Amino acids have important roles in living organisms Subunits (building blocks) of peptides and proteins glutamate γ-aminobutyric acid (GABA) Neurotransmitters Metabolic intermediates

Proteins are synthesized from 20 ‘standard’ α-amino acids Proteins are synthesized from 20 ‘standard’ α-amino acids. Their names have 3- and 1-letter abbreviations. Alanine Ala A Methionine Met M Cysteine Cys C Asparagine Asn N Aspartate Asp D Proline Pro P Glutamate Glu E Glutamine Gln Q Phenylalanine Phe F Arginine Arg R Glycine Gly G Serine Ser S Histidine His H Threonine Thr T Isoleucine Ile I Valine Val V Lysine Lys K Tryptophan Trp W Leucine Leu L Tyrosine Tyr Y

Amino acid pKa’s vary because of attached functional groups (microenvironment influences acidity) FIGURE 3-11 Effect of the chemical environment on pKa. The pKa values for the ionizable groups in glycine are lower than those for simple, methyl-substituted amino and carboxyl groups. These downward perturbations of pKa are due to intramolecular interactions. Similar effects can be caused by chemical groups that happen to be positioned nearby—for example, in the active site of an enzyme.

Most amino acids are chiral, and are designated ‘d’ or ‘l’ based on Emil Fischer’s nomenclature FIGURE 3-4 Steric relationship of the stereoisomers of alanine to the absolute configuration of L- and D-glyceraldehyde. In these perspective formulas, the carbons are lined up vertically, with the chiral atom in the center. The carbons in these molecules are numbered beginning with the terminal aldehyde or carboxyl carbon (red), 1 to 3 from top to bottom as shown. When presented in this way, the R group of the amino acid (in this case the methyl group of alanine) is always below the α carbon. L-Amino acids are those with the α-amino group on the left, and D-amino acids have the α-amino group on the right.

The ‘Fischer projection’ is a simplified way to depict stereochemistry Fisher projection Vertical bonds point away from viewer (dashed wedges) Horizontal bonds point toward viewer (filled wedges) FIGURE 3-3 Stereoisomerism in α-amino acids. (a) The two stereoisomers of alanine, L- and D-alanine, are nonsuperposable mirror images of each other (enantiomers). (b, c) Two different conventions for showing the configurations in space of stereoisomers. In perspective formulas (b) the solid wedge-shaped bonds project out of the plane of the paper, the dashed bonds behind it. In projection formulas (c) the horizontal bonds are assumed to project out of the plane of the paper, the vertical bonds behind. However, projection formulas are often used casually and are not always intended to portray a specific stereochemical configuration. Chiral carbons may be left out entirely

How to identify the stereochemistry of an amino acid (d or l?) Fisher projection l-amino acid: d-amino acid: If projection is aligned with: carbon chain vertical carboxylate on top amino group on left = L amino group on right = D The CORN rule l-amino acid: d-amino acid: Orient the structure to look down the Ca-H bond Follow the other Ca substituents to spell CORN (carboxylate, R-group, amino): counterclockwise is l, clockwise is d

Nonstandard amino acids are found in modified proteins and as free metabolites FIGURE 3-8a Uncommon amino acids. (a) Some uncommon amino acids found in proteins. All are derived from common amino acids. Extra functional groups added by modification reactions are shown in red. Desmosine is formed from four Lys residues (the four carbon backbones are shaded in yellow). Note the use of either numbers or Greek letters to identify the carbon atoms in these structures.