Prolylcarboxypeptidase (PRCP) has been known of for decades now, but very recent research into it has shed light on its involvement in the adipostat. PRCP is an enzyme that works by removing something called the C-terminus from the end of an amino acid chain. In layman’s, all amino acids begin with an N-terminus (i.e. an amine group that contains a nitrogen atom, hence the ‘N’) and end with a C-terminus (i.e. a carboxyl group). A chain of amino acids is formed by connecting the N-terminus of one amino acid to the C-terminus of the next, thus giving rise to polypeptides (typically short amino acid chains) and proteins (long amino acid chains). If this is still not clear, think of PRCP as an enzyme that chops the end off a protein, thereby changing its properties and what it can do.
PRCP has so far been found to be involved in regulating blood pressure, but now research coming out of the Yale School of Medicine has connected it with the peptide hormone alpha-melanocyte-stimulating hormone (aMSH). aMSH is heavily involved in the production and release of melanin, a pigment that gives rise to skin color. In fact, two synthetic analogs of aMSH have been developed, one of which is Melanotan which is being sold on the black market quite a lot lately and is the reason that some bodybuilders in your gym look like they’ve been dipped in wood stain. The other has given rise to Bremelanotide, a drug for treating sexual dysfunction that was abandoned last year due to health concerns.
aMSH is also a powerful appetite suppressant hormone in the brain, however the researchers found that its activity is short-lived due to rapid deactivation. While the full picture has yet to be decoded, they did discover that PRCP was responsible for altering the structure of aMSH (by cleaving the C-terminus) rendering it no longer neuroactive. To further investigate this, they inhibited PRCP in mice and discovered that it reduced food intake across the board, even in obese mice. They also found that mice bred deficient in the PRCP gene were naturally leaner despite high calorie intakes. Both groups had higher levels of aMSH in the brain (specifically, the hypothalamus, which is generally considered the food control center of the body) compared to the control group. This research will surely kick off a new avenue of research with regards to helping the obese control their appetites.
Source: Wallingford N, Perroud B, Gao Q, Coppola A, Gyengesi E, Liu ZW, Gao XB, Diament A, Haus KA, Shariat-Madar Z, Mahdi F, Wardlaw SL, Schmaier AH, Warden CH, Diano S. Prolylcarboxypeptidase regulates food intake by inactivating alpha-MSH in rodents. J Clin Invest. 2009 Jul 20.