MCAT Biochemistry Review
Chapter 1: Amino Acids, Peptides, and Proteins
Nearly every part of a cell involves proteins in some way, from the nucleus to the mitochondria to the cell membrane. The MCAT will test your understanding of key concepts regarding amino acids because the amino acids that compose the protein determine its structure. In the next chapter, we'll discuss the best-known function of proteins: their role as enzymes.
Amino Acids Found in Proteins
· Amino acids have four groups attached to a central (α) carbon: an amino group, a carboxylic acid group, a hydrogen atom, and an R group.
o The R group determines chemistry and function of that amino acid.
o Twenty amino acids appear in the proteins of eukaryotic organisms.
· The stereochemistry of the α-carbon is L for all amino acids in eukaryotes.
o D-amino acids can exist in prokaryotes.
o All amino acids except cysteine have (S) configuration.
o All amino acids are chiral except glycine, which has a hydrogen atom as its R group.
· Side chains can be polar or nonpolar, aromatic or nonaromatic, charged or uncharged.
o Nonpolar, nonaromatic: glycine, alanine, valine, leucine, isoleucine, methionine, proline
o Aromatic: tryptophan, phenylalanine, tyrosine
o Polar: serine, threonine, asparagine, glutamine, cysteine
o Negatively charged (acidic): aspartate, glutamate
o Positively charged (basic): lysine, arginine, histidine
· Amino acids with long alkyl chains are hydrophobic, and those with charges are hydrophilic; many others fall somewhere in between.
Acid–Base Chemistry of Amino Acids
· Amino acids are amphoteric; that is, they can accept or donate protons.
· The pKa of a group is the pH at which half of the species is deprotonated; [HA] = [A–].
· Amino acids exist in different forms at different pH values.
o At low (acidic) pH, the amino acid is fully protonated.
o At pH near the pI of the amino acid, the amino acid is a neutral zwitterion.
o At high (alkaline) pH, the amino acid is fully deprotonated.
· The isoelectric point (pI) of an amino acid without a charged side chain can be calculated by averaging the two pKa values.
· Amino acids can be titrated.
o The titration curve is nearly flat at the pKa values of the amino acid.
o The titration curve is nearly vertical at the pI of the amino acid.
· Amino acids with charged side chains have an additional pKa value, and their pI is calculated by averaging the two pKa values that correspond to protonation and deprotonation of the zwitterion.
o Amino acids without charged side chains have a pI around 6.
o Acidic amino acids have a pI well below 6.
o Basic amino acids have a pI well above 6.
Peptide Bond Formation and Hydrolysis
· Dipeptides have two amino acid residues; tripeptides have three. Oligopeptides have a “few” amino acid resides (<20); polypeptides have “many” (>20).
· Forming a peptide bond is a condensation or dehydration reaction (releasing one molecule of water).
o The nucleophilic amino group of one amino acid attacks the electrophilic carbonyl group of another amino acid.
o Amide bonds are rigid because of resonance.
· Breaking a peptide bond is a hydrolysis reaction.
Primary and Secondary Protein Structure
· Primary structure is the linear sequence of amino acids in a peptide and is stabilized by peptide bonds.
· Secondary structure is the local structure of neighboring amino acids, and is stabilized by hydrogen bonding between amino groups and nonadjacent carboxyl groups.
o α-helices are clockwise coils around a central axis.
o β-pleated sheets are rippled strands that can be parallel or antiparallel.
o Proline can interrupt secondary structure because of its rigid cyclic structure.
Tertiary and Quaternary Protein Structure
· Tertiary structure is the three-dimensional shape of a single polypeptide chain, and is stabilized by hydrophobic interactions, acid–base interactions (salt bridges), hydrogen bonding, and disulfide bonds.
o Hydrophobic interactions push hydrophobic R groups to the interior of a protein, which increases entropy of the surrounding water molecules and creates a negative Gibbs free energy.
o Disulfide bonds occur when two cysteine molecules are oxidized and create a covalent bond to form cystine.
· Quaternary structure is the interaction between peptides in proteins that contain multiple subunits.
· Proteins with covalently attached molecules are termed conjugated proteins. The attached molecule is a prosthetic group, and may be a metal ion, vitamin, lipid, carbohydrate, or nucleic acid.
· Both heat and increasing solute concentration can lead to loss of three-dimensional protein structure, which is termed denaturation.
Answers to Concept Checks
1. The four groups are an amino group (–NH2), a carboxylic acid group (–COOH), a hydrogen atom, and an R group.
2. All eukaryotic amino acids are L. All eukaryotic amino acids are (S), with the exception of cysteine (because cysteine is the only amino acid with an R group that has a higher priority than a carboxylic acid according to Cahn–Ingold–Prelog rules).
3. Nonpolar, nonaromatic: glycine, alanine, valine, leucine, isoleucine, methionine, proline
§ Aromatic: tryptophan, phenylalanine, tyrosine
§ Polar: serine, threonine, asparagine, glutamine, cysteine
§ Negatively charged/acidic: aspartate, glutamate
§ Positively charged/basic: lysine, arginine, histidine
4. Hydrophobic amino acids tend to reside in the interior of a protein, away from water. Hydrophilic amino acids tend to remain on the surface of the protein, in contact with water.
1. pH = 1: +NH3CRHCOOH; pH = 7: +NH3CRHCOO–; pH = 11: NH2CRHCOO–
2. Aspartic acid: pI = (1.88 + 3.65) ÷ 2 = 2.77
§ Arginine: pI = (9.04 + 12.48) ÷ 2 = 10.76
§ Valine: pI = (2.32 + 9.62) ÷ 2 = 5.97
1. These species differ by the number of amino acids that make them up: amino acid = 1, dipeptide = 2, tripeptide = 3, oligopeptide = “few” (<20), polypeptilie = “many” (>20)
2. Water (H2O)
3. 4: Val – Phe; Glu – Lys – Tyr; Ile – Met – Tyr; Gly–Ala. A single amino acid on its own is not considered an oligopeptide.
Primary structure (1°)
Linear sequence of amino acids in chain
Peptide (amide) bond
Secondary structure (2°)
Local structure determined by nearby amino acids
· β-pleated sheet
2. Proline's rigid structure causes it to introduce kinks in α-helices, or create turns in β-pleated sheets.
Tertiary structure (3°)
Three-dimensional shape of protein
· Hydrophobic interactions
· Acid–base/salt bridges
· Disulfide links
· van der Waals forces
· Hydrogen bonds
· Ionic bonds
· Covalent bonds
Quaternary structure (4°)
Interaction between separate subunits of a multisubunit protein
Same as tertiary structure
2. Moving hydrophobic residues to the interior of a protein increases entropy by allowing water molecules on the surface of the protein to have more possible positions and configurations. This positive ΔS makes ΔG < 0, stabilizing the protein.
1. Heat denatures proteins by increasing their average kinetic energy, thus disrupting hydrophobic interactions. Solutes denature proteins by disrupting elements of secondary, tertiary, and quaternary structure.
Equations to Remember
(1.1) Isoelectric point of a neutral amino acid:
(1.2) Isoelectric point of an acidic amino acid:
(1.3) Isoelectric point of a basic amino acid:
· Biochemistry Chapter 2
· Biochemistry Chapter 3
o Nonenzymatic Protein Function and Protein Analysis
· Biochemistry Chapter 7
o RNA and the Genetic Code
· Biology Chapter 9
o The Digestive System
· General Chemistry Chapter 7
· Organic Chemistry Chapter 9
o Carboxylic Acid Derivatives