An essential part of understanding biochemistry lies in the knowledge of amino acid structure as well as protein structure. Amino acids are the building blocks of proteins and thus influence the functions of all proteins including enzymes, hormones, antibodies, and storage proteins.

Image: Special features of selected amino acids with 1-letter abbreviation in parentheses. Source: MCAT-prep.com

Amino acids follow the structural blueprint of a carbon atom bonded to four different groups: an amino group, a carboxylic acid group, a hydrogen atom, and a side chain generally referred to as an R group or residue. Since it is bonded to four different groups, the carbon atom is called a chiral carbon. And like all chiral molecules, this chiral carbon gives amino acids optical activity, or the ability to rotate plane-polarized light.

Now because the carbon atom is bonded to a carbonyl carbon within the carboxylic acid, it is also considered an alpha carbon. So, when the term alpha amino acids is used it is referencing the alpha carbons they contain. Overall, it is the R groups that make each amino acid unique depending on how they differ in size, polarity, structure, shape, charge, hydrophobic or hydrophilic nature, and ability to hydrogen bond.

There are some specific amino acids to keep in mind for their special R groups and effect on protein structure…

Proline has a special R group, namely a rigid, cyclic alkyl containing a secondary alpha amino group. The R group of the smallest amino acid, glycine, is a flexible hydrogen atom making its alpha carbon no longer chiral (bonded to two hydrogens), yet allowing free rotation around that alpha carbon. Proline’s rigidity and glycine’s flexibility produce kinks in proteins’ secondary structure granting these special amino acids the name, “alpha helix breakers.”

The imidazole side chain of histidine has an approximate pKa of 6.5 which is close to physiological pH. This allows histidine to exist in its protonated and deprotonated forms simultaneously and position itself at the active site of enzymes for stabilizing or destabilizing substrates. Cysteine is another special amino acid in that its thiol R group forms disulfide bridges with other thiol groups thereby contributing to tertiary protein structure.

Disulfide bridges are in fact covalent bonds making them the strongest of all tertiary structure interactions. The oxidizing extracellular space favors disulfide bridge formation whereas the reducing intracellular space favors unbound thiol groups. When reduced, it is written as “cysteine” and when oxidized, it is written as “cystine” (without the e).

It is wise to memorize all 20 essential amino acids, including their respective R groups, as the MCAT will pose several questions pertaining to the charge of an amino acid or protein in a particular environment or the potential for hydrogen bonds or disulfide bridges to form. So, mastering this level of biochemistry will take you far on test day!