2. PROTEINS

Question 1 Why are proteins considered the most functionally diverse macromolecules in the human body?

Because they participate in virtually every biological process, serving structural, catalytic, transport, regulatory, contractile, immune, and signaling functions.

Question 2 What common structural feature is shared by all proteins despite their diverse functions?

They are linear polymers composed of amino acids joined by peptide bonds.

Question 3 How many standard amino acids are incorporated into mammalian proteins?

Twenty standard amino acids.

Question 4 Why are only twenty amino acids considered standard amino acids?

Because they are directly encoded by DNA during protein synthesis.

Question 5 Name the four components attached to the α-carbon of a standard amino acid.

An amino group, a carboxyl group, a hydrogen atom, and a unique side chain (R group).

Question 6 Which component of an amino acid primarily determines its chemical behavior and biological function?

The side chain (R group).

Question 7 Why is the R group considered the most important determinant of protein function?

Because it determines the amino acid's size, polarity, charge, hydrophobicity, and ability to interact with other molecules.

Question 8 What is unique about the amino group of proline compared with all other standard amino acids?

Proline contains a secondary amino group that forms part of a rigid ring structure.

Question 9 At physiologic pH, what is the charge of the amino group of a free amino acid?

Positively charged (NH₃⁺).

Question 10 At physiologic pH, what is the charge of the carboxyl group of a free amino acid?

Negatively charged (COO⁻).

Question 11 Why do free amino acids predominantly exist as zwitterions at physiologic pH?

Because the amino group is protonated while the carboxyl group is deprotonated, giving the molecule both a positive and a negative charge simultaneously.

Question 12 Define an amphoteric molecule.

A molecule capable of acting as either an acid or a base depending on its environment.

Question 13 Why are amino acids considered amphoteric compounds?

Because they contain both an acidic carboxyl group and a basic amino group that can donate or accept protons.

Question 14 Explain why amino acids within proteins are less chemically reactive than free amino acids.

Because most amino and carboxyl groups become involved in peptide bond formation, leaving the side chains responsible for most chemical interactions.

Question 15 How are amino acids primarily classified in biochemistry?

According to the chemical properties of their side chains, especially polarity and charge.

Question 16 What is meant by a nonpolar amino acid?

An amino acid whose side chain lacks significant charge or polarity and interacts poorly with water.

Question 17 What is meant by a polar amino acid?

An amino acid whose side chain contains electronegative atoms that can interact with water through dipole interactions or hydrogen bonding.

Question 18 Why are nonpolar amino acids generally buried within soluble globular proteins?

To minimize contact between their hydrophobic side chains and the surrounding aqueous environment.

Question 19 Why are polar amino acids commonly located on the surface of soluble proteins?

Because they interact favorably with water through hydrogen bonding and electrostatic interactions.

Question 20 Predict what would likely happen to the stability of a soluble protein if several hydrophobic core amino acids were replaced by charged amino acids.

Protein stability would decrease because disruption of the hydrophobic core interferes with proper folding and weakens the tertiary structure.

Question 21 Why are amino acids commonly classified according to their side chains rather than their backbone groups?

Because the side chain determines most of the amino acid’s chemical behavior and its role in protein structure.

Question 22 What property do nonpolar amino acid side chains share?

They are hydrophobic and tend to avoid water.

Question 23 Where are nonpolar amino acids usually found in soluble proteins?

Buried in the interior of the protein core.

Question 24 Where are nonpolar amino acids usually found in membrane proteins?

On the outer surface interacting with the hydrophobic lipid environment.

Question 25 Why is glycine considered a special amino acid?

Because it is the smallest amino acid and its α-carbon is not chiral.

Question 26 Why is proline considered unusual among amino acids?

Because its side chain forms a rigid ring with the amino nitrogen, giving it a secondary amino group and disrupting α-helices.

Question 27 What effect does proline have on globular protein secondary structure?

It interrupts α-helices.

Question 28 Why is cysteine biochemically important?

Because its sulfhydryl group can form disulfide bonds that stabilize protein structure.

Question 29 What is cystine?

Two cysteine residues linked by a disulfide bond.

Question 30 What is the major importance of histidine in proteins?

Its side chain can ionize near physiologic pH, allowing it to act in buffering and enzyme active sites.

Question 31 Why is histidine especially useful in hemoglobin?

Because it contributes to hemoglobin’s buffering role by accepting or donating protons.

Question 32 Which amino acids are acidic at physiologic pH?

Aspartic acid and glutamic acid.

Question 33 What are the ionized forms of aspartic acid and glutamic acid called?

Aspartate and glutamate.

Question 34 Which amino acids are basic at physiologic pH?

Lysine, arginine, and histidine.

Question 35 Which basic amino acid is usually largely uncharged at physiologic pH in free form?

Histidine.

Question 36 Which amino acids are aromatic and important for UV absorption?

Phenylalanine, tyrosine, and tryptophan.

Question 37 Which amino acid has a phenolic hydroxyl group that can participate in hydrogen bonding and can be phosphorylated?

Tyrosine.

Question 38 Which amino acids are commonly listed as essential in the slide summary?

Histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine.

Question 39 What does “conditionally essential” mean?

The amino acid is usually synthesized by the body but may become necessary in the diet during stress, growth, or illness.

Question 40 Why is methionine biochemically important beyond being an amino acid?

Because it is a precursor of S-adenosylmethionine, a major methyl-group donor.

Question 41 Why is glycine the only amino acid that is not optically active?

Because its α-carbon is bonded to two hydrogen atoms, making it achiral.

Question 42 What structural feature makes most amino acids chiral?

Their α-carbon is attached to four different groups.

Question 43 Define enantiomers.

Enantiomers are stereoisomers that are nonsuperimposable mirror images of each other.

Question 44 What are the two stereochemical configurations of amino acids?

D- and L-configurations.

Question 45 Which amino acid configuration is incorporated into mammalian proteins?

L-amino acids.

Question 46 Where are D-amino acids commonly found?

In bacterial cell walls and certain antibiotics.

Question 47 Why is glycine frequently found in tight turns of proteins?

Because its small size provides greater conformational flexibility.

Question 48 Predict the effect of replacing glycine with valine in a region requiring flexibility.

Flexibility would decrease because valine has a larger hydrophobic side chain that restricts movement.

Question 49 Why is proline commonly found in collagen despite disrupting α-helices?

Its rigid ring structure contributes to collagen's unique triple-helical conformation rather than an α-helix.

Question 50 A mutation replaces cysteine with serine in a protein stabilized by disulfide bonds. Predict the most likely consequence.

Protein stability would decrease because serine cannot form disulfide bonds.

Question 51 What is the primary role of cysteine's sulfhydryl group in protein structure?

Formation of covalent disulfide bonds between cysteine residues.

Question 52 Why are disulfide bonds especially important in extracellular proteins?

They provide additional structural stability in the extracellular environment.

Question 53 Which amino acid can function as an important intracellular antioxidant precursor?

Cysteine, through its role in glutathione synthesis.

Question 54 Which amino acid serves as the precursor of serotonin, melatonin, and niacin?

Tryptophan.

Question 55 Which amino acid serves as the precursor of dopamine, norepinephrine, epinephrine, and thyroid hormones?

Tyrosine.

Question 56 Which amino acid serves as the precursor of histamine?

Histidine.

Question 57 Which amino acid serves as the precursor of nitric oxide?

Arginine.

Question 58 Which amino acid serves as the major methyl-group donor through S-adenosylmethionine (SAM)?

Methionine.

Question 59 A patient has impaired methylation reactions due to decreased SAM production. Deficiency of which amino acid is most directly responsible?

Methionine.

Question 60 A patient develops unstable extracellular proteins because covalent cross-links cannot form between amino acid side chains. Which amino acid is most likely affected?

Cysteine.

Question 61 What does it mean for an amino acid to be amphoteric?

It can act as either an acid or a base depending on the environment.

Question 62 Why can amino acids act as buffers?

Because they contain ionizable groups that can accept or donate protons.

Question 63 What is the pH of a solution?

The negative logarithm of the hydrogen ion concentration.

Question 64 What is the Henderson-Hasselbalch equation used for?

To relate pH, pKa, and the ratio of a weak acid to its conjugate base.

Question 65 What is a buffer?

A solution that resists changes in pH when acid or base is added.

Question 66 What is the best buffering condition for a weak acid and its conjugate base?

When the pH is equal to the pKa.

Question 67 How far from the pKa can a conjugate acid-base pair still function effectively as a buffer?

Within about one pH unit above or below the pKa.

Question 68 What happens to a weak acid when a strong acid is added to its buffer system?

The conjugate base accepts protons and is converted to the weak acid form.

Question 69 What happens to a weak acid when a strong base is added to its buffer system?

The weak acid donates protons and is converted to the conjugate base form.

Question 70 What is the isoelectric point of an amino acid?

The pH at which the amino acid has no net charge.

Question 71 At the isoelectric point, what form of the amino acid predominates?

The zwitterionic or dipolar form.

Question 72 For an amino acid with no ionizable side chain, how is the isoelectric point calculated?

By averaging the two pKa values of the α-carboxyl and α-amino groups.

Question 73 What is the pI of alanine according to the slide example?

5.7.

Question 74 At pH values below the pI, what is the net charge of the amino acid?

Positive.

Question 75 At pH values above the pI, what is the net charge of the amino acid?

Negative.

Question 76 What is the pKa of the α-carboxyl group of amino acids in general?

About 2.

Question 77 What is the pKa of the α-amino group of amino acids in general?

About 9.

Question 78 Which amino acid side chain can ionize within the physiologic pH range?

Histidine.

Question 79 Why is histidine important in buffering proteins such as hemoglobin?

Because its side chain can accept or donate protons near physiologic pH.

Question 80 A protein sample is run in an electric field at a pH above its pI. What will be the direction of movement?

It will move toward the positive electrode because it has a net negative charge.

Question 81 What is a peptide?

A compound formed when amino acids are linked together by peptide bonds.

Question 82 What is the chemical basis of a peptide bond?

It is formed by linkage between the carboxyl group of one amino acid and the amino group of another.

Question 83 In what direction are peptide sequences read?

From the N-terminus to the C-terminus.

Question 84 What is the N-terminus of a peptide?

The end with the free amino group.

Question 85 What is the C-terminus of a peptide?

The end with the free carboxyl group.

Question 86 Why is peptide directionality important?

Because peptide sequences are written and interpreted in a specific N-to-C orientation.

Question 87 What is glutathione?

A tripeptide composed of glutamate, cysteine, and glycine.

Question 88 Why is glutathione clinically and biochemically important?

It functions in antioxidant defense and detoxification.

Question 89 What is TRH?

Thyrotropin-releasing hormone, a peptide hormone.

Question 90 Name two peptide hormones mentioned in the slides.

Oxytocin and vasopressin.

Question 91 What is aspartame in chemical terms?

An artificial sweetener that is a peptide-derived compound.

Question 92 What is the primary structure of a protein?

Its linear amino acid sequence.

Question 93 What type of bond defines primary protein structure?

Peptide bonds.

Question 94 How does a mutation in amino acid sequence affect protein structure?

It changes the primary structure and can alter all higher levels of folding and function.

Question 95 What is secondary protein structure?

Local folding patterns such as α-helices, β-sheets, and turns.

Question 96 What stabilizes secondary structure?

Hydrogen bonds between backbone groups.

Question 97 What is the tertiary structure of a protein?

The full three-dimensional folding of one polypeptide chain.

Question 98 What is the quaternary structure of a protein?

The association of two or more polypeptide subunits.

Question 99 Give one example of a protein with quaternary structure.

Hemoglobin.