So now that we've covered trypsin, in this video we're going to focus on chymotrypsin. Chymotrypsin is different from trypsin in that it has a preference for which amino acid residues it recognizes for cleavage. Chymotrypsin prefers breaking aromatic amino acid residues which are Phenylalanine, Tyrosine, and Tryptophan, or, humorously referred to as 'fat young whippersnappers'. You can think of trypsin and chymotrypsin as brothers. Since they are brothers, they both cleave on the carboxyl side of the residues they recognize for cleavage.

Trypsin is the older, more responsible brother, and it's very particular, cleaving like a knight's sword. Trypsin's cleavage is specific, only after lysine and arginine. On the other hand, chymotrypsin is the younger brother who is much more chill and relaxed. Unlike trypsin's precise cleavage, chymotrypsin will slowly cleave other residues over time, beyond the aromatic amino acids, including leucine and methionine residues.

Below, we have a visualization to help you remember how chymotrypsin conducts its cleavage. Chymotrypsin can be humorously thought of as saying, "Come on, trypsin." This relaxed approach is aimed at suggesting trypsin not be so strict only to cleave after lysine and arginine but to also consider other residues over time. The mnemonic "Free your worries like me" helps us remember the amino acid residues chymotrypsin cleaves, where 'F' stands for phenylalanine, 'Y' for tyrosine, 'W' for tryptophan, and 'like me' for leucine and methionine.

The residues that are color-coded in red are those chymotrypsin starts to cleave beyond its primary preferences of aromatic amino acids. Through the mnemonic 'free your worries like me', you'll remember the residues chymotrypsin recognizes for cleavage. In the current example, a tetrapeptide with four amino acid residues, it’s clear only one amino acid residue is recognized for cleavage: Phenylalanine. Hence, it will cleave after phenylalanine, leaving another fragment with alanine and serine.

Moving forward in our practice problems, we will first assume chymotrypsin will cleave its preferred residues unless indicated otherwise. These preferred residues are aromatic amino acids: Phenylalanine, Tyrosine, and Tryptophan. The leucine and methionine will only be cleaved at a very slow rate if enough time is provided. Hopefully, this explanation helps you remember how chymotrypsin performs its cleavage, and you'll be ready to practice in our next video. I'll see you there.