CPA1

CPA1, or carboxypeptidase A1, is a human gene that encodes pancreatic carboxypeptidase A1, a digestive enzyme produced by pancreatic acinar cells. The enzyme is secreted into the small intestine as part of pancreatic juice, where it participates in protein digestion by removing C-terminal amino acids from peptide substrates, with a preference for bulky hydrophobic residues.

The CPA1 protein is synthesized as an inactive zymogen, procarboxypeptidase A1, and is activated in the duodenum by proteolytic processing, typically by trypsin. The mature enzyme is a zinc-dependent exopeptidase, and zinc coordination at the active site is essential for catalytic activity.

Expression of CPA1 is highest in the pancreas, and the enzyme is released into pancreatic juice and functions in the digestive tract. As part of the pancreatic carboxypeptidase family, CPA1 operates alongside other digestive enzymes to facilitate protein breakdown.

Genetics and clinical significance: Variants in CPA1 have been studied in relation to chronic pancreatitis. The common missense variant N34S (asparagine to serine at position 34) has been associated with an increased risk of chronic pancreatitis in several studies. The proposed mechanism often involves misfolding of CPA1 and endoplasmic reticulum stress in pancreatic acinar cells, rather than simply loss of enzymatic activity. Rare CPA1 variants may contribute to disease risk in some individuals, and the overall causal relationship remains an area of ongoing research.