Chymotrypsin and Trypsin Conversion: Discovering the Essential Amino Acid Supplements
Two important digestive enzymes, Chymotrypsin (or Trypsin), are well-studied for their ability to reduce proteins to smaller peptides. Chymotrypsin cleaves peptide chains on the carboxyl-side of lysine/arginine residues. Chymotrypsin cleaves those bonds with peptides on the carboxyl-side of trypsin and phenylalanine residues. These enzymes are different in sequence, so it is necessary to make certain amino acid substitutes for Trypsin and Chymotrypsin. To identify the necessary amino acid substitutions for conversion, it is important to know the sequences of the enzymes. The amino acid sequence of Trypsin has been determined to be Ala-Val-Asp-Arg-Ile-Gln-Gly-Ser-Thr-Asn-Lys-Lys-Glu-Glu-Asp-Glu-Gly-Gly-Ser-Gly-His (1). The amino acid sequence of Chymotrypsin has been determined to be Ala-Val-Asp-Ile-Tyr-Gln-Gly-Ser-Thr-Phe-Lys-Lys-Glu-Gly-Asp-Glu-Gly-Gly-Ser-Gly-His (2). Trypsin as well as chymotrypsin both play an important role in protein digestion. Both enzymes have their own specificities. While trypsin can cleave basic amino acids, such as lysine, arginine, and chymotrypsin preferentially, it can cleave hydrophobic amino compounds such as phenylalanine (tyrosine) and tryptophan.
Specific amino acid substitutions are required in order to convert trypsin to chymotrypsin. In a 2016 study (Kim and colleagues, 2016), it was found that certain amino acids can be substituted in trypsin’s active site to shift substrate specificity toward chymotrypsin. Asparagine can be substituted for serine in position 189, and histidine is replaced by arginine in place 193. This has been demonstrated to improve the enzyme’s preference towards hydrophobic amino compounds (Kim, et al. 2016,).