The Amino Acids

BIOCHEM 301 SPRING 2016

Lecture 3
Monday, January 25, 2016

alpha carbon

connects to carboxylic
acid of another amino acid

connects to amine
of another amino acid

R-group
sidechain

Amino Acid Stereochemistry

L-amino acid
(normal form)

D-amino acid

Protonation States

Free amino acid:

pKa: 1.8-2.6

pKa: 9.0-10.8

Protonation States

Free amino acid:

pKa: 1.8-2.6

As part of polypeptide:

pKa: 9.0-10.8

Protonation States

As part of polypeptide:

Protonation would result in

the loss of resonance.
Deprotonation would result
in negatively charged N.

Name

Three-Letter
Code

One-Letter Code

Alanine

Ala

Arginine

Arg

Aspartate

Asp

Asparagine

Asn

Cysteine

Cys

Glycine

Gly

Glutamate

Glu

Glutamine

Gln

Histidine

His

Isoleucine

Ile

Leucine

Leu

Lysine

Lys

Methionine

Met

Phenylalanine

Phe

Proline

Pro

Serine

Ser

Threonine

Thr

Tryptophan

Trp

Tyrosine

Tyr

Valine

Val

Glycine

Alanine

Valine

Leucine

Isoleucine

Methionine

Proline

Phenylalanine

Tyrosine

Tyrosine

pKa: ~10
protonated: H-bond donor/acceptor
deprotonated: H-bond acceptor, nucleophile

Tryptophan

Tryptophan

not acidic: removing a proton

would put a negative charge
and extra lone pair on N

not basic: accepting a proton

would require disrupting
aromaticity (lone pair is in p
orbital, part of aromatic system)

Tryptophan

H-bond donor

not an H-bond acceptor:

lone pair is in p orbital and
part of aromatic system

Serine

pKa: 14-16
H-bond donor? H-bond acceptor? nucleophile?

Cysteine

pKa: ~8

Cysteine and Disulfide Bonds

Threonine

pKa: 16-18

Aspartate

pKa: ~3.6

Asparagine

Glutamate

pKa: ~4.3

Glutamine

Lysine

pKa: ~10.5

Arginine

pKa: ~12.5

unfavorable

favorable

unfavorable

favorable

favorable

favorable

Histidine

Histidine

pKa: ~6
lone pair is sp2-hybridized
and can easily gain a proton

Histidine

deprotonating this N would

result in a negatively charge
N, which is unfavorable

Histidine

neutral His has two roughly equivalent tautomers

Histidine

protonated His has two roughly equivalent resonance structures

His vs. Trp

lone pair is sp2-hybridized

(not part of aromaticity)

lone pair is in p orbital

(part of aromaticity)

Thr vs. Ser vs. Tyr vs. Cys

pKa: 16-18

pKa: 14-16

pKa: ~10

pKa: ~8

His vs. Lys vs. Arg

pKa: ~6
pKa: ~10.5
pKa: ~12.5
sp2 bonds less readily sp3 bonds readilyresonance stabilization

Asp vs. Glu

pKa: ~3.6

pKa: ~4.5

Asp, Asn, Glu, Gln

pKa: ~3.6

no sidechain
protonation

pKa: ~4.5

no sidechain
protonation

Val, Leu, Ile

Ala and Phe

Hydrophobic

Hydrophobic?

Perturbation of pKa Values

What factors could raise a sidechain pKa from
its normal value?
What factors could lower a sidechain pKa from
its normal value?

FYI: Essential Amino Acids

Essential (humans do not make, must have in
diet): Arg*, His, Ile, Leu, Lys, Met, Phe, Thr, Trp,
Val
Non-essential (humans make, not needed in
diet): Ala, Asn, Asp, Cys, Glu, Gln, Gly, Pro, Ser,
Tyr*

Other Amino Acids

4-hydroxproline is found in collagen
Ornithine and citrulline are N metabolism
intermediates.

4-hydroxyproline

ornithine

citrulline