3.1 Structure and properties of amino acids

Amino acids are the building blocks of proteins, each with a unique side chain that determines its properties. They have an amino group, a carboxyl group, and a central alpha carbon, existing as zwitterions at physiological pH.

Amino acids come in essential and nonessential types, with L-forms being the most common in proteins. Their isoelectric point (pI) determines their charge at different pH levels, affecting their behavior in various biological and experimental contexts.

Amino Acid Structure

Basic Components and Zwitterionic Form

• Amino acids are the building blocks of proteins consisting of an amino group ($-NH_2$), a carboxyl group ($-COOH$), and a variable side chain (R-group) attached to a central alpha carbon ($C_\alpha$)
• At physiological pH, amino acids exist predominantly as zwitterions where the amino group is protonated ($-NH_3^+$) and the carboxyl group is deprotonated ($-COO^-$)
• The zwitterionic form of amino acids is electrically neutral overall due to the positive charge on the amino group balancing the negative charge on the carboxyl group
• Examples of amino acids in their zwitterionic form include glycine (simplest amino acid with R-group as hydrogen) and alanine (R-group as methyl, $-CH_3$)

R-group Diversity and Chirality

• The R-group, also known as the side chain, is unique to each amino acid and determines its specific chemical properties (polarity, hydrophobicity, charge, etc.)
• Amino acids are chiral molecules (except glycine) due to the presence of four different groups attached to the central alpha carbon ($C_\alpha$)
• Chirality refers to the property of a molecule being non-superimposable on its mirror image, similar to left and right hands
• The two mirror-image forms of amino acids are called L- and D-amino acids, with L-amino acids being the predominant form found in proteins

Amino Acid Types

Essential and Nonessential Amino Acids

• Essential amino acids cannot be synthesized by the human body and must be obtained through diet (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine)
• Nonessential amino acids can be synthesized by the body and are not required to be consumed in the diet (alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine)
• Some amino acids are considered conditionally essential, meaning they become essential under certain conditions (arginine during growth, cysteine when methionine intake is low)

L- and D-Amino Acids

• L-amino acids are the predominant form found in proteins and are named after their configuration at the alpha carbon, with the amino group on the left when the carboxyl group is oriented downward
• D-amino acids are the mirror-image form of L-amino acids and are rare in proteins but can be found in some bacterial cell walls and certain antibiotics (gramicidin, valinomycin)
• The incorporation of a D-amino acid into a protein can significantly alter its structure and function due to the change in chirality
• Examples of L-amino acids include L-alanine and L-serine, while their mirror-image counterparts are D-alanine and D-serine

Amino Acid Properties

Isoelectric Point (pI)

• The isoelectric point (pI) is the pH at which an amino acid or protein has a net charge of zero due to the balance of positive and negative charges on its ionizable groups
• At a pH below the pI, the amino acid or protein will have a net positive charge due to protonation of the amino group and other basic side chains (lysine, arginine, histidine)
• At a pH above the pI, the amino acid or protein will have a net negative charge due to deprotonation of the carboxyl group and other acidic side chains (aspartic acid, glutamic acid)
• The pI of an amino acid or protein depends on the number and type of ionizable groups present in its structure (amino group, carboxyl group, and side chains)
• The pI can be used to predict the solubility and mobility of amino acids and proteins in different pH environments, which is important for techniques such as isoelectric focusing and ion-exchange chromatography