Chapter 1: Amino Acids, Peptides, and Proteins
🎯 Diagnostic: Test Your Starting Level 24 questions (2 per section). No prior reading required - see what you already know.
Aim to answer every question before checking. Missed questions point you to the sections you need most.
1. (1.1) How many distinct substituents are attached to the alpha carbon of a standard chiral amino acid?
C. The alpha carbon bonds to four different groups: amino (-NH2), carboxyl (-COOH), hydrogen, and R group. Four different substituents is what makes it a chiral center.
2. (1.1) Which of the 20 standard amino acids lacks chirality?
A. Glycine's R group is a single hydrogen, so its alpha carbon has only three unique substituents (two hydrogens plus amino and carboxyl). All other standard amino acids are chiral.
3. (1.2) Which category best describes the side chain of valine?
B. Valine has a branched hydrocarbon side chain (isopropyl). Aliphatic, nonpolar, hydrophobic - it buries in the protein core.
4. (1.2) Which pair are both BASIC amino acids?
D. Lysine, Arginine, and Histidine are the three basic amino acids (positive at physiological pH). Asp/Glu are acidic (A), Ser/Thr are polar uncharged (B), Phe/Trp are aromatic/nonpolar (C).
5. (1.3) Which amino acid forms disulfide bridges?
B. Two cysteines oxidize to form a covalent S-S (disulfide) bridge. Methionine also contains sulfur but its sulfur is part of a thioether and does not form disulfide bonds.
6. (1.3) Proline is unique among standard amino acids because:
A. Proline's side chain connects back to its own amino nitrogen, forming a 5-membered ring. This "locked" structure disrupts alpha helices and introduces kinks - proline is called the "helix breaker."
7. (1.4) At physiological pH (~7.4), an amino acid with no ionizable side chain exists predominantly as a:
C. At pH 7.4, the carboxyl (pKa ~2) is deprotonated (-COO-) and the amino group (pKa ~9) is protonated (-NH3+). Net charge = 0, but the molecule carries both charges - the zwitterion form.
8. (1.4) For a neutral amino acid (no charged side chain), the isoelectric point (pI) equals:
D. pI is calculated as the mean of the two pKa values on either side of the zwitterion. For glycine: pI = (2.3 + 9.6)/2 ≈ 5.95.
9. (1.5) Peptide bond formation between two amino acids is a:
B. The carboxyl of one amino acid attacks the amino group of the next, releasing H2O. This condensation forms an amide (peptide) bond. Requires the ribosome and is energetically uphill in solution alone.
10. (1.5) Which enzyme specifically cleaves peptide bonds on the C-terminal side of lysine or arginine residues?
A. Trypsin cleaves after positively charged residues (Arg, Lys). Chymotrypsin cleaves after bulky aromatic residues (Phe, Trp, Tyr). Memorize this pair - it shows up in sequencing questions.
11. (1.6) The peptide bond is planar because:
C. The nitrogen lone pair delocalizes into the adjacent C=O. This gives the C-N bond ~40% double-bond character, locking the six atoms around the peptide bond into a plane. Phi and psi angles (around the flanking alpha carbons) are what actually rotate.
12. (1.6) In the peptide backbone, the rotatable dihedral angles are called:
B. Phi (φ) is rotation around N-Cα; psi (ψ) is rotation around Cα-C(=O). The peptide bond itself (omega, ω) is locked near 180°. A Ramachandran plot maps allowed phi/psi combinations.
13. (1.7) Primary structure refers to:
A. Primary structure is the amino acid sequence, read N-terminus to C-terminus. It is held together by covalent peptide bonds and is what the DNA code directly encodes.
14. (1.7) In the sickle cell mutation, the amino acid at position 6 of the hemoglobin beta chain changes from glutamate to valine. Which level of protein structure is directly altered by this substitution?
D. Primary structure IS the sequence, so changing one amino acid is a primary-structure change. The downstream consequences cascade through tertiary and quaternary levels (polymerization into sickle fibers), but the direct change is to the primary sequence.
15. (1.8) Alpha helices are stabilized by hydrogen bonds between:
C. The alpha helix's hallmark hydrogen bond is backbone-to-backbone: C=O of residue n pairs with N-H of residue n+4. Side chains project outward and are NOT what stabilize the helix.
16. (1.8) Which amino acid is most likely to disrupt an alpha helix if inserted mid-strand?
B. Proline's rigid ring locks its phi angle and its backbone nitrogen has no hydrogen to donate for the helical hydrogen bond. Proline is the classic "helix breaker."
17. (1.9) The dominant force driving formation of tertiary structure in globular proteins is:
A. The hydrophobic effect is the main driver because it involves every nonpolar residue. It is entropy-driven: water forced to order itself around exposed nonpolar surfaces is released to bulk when those residues get buried.
18. (1.9) Per single bond, the strongest interaction stabilizing tertiary structure is:
D. The disulfide bond is covalent (~60 kcal/mol) while the others are noncovalent (a few kcal/mol each). "Strongest per bond" is distinct from "most important overall" - the hydrophobic effect dominates overall because of sheer numbers.
19. (1.10) Quaternary structure refers to:
B. Quaternary structure exists ONLY in proteins that have more than one polypeptide chain. Hemoglobin (α2β2) has quaternary structure; myoglobin (single chain) does not.
20. (1.10) Which protein has quaternary structure?
C. Hemoglobin is a heterotetramer of two alpha and two beta chains - textbook quaternary structure. Myoglobin is a single chain (no quaternary structure), and ribonuclease A is monomeric.
21. (1.11) The hydrophobic effect is best explained by:
A. Water ordered around exposed nonpolar surfaces has low entropy. Burying those surfaces releases water back into disordered bulk, increasing system entropy. Favorable ΔS is what makes folding thermodynamically spontaneous.
22. (1.11) Which treatment denatures a protein by reducing disulfide bonds?
D. β-mercaptoethanol and DTT are reducing agents - they donate electrons to break the S-S bond back into two -SH groups. Urea and heat break noncovalent interactions but leave disulfides intact.
23. (1.12) Hemoglobin is classified as a:
C. Hemoglobin contains four heme prosthetic groups, each with a central iron (Fe2+) atom that binds O2. Heme is the non-peptide "prosthetic" component; the protein is globin.
24. (1.12) A glycoprotein is a conjugated protein that:
B. Glycoproteins have oligosaccharides covalently attached (N- or O-linked). Examples: antibodies, mucins, most cell-surface receptors. Lipoproteins (C) carry lipids; nucleoproteins (A) bind nucleic acids (e.g., histones).
Fry an egg. Watch the translucent goo turn opaque white in seconds. You just ran a biochemistry experiment at home. The clear “goo” is a solution of protein molecules (mostly albumin) folded into precise 3D shapes. Heat unravels those shapes. The proteins tangle, light scatters, the egg turns white. That is denaturation. You cannot unfry it.
Or consider sickle cell disease. A single amino acid swap (glutamate to valine) in a chain of 146 amino acids warps red blood cells into rigid crescents that clog capillaries. One letter. One molecule. A whole disease. That is how profoundly the amino acid sequence controls function.
This chapter covers the building blocks (amino acids), the bond that links them (the peptide bond), and the four levels of folding that turn a linear chain into a working machine. Get this chapter right and the rest of biochemistry will make sense, because proteins are the machines that carry out almost everything you study in the next 11 chapters.
Proteins are Folded Paper
Here is the mental model for this whole chapter. A protein is a sheet of paper. The printed letters are the amino acid sequence (the primary structure). The folds you make in the paper turn it into an origami crane, a boat, or a frog. Same paper, same letters, different shapes, completely different objects.
Change the order of the letters and the paper folds into something else. Make one wrong fold and you get a useless blob. The sequence determines the shape, and the shape determines the function. Memorize that one sentence and everything else in this chapter is a detail.
In This Chapter
- 1.1 Amino Acid Structure
- 1.2 Classification of Amino Acids
- 1.3 The 20 Standard Amino Acids
- 1.4 Acid-Base Chemistry of Amino Acids
- 1.5 Peptide Bond Formation
- 1.6 Peptide Bond Properties
- 1.7 Primary Structure
- 1.8 Secondary Structure
- 1.9 Tertiary Structure
- 1.10 Quaternary Structure
- 1.11 Protein Folding and Denaturation
- 1.12 Conjugated Proteins
- Section Test