- Prolinase (EC 3.4.13.16), also known as proline-specific dipeptidase, is an exopeptidase that catalyzes the hydrolysis of dipeptides with N-terminal proline residues, releasing free proline and the adjacent amino acid. It plays a complementary role to prolidase, which acts on dipeptides with C-terminal proline. Together, these enzymes contribute to the complete degradation of proline-containing peptides that are resistant to cleavage by many other proteases due to proline’s unique cyclic structure.
- Prolinase is typically found in the cytosol of various mammalian tissues and is most active under neutral to slightly alkaline pH conditions. It is a metallopeptidase, requiring metal ions (often Mn²⁺ or Zn²⁺) as cofactors for enzymatic activity. The enzyme recognizes the N-terminal proline in dipeptides such as Pro-Xaa, where “Xaa” represents any amino acid, and cleaves the peptide bond between them.
- The physiological significance of prolinase lies in its role in protein and peptide catabolism, especially in the breakdown of dietary and endogenous proteins rich in proline. Since proline-rich peptides are common in collagen and other structural proteins, prolinase activity contributes to the turnover of extracellular matrix components, nutrient absorption, and proline recycling, which is important for collagen resynthesis and energy metabolism.
- Although less well-characterized than prolidase, prolinase has been identified in liver, kidney, and intestinal tissues, suggesting its role in amino acid salvage pathways and nutrient processing. Dysregulation of proline metabolism, including enzymes like prolinase, is associated with certain metabolic disorders, fibrotic conditions, and nutritional deficiencies.
- In summary, prolinase is a proline-specific dipeptidase that hydrolyzes dipeptides with N-terminal proline, facilitating the efficient metabolism of proline-rich proteins. It serves a vital role in maintaining amino acid balance and supporting tissue repair and metabolic homeostasis.
