Amino Acids, Peptides, and Protein Structure (5D) - MCAT Chemical and Physical Foundations of Biological Systems

Gly, Ala, Val, Leu, Ile, Met, Pro. These amino acids have hydrocarbon side chains that lack polarity, making them hydrophobic and aliphatic in classification.

Phe, Tyr, Trp. Aromatic side chains contain benzene-like rings, distinguishing them from aliphatic or other polar groups.

Ser, Thr, Asn, Gln, Cys, Tyr. These side chains have polar groups like hydroxyls, amides, or thiols that do not ionize at physiological pH.

Lys, Arg, His. Basic side chains have high pKa values, remaining protonated and positively charged near neutral pH.

Asp, Glu. Acidic side chains have low pKa values, deprotonating to form negatively charged carboxylates near pH 7.

Glycine. Glycine lacks a side chain on its alpha carbon, preventing chirality unlike other amino acids with four different substituents.

Proline. Proline's side chain forms a ring with the alpha-amino group, restricting conformational flexibility in proteins.

Cysteine. The thiol group in cysteine can oxidize to form covalent disulfide bridges, stabilizing protein structure.

Tyrosine. Tyrosine's phenolic hydroxyl is a target for kinases in signal transduction due to its aromatic nature.

Serine and threonine. Aliphatic hydroxyl groups on serine and threonine are accessible for phosphorylation in regulatory processes.

Asparagine. Asparagine is formed by amidation of aspartate's carboxyl group, adding a polar, uncharged amide.

Glutamine. Glutamine results from amidation of glutamate's side chain carboxyl, providing a longer polar amide group.

Aspartate and glutamate. Carboxylate groups in aspartate and glutamate ionize at physiological pH, contributing acidity.

Molecule with both $+ $ and $-$ charges, net $0$. Amino acids form zwitterions at physiological pH where the carboxylic acid deprotonates and the amino group protonates, balancing charges.

$N$-terminus to $C$-terminus. Peptides are conventionally written and biosynthesized from the amino terminus to the carboxyl terminus, reflecting ribosomal synthesis direction.

Peptide (amide) bond. The peptide bond is an amide linkage formed between the carboxyl group of one amino acid and the amino group of another.

$H_2O$ (condensation/dehydration). Peptide bond formation is a dehydration reaction where water is eliminated from the carboxyl and amino groups.

Net charge $0$. The isoelectric point (pI) is the pH where the peptide's average net charge is zero due to balanced ionization states.

Henderson–Hasselbalch: $pH=pK_a+\log\frac{[A^-]}{[HA]}$. The Henderson-Hasselbalch equation describes the ionization equilibrium of weak acids, applied to amino acid functional groups.

Backbone hydrogen bonding. Hydrogen bonds between backbone carbonyls and amides stabilize regular secondary structures like alpha helices and beta sheets.

Linear amino acid sequence (covalent connectivity). Primary structure refers to the covalent sequence of amino acids in a protein, determining higher-level folding.

Overall $3$D fold of one polypeptide chain. Tertiary structure involves the spatial arrangement of a single chain, stabilized by side chain interactions.

Association of multiple polypeptide subunits. Quaternary structure arises from non-covalent interactions between separate polypeptide chains in multimeric proteins.

Hydrophobic effect. The hydrophobic effect drives nonpolar residues into the protein core to minimize water contact and maximize entropy.