Chymotrypsinogen

Chymotrypsinogen is the zymogen form of the serine protease chymotrypsin. It is synthesized by pancreatic acinar cells and secreted into the small intestine as an inactive proenzyme.

Activation occurs in the intestinal lumen. In the duodenum, enteropeptidase activates trypsinogen to trypsin; trypsin then cleaves chymotrypsinogen to form active chymotrypsin. A transient intermediate, pi-chymotrypsin, is rapidly converted to the mature enzyme, which consists of two polypeptide chains linked by disulfide bonds.

Chymotrypsin is a digestive serine protease that hydrolyzes peptide bonds on the carboxyl side of bulky hydrophobic residues, especially phenylalanine, tyrosine, and tryptophan. The enzyme belongs to the trypsin-like serine protease family and employs a catalytic triad of histidine, aspartate, and serine.

Structure: After activation, the enzyme is a two-chain protein with the heavy and light chains held together by disulfide bonds; the active site contains the catalytic triad and is active under physiological pH.

Genetics and variants: In humans, several chymotrypsinogen genes encode different isoforms; these zymogens share the same fundamental mechanism of activation by proteolysis to generate active chymotrypsin.

Clinical relevance: Measurements of chymotrypsin activity or chymotrypsinogen levels in clinical samples, such as feces, can be used as markers of pancreatic exocrine function; low or absent levels can indicate pancreatic insufficiency or digestive dysfunction.