- Prolidase (also known as peptidase D or proline dipeptidase) is a cytosolic metallopeptidase that specifically cleaves dipeptides with C-terminal proline or hydroxyproline residues. It plays a crucial role in collagen metabolism, as proline and hydroxyproline are particularly abundant in collagen, one of the most prevalent structural proteins in mammals. By liberating free proline from imidodipeptides, prolidase contributes to the recycling of proline for collagen resynthesis and other cellular processes.
- The enzyme is manganese-dependent and belongs to the M24 family of metallopeptidases. It functions optimally at neutral to slightly alkaline pH and requires Mn²⁺ ions as cofactors for its catalytic activity. The enzyme’s specificity for proline at the C-terminus is unique, as proline-containing peptides often resist cleavage by many other proteases due to the imino ring structure of proline that restricts backbone flexibility.
- Prolidase is expressed in various tissues, with high activity in organs involved in active collagen turnover, such as the skin, kidneys, liver, and connective tissues. It is especially important in wound healing, tissue remodeling, and fibrogenesis, where proline availability is rate-limiting for collagen biosynthesis.
- Deficiency in prolidase activity is associated with a rare autosomal recessive disorder known as prolidase deficiency, characterized by impaired collagen turnover, chronic skin ulcers, recurrent infections, developmental delays, and in some cases, intellectual disability. This condition highlights the enzyme’s essential role in maintaining tissue integrity and cellular homeostasis.
- In clinical research and diagnostics, prolidase activity can be used as a biomarker for diseases involving altered collagen metabolism, such as fibrotic diseases, chronic liver disease, and diabetes-related tissue damage. It is also studied in oncology, as its activity is often dysregulated in various cancers, reflecting the tumor microenvironment’s remodeling needs.
- In summary, prolidase is a specialized metallopeptidase essential for proline recovery and collagen homeostasis. Its biological significance spans tissue repair, development, and disease, making it an important enzyme in both physiological and pathological contexts.
