Prolyl carboxypeptidase (PRCP) is structurally related to dipeptidyl peptidase 2 and shares with it the ability to cleave peptides C-terminal to proline. PRCP is the latest addition to our panel of peptidases.
Prolylcarboxypeptidase (PRCP, E.C.22.214.171.124), a serine protease, cleaves off C-terminal amino acid residues adjacent to a proline. It is found in the central nervous system, but also in peripheral tissues such as the kidney, lung and liver.
The enzyme was first named angiotensinase C because of its ability to convert the vasoconstrictive angiotensin II to angiotensin 1-7, which causes vasodilatation. It was also shown to inactivate angiotensin III and truncate α-melanocyte stimulating hormone 1-13 (α-MSH 1-13). The latter is an anorexigenic neuromodulator which plays an important role in the regulation of food intake and body weight. Truncation of this hormone by PRCP results in an inactive form called α-MSH 1-12, which does not evoke satiety.
This effect is believed to take place at the site of hypothalamic neurons. However, recent studies showed that treatment of experimental animals with small molecule PRCP inhibitors that act peripherally, decreased food intake. Further investigation of the functions of peripheral PRCP and its role in body weight regulation is necessary.
Therefore, validated assays to measure PRCP activity are indispensable. The lack of well-validated assay methods may be at least partly responsible for the limited knowledge on PRCP activity in different biological samples.
We are currently optimizing and validating two different in-house methods, using Z-Pro-Phe as substrate, for linearity, specificity, accuracy, intra-and interday precision, limit of detection, and limit of quantitation.