phosphate units with nitrogenous bases as appendages
The sequence of bases along a DNA or mRNA polymer is unique for each gene
Emphasize the “backbone of the ladder” is held together with actual covalent bonds (much stronger than an IMF). We number C’s in a ring starting with the O and going clockwise if anyone asks.

46. The Devil is in the Details
RNA molecules usually exist as single polypeptide chains
DNA molecules have two polynucleotides spiraling around an imaginary axis, forming a double helix
In the DNA double helix, the two backbones run in opposite 5→ 3 directions from each other, an arrangement referred to as antiparallel
One DNA molecule includes many genes
Details they probably didn’t get in Biology I.

47. The Devil is in the Details
The nitrogenous bases in DNA pair up and form hydrogen bonds: adenine (A) always with thymine (T), and guanine (G) always with cytosine (C)
Called complementary base pairing
Complementary pairing can also occur between two RNA molecules or between parts of the same molecule
In RNA, thymine is replaced by uracil (U) so A and U pair
Probably prior knowledge.

48. Base pair joined by hydrogen bonding5 3
Sugar-phosphate backbones
Hydrogen bonds
Base pair joined by hydrogen bonding
The single dotted line between base pairs is an oversimplification! Reiterate the sugar-phosphate backbones or sides of the ladder are held together with actual covalent chemical bonds. The rungs of the ladder or base pairs align the way they do because of H-bonding (an IMF) AND therefore are not as tightly held together. The elegance involves the ease of the “unzipping” or “zipping” of the molecule vs. the stability of the single strand when it is unzipped, thus vulnerable to damage.
Base pair joined by hydrogen bonding 3 5
(a) DNA
(b) Transfer RNA

49. Link to Evolution
The linear sequences of nucleotides in DNA molecules are passed from parents to offspring
Two closely related species are more similar in DNA than are more distantly related species
Molecular biology can be used to assess evolutionary kinship
Link “Big Ideas” together as often as possible!

50. Could Prove Useful
The “type of linkage” is not nearly as important as the rest of this summary. Student still have to be able to read and interpret test questions!

51. Created by:
René McCormick
National Math and Science
Dallas, TX