BCH 204 Essentials: Structure, Properties, and Functions of the 20 Amino Acids

Generic structure: Name the four groups attached to the alpha carbon in a standard amino acid.

1) Amino group (usually NH3+ at physiological pH) 2) Carboxyl group (usually COO- at physiological pH) 3) Hydrogen atom (H) 4) Side chain (R group)

Define "zwitterion" in the context of amino acids.

A zwitterion is a form of an amino acid that carries both a positive and a negative charge on different atoms but has an overall net charge of zero (e.g., NH3+ and COO- at pH ~7.4).

Which amino acid is the only non-chiral standard amino acid and why?

Glycine, because its side chain is just a hydrogen atom, so the alpha carbon is bonded to two identical groups (H), making it achiral.

List the positively charged (basic) amino acids at physiological pH.

Lysine (Lys, K), Arginine (Arg, R), Histidine (His, H – often partially protonated near pH 7.4).

List the negatively charged (acidic) amino acids at physiological pH.

Aspartate (Asp, D) and Glutamate (Glu, E).

Name the aromatic amino acids.

Phenylalanine (Phe, F), Tyrosine (Tyr, Y), and Tryptophan (Trp, W).

Glycine

Gly, G – Nonpolar (hydrophobic)

Alanine

Ala, A – Nonpolar (hydrophobic)

Valine

Val, V – Nonpolar (hydrophobic)

Leucine

Leu, L – Nonpolar (hydrophobic)

Isoleucine

Ile, I – Nonpolar (hydrophobic)

Methionine

Met, M – Nonpolar (hydrophobic)

Glycine (Gly, G)

Side chain: H. Smallest amino acid, achiral, very flexible. Common in tight turns and where backbone needs high flexibility.

Alanine (Ala, A)

Side chain: CH3. Simple, moderately hydrophobic methyl group. Often used as a neutral substitution in mutagenesis studies.

Valine (Val, V)

Side chain: CH(CH3)2 (isopropyl). Branched at the β-carbon. Hydrophobic and commonly found in protein cores and β-sheets.

Leucine (Leu, L)

Side chain: CH2-CH(CH3)2. Very common, strongly hydrophobic. Frequently buried in protein cores and α-helices.

Isoleucine (Ile, I)

Side chain: CH(CH3)-CH2-CH3. Hydrophobic, branched with two chiral centers. Often found in hydrophobic cores.

Methionine (Met, M)

Side chain: CH2-CH2-S-CH3 (thioether). Behaves largely nonpolar. Common in cores; encoded by the start codon AUG in translation.

Serine (Ser, S): side chain and class?

Side chain: -CH2-OH. Class: polar uncharged (alcohol). Can donate and accept hydrogen bonds; common on protein surfaces.

Threonine (Thr, T): key structural feature?

Side chain: -CH(OH)-CH3. Polar uncharged alcohol with a chiral beta carbon. Forms hydrogen bonds and is often involved in recognition and phosphorylation.

Asparagine (Asn, N) vs Glutamine (Gln, Q): main difference?

Both are polar uncharged amides. Asn: -CH2-CONH2 (shorter). Gln: -CH2-CH2-CONH2 (one extra CH2).

Cysteine (Cys, C): special property?

Side chain: -CH2-SH (thiol). Can form disulfide bonds (-S-S-) with another Cys under oxidizing conditions, stabilizing protein structure.

Aspartate (Asp, D): charge and side chain at pH 7?

Side chain: -CH2-COO−. Typically deprotonated and negatively charged at physiological pH; acidic amino acid.

Glutamate (Glu, E): mnemonic vs Asp?

Side chain: -CH2-CH2-COO− (longer than Asp). Mnemonic: "Glu is Greater" (one extra CH2) than Asp.

Rule: pH vs pKa and Protonation

If pH < pKa, the group is mostly protonated. If pH > pKa, the group is mostly deprotonated. At pH ≈ pKa, both forms are present in similar amounts.

Acidic Group Charge Pattern

Acidic groups (COOH, SH, phenolic OH): protonated form is neutral (0), deprotonated form carries −1 charge.

Basic Group Charge Pattern

Basic groups (NH3+, imidazole, guanidinium): protonated form carries +1 charge, deprotonated form is neutral (0).

Typical pKa: α-Carboxyl

α-carboxyl group pKa is around 2. At physiological pH (~7.4) it is mostly deprotonated, carrying −1 charge.

Typical pKa: α-Amino

α-amino group pKa is around 9. At physiological pH (~7.4) it is mostly protonated, carrying +1 charge.

Side Chain pKa: Asp and Glu

Asp and Glu side chain carboxyl pKa values are about 3.9–4.2. At pH 7 they are deprotonated and carry −1 each.

Isoelectric point (pI)

The pH at which a molecule has zero net charge; positive and negative charges balance, though individual groups may still be charged.

pI formula for amino acids with only two ionizable groups

For amino acids without ionizable side chains: pI = (pKa of α-COOH + pKa of α-NH3+) / 2.

Acidic side-chain amino acids: which pKa’s to average for pI?

For Asp and Glu, the neutral form lies between the two lowest pKa values, so pI ≈ average of pKaα-COOH and pKa of the side-chain COOH.

Basic side-chain amino acids: which pKa’s to average for pI?

For Lys and Arg (and often His), the neutral form lies between the two highest pKa values, so pI ≈ average of pKaα-NH3+ and pKa of the basic side chain.

Charge rule for acidic groups (COOH, phenol, thiol)

pH << pKa → protonated, charge 0; pH >> pKa → deprotonated, charge −1.

Charge rule for basic groups (NH3+, imidazolium, guanidinium)

pH << pKa → protonated, charge +1; pH >> pKa → deprotonated, charge 0.

Define an essential amino acid.

An amino acid that **cannot be synthesized in sufficient amounts by the human body** and therefore **must be obtained from the diet** under normal physiological conditions.

List the 9 essential amino acids for healthy adult humans.

**Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine.**

Define a conditionally essential amino acid.

An amino acid that is usually synthesized endogenously, but whose **biosynthesis becomes insufficient** in certain conditions (e.g., prematurity, trauma, sepsis, metabolic disease), making **dietary intake necessary**.

Give two examples of conditionally essential amino acids and when they become essential.

**Arginine** – essential in infants and during severe stress or trauma. **Tyrosine** – essential in phenylketonuria (PKU) because conversion from phenylalanine is impaired. (Also: cysteine when methionine is low; glutamine in critical illness.)

What is the main difference between PDCAAS and DIAAS?

**PDCAAS** uses fecal digestibility of total protein and truncates scores at 1.0. **DIAAS** uses ileal digestibility of individual essential amino acids and does **not** truncate scores, giving a more accurate measure of protein quality.

Why are branched-chain amino acids (Leu, Ile, Val) essential?

Humans **lack the enzymes** required to synthesize their branched carbon skeletons from central metabolic intermediates, so these amino acids must come from the diet.

Primary structure

The linear sequence of amino acids in a polypeptide chain, from N-terminus to C-terminus.

Secondary structure

Local, regularly repeating backbone conformations such as α-helices, β-sheets, and β-turns, stabilized mainly by backbone hydrogen bonds.

α-helix

A right-handed helical secondary structure where each C=O of residue i hydrogen bonds to N–H of residue i+4; side chains project outward.

β-sheet

A secondary structure formed by β-strands aligned side-by-side, with backbone hydrogen bonds between strands; side chains alternate above and below the sheet.

β-turn

A tight turn (often 4 residues long) that reverses the direction of the polypeptide chain, commonly enriched in Pro and Gly.

Ramachandran plot

A plot of allowed φ and ψ backbone angles for amino acid residues, showing preferred regions corresponding to helices and sheets.

Histidine (His)

Imidazole side chain with pKa near physiological pH; excellent general acid/base; key in catalytic triads and proton shuttling.

Serine (Ser)

Alcohol side chain; can be activated to a strong nucleophile in serine proteases; common phosphorylation site in signaling.

Cysteine (Cys)

Thiol side chain; forms thiolate nucleophiles, disulfide bonds, and redox switches; central in cysteine proteases and structural disulfides.

Methionine (Met)

Thioether side chain; initiating amino acid in translation; precursor of S-adenosylmethionine (SAM); can be reversibly oxidized to sulfoxide.

Glutamate (Glu)

Carboxylate side chain; major collector and donor of amino groups via transamination; substrate for glutamate dehydrogenase; precursor of glutamine and GABA.

Aspartate (Asp)

Carboxylate side chain; nitrogen donor in urea cycle and nucleotide synthesis; part of catalytic triads; involved in malate–aspartate shuttle.

List the 5 main property groups used to chunk the 20 amino acids.

1) Nonpolar, aliphatic (hydrophobic) 2) Aromatic 3) Polar, uncharged 4) Positively charged (basic) 5) Negatively charged (acidic)

Mnemonic for nonpolar, aliphatic amino acids (G, A, V, L, I, M, P).

"Grandma Always Visits London In May, Period."

Which amino acids are aromatic, and what is their mnemonic?

Phe (F), Tyr (Y), Trp (W). Mnemonic: "Fragrant Yellow Wine."

Name the positively charged amino acids and their 1-letter codes.

Lysine (K), Arginine (R), Histidine (H). Mnemonic: "Knights Ride Horses."

Which amino acids are negatively charged at physiological pH?

Aspartate (Asp, D) and Glutamate (Glu, E). Mnemonic: "Deadly Enemies."

Pair these: Aspartate vs Glutamate. Which is longer?

Glutamate (E) has one extra CH2 compared to Aspartate (D). Think: E for "Extra" methylene.

Side chain: CH2-COO- at pH 7. Name, 3-letter, 1-letter, classification?

Aspartate (Asp, D). Acidic, negatively charged at pH 7, polar.

Side chain: CH2-CH2-COO- at pH 7. Name, 3-letter, 1-letter?

Glutamate (Glu, E). Acidic, negatively charged at pH 7, polar.

Side chain: CH2-CONH2. Name, 3-letter, 1-letter?

Asparagine (Asn, N). Polar, uncharged.

Side chain: CH2-CH2-CONH2. Name, 3-letter, 1-letter?

Glutamine (Gln, Q). Polar, uncharged.

Side chain: CH2-OH. Name, 3-letter, 1-letter?

Serine (Ser, S). Polar, uncharged; can be phosphorylated.

Side chain: CH(OH)-CH3. Name, 3-letter, 1-letter?

Threonine (Thr, T). Polar, uncharged; can be phosphorylated.

Rule: pH vs pKa and protonation

If pH < pKa, the group is mostly protonated. If pH > pKa, the group is mostly deprotonated. Around pH = pKa, it is about 50/50.

Charge of acidic group when protonated vs deprotonated

Acidic group (e.g., COOH): protonated form is neutral (0); deprotonated form (COO−) carries −1 charge.

Charge of basic group when protonated vs deprotonated

Basic group (e.g., NH3+, Lys, Arg, His): protonated form is +1; deprotonated form is neutral (0).

pI formula: amino acid without ionizable side chain

pI ≈ (pKa of α-COOH + pKa of α-NH3+) / 2.

pI formula: acidic amino acid (Asp, Glu)

pI ≈ average of the two acidic pKa values: pKa of α-COOH and pKa of side-chain COOH.

pI formula: basic amino acid (Lys, Arg, His)

pI ≈ average of the two basic pKa values: pKa of α-NH3+ and pKa of the basic side chain.