preproenzymes

Preproenzymes are the initial gene products of enzymes that carry two regulatory segments at the N-terminus: a signal peptide (the pre) and a propeptide (the pro). This combination keeps the polypeptide inactive and directs it to the secretory pathway. After synthesis, the signal peptide is removed in the endoplasmic reticulum, yielding a proenzyme that remains inactive until the propeptide is cleaved by specific proteases to form the mature enzyme.

Activation typically occurs through proteolytic processing in a controlled sequence, either during transit through the secretory pathway or after secretion into a target site such as the digestive lumen. The propeptide often assists folding or stability, and its removal relieves autoinhibition to generate catalytic activity.

Examples include pepsinogen (activated to pepsin in the stomach) and the pancreatic zymogens trypsinogen and chymotrypsinogen (activated to trypsin and chymotrypsin in the intestine) by specific convertases like enteropeptidase. Other examples are proelastase and procarboxypeptidases A and B, activated in pancreatic juice.

Significance: the preproenzyme architecture enables safe intracellular synthesis and targeted activation, preventing premature proteolysis. The terminology varies; some authors use preproenzyme to denote any inactive precursor, while others reserve it for precursors that include both a signal and a pro segment. Misprocessing can contribute to disease, underscoring the importance of regulated proteolysis in physiology.