🥼Organic Chemistry Unit 26 Review

Amino acids are the monomers that make up proteins. Each one shares the same core framework but differs in its side chain, and that side chain is what gives each amino acid its unique chemical personality. Understanding this structure is the foundation for everything else in protein chemistry.

Structural Features of Amino Acids

Every amino acid has the same general structure: a central $\alpha$ -carbon bonded to four groups:

An amino group ( $-NH_2$ )
A carboxyl group ( $-COOH$ )
A hydrogen atom
A side chain (R group) that varies from one amino acid to the next

The R group is what makes each amino acid different. Glycine has just a hydrogen as its R group (the simplest case), while alanine has a methyl group ( $-CH_3$ ).

Side chain classification sorts the 20 standard amino acids into five categories based on R group properties:

Nonpolar aliphatic (e.g., Glycine, Alanine, Valine): hydrocarbon-like side chains that avoid water
Aromatic (e.g., Phenylalanine, Tyrosine, Tryptophan): contain aromatic rings; can be polar or nonpolar depending on ring substituents
Polar uncharged (e.g., Serine, Threonine, Asparagine): side chains with groups like $-OH$ or $-CONH_2$ that can hydrogen-bond with water
Positively charged at pH 7.4 (Lysine, Arginine, Histidine): side chains carry a protonated nitrogen
Negatively charged at pH 7.4 (Aspartate, Glutamate): side chains carry a deprotonated carboxyl group

Chirality. Because the $\alpha$ -carbon has four different substituents, every amino acid except glycine is chiral. Glycine is the exception because its R group is just hydrogen, making two of the four groups identical. Naturally occurring amino acids are the L-stereoisomers. If you're asked to draw one, use a Fischer projection with the amino group on the left.

Because amino acids contain both an acidic group ( $-COOH$ ) and a basic group ( $-NH_2$ ), they are amphoteric: they can donate or accept protons depending on the pH of the solution.

Structural features of amino acids, Amino Acids and DNA and RNA Bases | Computational Chemistry Resources

Amino Acids as Zwitterions

At physiological pH (around 7.4), amino acids don't exist in their neutral "textbook" form. Instead, the carboxyl group loses its proton to become $-COO^-$ , and the amino group picks up a proton to become $-NH_3^+$ . The result is a zwitterion: a molecule that carries both a positive and a negative charge, with a net charge of zero.

This matters for a few reasons:

Zwitterions have high melting points and are water-soluble, which is why amino acids behave more like salts than typical small organic molecules.
Amino acids are amphiprotic in solution. In acidic conditions, the $-COO^-$ group gets protonated (amino acid acts as a base). In basic conditions, the $-NH_3^+$ group loses its proton (amino acid acts as an acid).

The isoelectric point (pI) is the specific pH at which a given amino acid has a net charge of exactly zero. For amino acids with nonpolar or uncharged polar side chains, pI is simply the average of the two $pK_a$ values (the one for the carboxyl group and the one for the amino group). For amino acids with ionizable side chains (like Lysine or Glutamate), you average the two $pK_a$ values closest to the zwitterionic form.

To calculate pI: identify the form with net zero charge, then average the two $pK_a$ values on either side of that form. $pI = \frac{pK_{a1} + pK_{a2}}{2}$

Structural features of amino acids, Amino Acids | Introduction to Chemistry

Essential vs. Nonessential Amino Acids

Essential amino acids are the nine that your body cannot synthesize on its own. You must get them from food. A helpful mnemonic: PVT TIM HaLL (Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Leucine, Lysine). Deficiency in any of these can impair growth, immune function, and tissue repair.

Nonessential amino acids (the remaining eleven, including Alanine, Serine, Glycine, Glutamic acid, and others) can be made by the body from metabolic intermediates. "Nonessential" doesn't mean unimportant; it just means your cells can produce them when needed.

Beyond building proteins, amino acids serve as precursors for other critical molecules:

Tryptophan is a precursor to the neurotransmitter serotonin.
Tyrosine is converted into dopamine and other catecholamines.
Glutamic acid is the most abundant excitatory neurotransmitter in the brain.
Several amino acids participate in the urea cycle and the glucose-alanine cycle, linking protein metabolism to energy metabolism and nitrogen balance.

Amino Acid Interactions and Properties

Once amino acids are incorporated into proteins, their side chains drive the protein's three-dimensional shape and stability.

Peptide bonds form through a condensation reaction between the carboxyl group of one amino acid and the amino group of the next, releasing water. The resulting chain of amino acids is called a polypeptide.

Key non-covalent and covalent interactions between side chains:

Disulfide bonds: Two cysteine residues can be oxidized to form a covalent $-S-S-$ bridge. These bonds lock parts of the protein structure in place and are especially important in secreted proteins like insulin.
Hydrogen bonding: Polar side chains (Serine, Threonine, Asparagine) form hydrogen bonds with each other or with the peptide backbone, stabilizing secondary and tertiary structure.
Hydrophobic interactions: Nonpolar side chains (Valine, Leucine, Isoleucine) cluster together in the protein interior to avoid water. This hydrophobic collapse is one of the main driving forces of protein folding.

The interplay of these interactions determines whether a protein folds correctly and functions properly.

🥼Organic Chemistry Unit 26 Review