Amino Acids, Peptides, Protein Primary

Structure

Chapter 5

Amino Acids

• Basic structural units of proteins

• All have 3 common functional grps:– -NH2, -COOH, -H

• Individual aa’s each have different R grp

• These 4 grps att’d to C

• At neutral pH, exist as dipolar, or zwitterion, where amino grp exists as NH3+, carboxyl grp exists as COO-

• Chiral C, so have D, L stereoisomers– L form aa’s polymerize

to proteins

• Side chains vary in size, shape, charge, reactivity, H-bond capacity

• Five groups of aa’s, based on R grp similarities

• Some notes:– Glycine is only optically inactive aa– Cysteine has highly reactive sulfhydryl grp– Histidine R grp may be proton donor or

acceptor at physio pH

• 1) Nonpolar w/ aliphatic R grps– Glycine (Gly, G)– Alanine (Ala, A) – Valine (Val, V)– Leucine (Leu, L)– Isoleucine (Ile, I)– Proline (Pro, P)

• 2) Aromatic R grps– Phenylalanine (Phe, F)

– Tyrosine (Tyr, Y)

– Tryptophan (Trp, W)• So these are quite

hydrophobic

• 3) Polar w/ uncharged R grps– Serine (Ser, S)– Threonine (Thr, T)– Cysteine (Cys, C)– Methionine (Met, M)– Asparagine (Asn, N)– Glutamine (Gln, Q)

• 4) Polar w/ + charged R grps at physio pH– Lysine (Lys, K)

– Arginine (Arg, R)

– Histidine (His, H)

• 5) Polar w/ - charged R grps at physio pH– Aspartate (Asp, D)

– Glutamate (Glu, E)

Amino Acid Titration Curves

• Aa’s are weak acids, so can construct titration curves for each– REMEMBER: Add OH-, measuring change in

pH as titrate w/ OH-. Plot OH- added on x axis vs. pH on y axis

• These weak acids have 2 abstractable H’s, both on grps att’d to C: one on carboxyl grp, one on amino grp

• So have 2 inflection pts– Shape of each inflection is similar to inflection

seen with monoprotic acid (seen last chapter)– So each aa has 2 pKa’s

• At midpoint of titration ([OH-]=1 eq), cmpd is fully dipolar– Has no net electrical charge– Called isoelectric point– Isoelectric pH = pI– Each amino acid has characteristic pI– At any pH<pI, aa has net + charge– At any pH>pI, aa has net - charge

• pKa1 <<<< pKa2– First H+ released from aa is much more easily

given up than second H+

• 2 pKa’s = 2 regions of buffering capacity

• Aa’s w/ ionizable R grps (lys, arg, his) have 3rd pKa

• Two aa’s can be linked by peptide bonds to yield a dipeptide– Condensation rxn; H2O removed

– Endothermic rxn– Stable under physio cond’s; broken w/ boiling

in strong acid/base

• In dipeptide bond, carboxyl of aa1 joined to amino of aa2

• In living systems, peptide bond form’n assisted by ribosomes in translation process

• Oligopeptide = several aa’s joined by peptide bonds

• Polypeptide = many aa’s = small protein– Protein commonly MW . 10,000

• Aa residue of peptide w/ free amino grp called amino terminus

• Aa residue of peptide w/ free carboxyl grp = carboxy terminus

• At neutral pH, peptides have 1 free NH3+ and 1 free COO-– BUT R grps on each aa

may be ionized

– Each peptide has characteristic pI

– Peptide ionization = sum of that of all R grps of aa’s which make up the peptide