Colipase

Colipase is a protein cofactor required for optimal enzyme activity of pancreatic lipase. It is secreted by the pancreas in an inactive form called procolipase, which is then activated in the small intestine by trypsin, which cleaves a 5 amino acid peptide, enteropeptidase, from the N-terminus of the procolipase molecule, yielding the active colipase.

The primary function of colipase is to anchor pancreatic lipase to the surface of lipid droplets in the duodenum. Pancreatic lipase alone is unable to efficiently hydrolyze dietary triglycerides because it is inhibited by bile salts, which are also present in the small intestine to emulsify fats. Colipase binds to both lipase and the lipid droplet, displacing the bile salts and allowing lipase to access and hydrolyze the triglycerides. This binding creates a complex with lipase, allowing the enzyme to function effectively in the presence of bile salts.

Specifically, colipase binds to a non-catalytic domain of lipase and to the surface of the lipid emulsion. This interaction stabilizes the lipase at the oil-water interface, overcoming the inhibitory effect of bile salts. The lipase then hydrolyzes triglycerides into monoglycerides and free fatty acids, which are subsequently absorbed by the enterocytes.

Colipase deficiency is rare but can lead to fat malabsorption and steatorrhea (excessive fat in the feces).