Question

Following is the primary structure of glucagon, a polypeptide hormone of 29 amino acids. Glucagon is produced in the \(\alpha\)-cells of the pancreas and helps maintain blood glucose levels in a normal concentration range. Which peptide bonds are hydrolyzed when this polypeptide is treated with each reagent? (a) Phenyl isothiocyanate (b) Chymotrypsin (c) Trypsin (d) \(\mathrm{BrCN}\)

Short answer

Question: Identify the peptide bonds that are hydrolyzed when glucagon is treated with (a) Phenyl isothiocyanate, (b) Chymotrypsin, (c) Trypsin, and (d) BrCN. Answer: (a) Phenyl isothiocyanate: The peptide bond at the N-terminus of glucagon would be hydrolyzed. (b) Chymotrypsin: Peptide bonds after aromatic and large hydrophobic amino acids (phenylalanine, tyrosine, or tryptophan) would be hydrolyzed. (c) Trypsin: Peptide bonds after positively charged amino acids (lysine and arginine) would be hydrolyzed. (d) BrCN: Peptide bonds after methionine residues would be hydrolyzed.

Step-by-step solution

(a) Phenyl isothiocyanate

Phenyl isothiocyanate (PITC) reacts with peptide bonds by breaking them at the N-terminus of a polypeptide chain. Therefore, only the peptide bond near the N-terminal amino acid would be hydrolyzed. In the case of glucagon, the amino acid at the N-terminus would be involved in hydrolysis.

(b) Chymotrypsin

Chymotrypsin is a serine protease that cleaves peptide bonds towards the carboxyl-terminal of aromatic and large hydrophobic amino acids, such as phenylalanine, tyrosine, and tryptophan. To identify where chymotrypsin would cleave glucagon, we need to find these amino acids in the given primary structure. Then, the peptide bonds after these amino acids would be hydrolyzed.

(c) Trypsin

Trypsin is another serine protease that cleaves peptide bonds towards the carboxyl-terminal of positively charged amino acids, such as lysine and arginine. To identify where trypsin would cleave glucagon, we need to locate these amino acids in the given primary structure. Then, the peptide bonds after these amino acids would be hydrolyzed.

(d) BrCN

Bromo cyanide (BrCN) selectively breaks peptide bonds at the carboxyl-terminal of methionine residues. To identify where BrCN would cleave glucagon, we need to locate methionine amino acids in the given primary structure. Then, the peptide bonds after these amino acids would be hydrolyzed.