Prolylcarboxypeptidase (PRCP, E.C.3.4.16.2), 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, placenta, 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, facilitate the autoactivation of prekallikrein and truncate des-Arg9-bradykinin and 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. These findings suggested that besides the centrally active α-MSH 1-13, PRCP can also truncate peripherally acting peptides involved in body weight regulation. The search for other candidate substrates led to the identification of pyroglutamated apelin-13 ((pyr)-apelin-13) as a novel in vitro substrate for PRCP [1].
We aim to contribute to a better understanding of PRCP’s role in obesity by investigating its effect on the cleavage of apelin and its ability to become a therapeutic target in the fight against obesity. We are currently characterizing the cleavage of (pyr)-apelin-13 in a cell culture environment and we will investigate whether truncation by PRCP alters the function of apelin.
We have an in-house, validated RP-HPLC method to measure PRCP activity in different biological samples [2] and are able to produce recombinant human PRCP. Both are valuable tools suitable for exploring the physiological role of PRCP.
Literature
- Kehoe K, Van Elzen R, Verkerk R, et al. Prolyl carboxypeptidase purified from human placenta: its characterization and identification as an apelin-cleaving enzyme. Biochim Biophys Acta - Proteins Proteomics 1864:1481–1488 (2016).
- Kehoe K, Verkerk R, Sim Y, et al. Validation of a specific prolylcarboxypeptidase activity assay and its suitability for plasma and serum measurements. Anal Biochem 443:232–239 (2013).