Abstract
Prolidase (peptidase D), encoded by the PEPD gene, is a ubiquitously expressed cytosolic metalloproteinase, the only enzyme capable of cleaving imidodipeptides containing C-terminal proline or hydroxyproline. Prolidase catalyzes the rate-limiting step during collagen recycling and is essential in protein metabolism, collagen turnover, and matrix remodeling. Prolidase, therefore plays a crucial role in several physiological processes such as wound healing, inflammation, angiogenesis, cell proliferation, and carcinogenesis. Accordingly, mutations leading to loss of prolidase catalytic activity result in prolidase deficiency a rare autosomal recessive metabolic disorder characterized by defective wound healing. In addition, alterations in prolidase enzyme activity have been documented in numerous pathological conditions, making prolidase a useful biochemical marker to measure disease severity. Furthermore, recent studies underscore the importance of a non-enzymatic role of prolidase in cell regulation and infectious disease. This review aims to provide comprehensive information on prolidase, from its discovery to its role in health and disease, while addressing the current knowledge gaps.
Highlights
Prolidase is the only dipeptidase known to catalyze the hydrolysis of a dipeptide containing a C-terminal proline or hydroxyproline into constituent amino acids (Endo et al, 1989; Kitchener and Grunden 2012) (Figure 1)
Prolidase Deficiency (PD) is a rare autosomal recessive disorder marked by elevated levels of imidodipeptides (Cottin et al, 2020)
The study observed that more advanced stages, higher tumor grades, and higher cancer antigen 125 (CA-125) levels among patients with epithelial ovarian carcinomas (EOC) were associated with higher serum prolidase activity
Summary
Prolidase is the only dipeptidase known to catalyze the hydrolysis of a dipeptide containing a C-terminal proline or hydroxyproline into constituent amino acids (Endo et al, 1989; Kitchener and Grunden 2012) (Figure 1). It has many aliases, including peptidase D (PEPD), Xaa-Pro dipeptidase, X-Pro dipeptidase, proline dipeptidase, or imidodipeptidase. The most studied substrate of prolidase are imidodipeptides that are generated during breakdown of collagen the predominant component of the extracellular matrix (ECM) (Kitchener and Grunden 2012). We start with a historical snapshot of the discovery of prolidase, provide an overview of the current body of research, followed by a discussion of the existing knowledge gaps in prolidase research, and conclude with future prospective
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