Amino Acids and Peptides Lecture Notes

There are 20 amino acids used for protein synthesis.
Familiarity with their names and structural types (aromatic, basic, acidic, nonpolar) is useful.
Amino acids are the basic building blocks of peptides and proteins.
- Peptides are shorter polymers of amino acids.
- Proteins are longer polymers of amino acids.

Each amino acid monomer has:
- A carboxylic acid (carboxy) group.
- An amino group on the alpha carbon.
- A side chain (R group), which varies among amino acids and determines their unique properties.
All amino acids are chiral around the alpha carbon (except glycine).
- Asymmetric molecules have L and D isomers (mirror images).
- Only L isomers are found in proteins.
Amino acids possess both weakly acidic and weakly basic groups.
- The acid group (carboxyl group) deprotonates at a pH above 2.
- The amino group protonates at a pH below 9.
At intermediate pH levels (including neutral pH of 7), both groups are ionized.
- This results in a zwitterion, a molecule with both positive and negative charges.

Peptide bonds are formed by a covalent linkage between the carboxyl group of one amino acid and the amino group of another.
This is a type of amide bond, specifically referring to the carboxyl-amino linkage between amino acids.
The formation of a peptide bond is accompanied by the loss of a water molecule ( $H_2O$ ).
Polypeptides and proteins are characterized by:
- The number of amino acids covalently linked in the chain.
- The specific sequence of these amino acids.

A polypeptide is a zwitterion with:
- A positively charged N-terminal amino group.
- A negatively charged C-terminal carboxy group.
Most proteins have polypeptide chains with 50 to 2000 amino acid residues.
Shorter chains are called peptides or oligopeptides.
Some peptides can act as hormones.
The side chains of amino acids impart unique properties to the polypeptide or protein.

Leu-enkephalin is a pentapeptide (5 amino acids) with the sequence Tyrosine-Glycine-Glycine-Phenylalanine-Leucine.
It is an opioid peptide that modulates the perception of pain.
Tyrosine and phenylalanine have aromatic side chains.
Glycine has a hydrogen as its side chain.
Leucine has a branched side chain.
The directionality of the amino acid sequence is crucial for its function.
- Reversing the sequence would eliminate the opioid effect.

Proteins are synthesized from a repertoire of 20 α amino acids.
Approximately half of the amino acids have nonpolar side chains.
The other half have:
- Polar but uncharged side chains.
- Positively or negatively charged functional groups on their side chains.
Three-letter codes and one-letter abbreviations are used to represent each amino acid.
- Example: Tryptophan is TRP (three-letter code) and W (one-letter abbreviation).
- One-letter codes are not always intuitive and may require reference.

Simplest:
- Glycine (side chain: H)
- Alanine (side chain: methyl group)
Others (with longer hydrocarbon groups):
- Valine
- Leucine
- Isoleucine
- Branched-chain amino acids
Proline:
- Technically an imino acid.
- Its side chain forms a ring structure with the nitrogen on the alpha carbon.
Sulfur-containing:
- Methionine
- Cysteine
- Cysteine's sulfur is present as a sulfhydryl group, which can react with other sulfhydryl groups.
- Methionine has a longer hydrocarbon chain, and its sulfur atom is methylated.

Phenylalanine, tyrosine, and tryptophan have aromatic rings on their side chains.
Aromatic rings have alternating single and double bonds.
Phenylalanine and tryptophan are nonpolar and hydrophobic.
Tyrosine is similar to phenylalanine but has a hydroxyl group, making it more polar.
Tryptophan has a complex structure with fused rings.

Have an additional charged group on their side chains.
Acidic (negatively charged):
- Aspartate (Asp)
- Glutamate (Glu)
- Have an additional carboxyl group with a negative charge at the end of the side chain.
Basic (positively charged):
- Lysine (Lys)
- Arginine (Arg)
- Both have additional nitrogen groups and a net positive charge.
- Lysine has a second amino group.
- Arginine contains three nitrogens covalently bonded to the same carbon.
Histidine (His):
- Has a ring structure with two nitrogen and three carbon atoms (not aromatic).
- At a pH slightly below 7, it can accept an additional hydrogen ion and acquire a positive charge.
- Its pKa is near 6, so charged and non-charged forms are both present at neutral pH.
- Often found in the active site of enzymes, where its ability to bind and release protons contributes to catalysis.

Serine (Ser) and Threonine (Thr): contain hydroxyl groups.
- Tyrosine can also be included here due to its hydroxyl group on the aromatic ring.
Asparagine (Asn) and Glutamine (Gln):
- Derived from aspartate and glutamate.
- Have an amino group in amide linkage on the side chain carboxyl group.
- Result in highly polar, hydrophilic side chains that cannot ionize at physiological pH.

Side chains are very important and provide the unique properties of the molecule and its specificity for interacting with other molecules.
In larger proteins and polypeptides, the side chains determine the overall structure of the molecule.
In enzymes, the amino acid side chains are important in determining the substrate specificity, and they are the key components of the catalytic mechanism.

Cysteine's sulfhydryl group plays a major role in stabilizing protein structure, particularly in extracellular and secreted proteins.
Oxidation of two sulfhydryl groups results in the formation of a disulfide bridge, linking two cysteine side chains together.
This is an oxidation reaction involving the removal of two hydrogen atoms (or two electrons and two protons).

A small peptide hormone that stimulates the kidney to reabsorb water.
Contains nine amino acids with a disulfide bridge between two cysteine residues.
Has a net charge of zero with one positively charged arginine and one negatively charged glutamate.
Synthetic peptide analogs can be used as drugs for people who do not synthesize sufficient hormone.

A hormone secreted by the beta cells of the pancreas that regulates blood sugar levels.
Has two peptide chains (21 and 30 amino acids long) with different amino acid sequences.
The two chains are attached to each other by two disulfide bridges.
There is also a disulfide bridge that forms a loop within the A chain.