KPV (Lys-Pro-Val) vs MOTS-c

KPV (Lys-Pro-Val)

KPV is the tripeptide lysine–proline–valine, corresponding to the last three residues of alpha-melanocyte-stimulating hormone (α-MSH). It lacks the His-Phe-Arg-Trp core sequence through which α-MSH activates melanocortin receptors, so its pharmacology cannot be assumed to match that of the parent hormone. Interest in it follows reports that C-terminal fragments of α-MSH alter inflammatory signalling in cell and animal models. Published studies are mainly in cultured epithelial and immune cells and in mouse models of chemically induced colitis. The literature is small, and human data are scarce.

MOTS-c

MOTS-c is a 16-residue peptide encoded by a short open reading frame within the mitochondrial gene for 12S ribosomal RNA. It belongs to the mitochondrial-derived peptides, a small group that also includes humanin, which is encoded in the 16S rRNA gene. Since it was first described in the mid-2010s it has been studied mainly in cultured cells and in mice, with attention to glucose and lipid handling in skeletal muscle and to cellular responses to metabolic stress. Human data are limited and consist mostly of measurements of its circulating levels in observational studies.

How KPV (Lys-Pro-Val) acts

How KPV acts has not been settled. Cell studies have reported that it lowers activation of the transcription factor NF-κB and reduces expression of inflammatory cytokines in intestinal epithelial and immune cell lines. In intestinal epithelial cells, uptake through the di- and tripeptide transporter PepT1 has been reported, which would allow it to act inside the cell rather than at a surface receptor. Whether it also signals through melanocortin receptors such as MC1R is disputed, since reports differ and its sequence lacks the usual receptor-binding motif. The mechanistic work is limited and comes largely from cell and rodent models.

How MOTS-c acts

The first cell and mouse studies reported that MOTS-c inhibits the folate pathway and, with it, de novo purine synthesis, so that the purine intermediate AICAR accumulates. This nucleotide mimics AMP and activates AMP-activated protein kinase (AMPK), a sensor of cellular energy status. Later work reported that under metabolic or oxidative stress the peptide moves from the cytoplasm into the nucleus, where it associates with transcription factors including NRF2 and alters the expression of stress-response genes. Most of this mechanistic evidence comes from cell and rodent models, and human mechanistic data are scarce.

The records side by side

• Type: KPV (Lys-Pro-Val), Tripeptide (alpha-MSH fragment); MOTS-c, Mitochondrial-derived peptide (MDP)
• Length: KPV (Lys-Pro-Val), not recorded; MOTS-c, 16 amino acids
• Molecular weight: KPV (Lys-Pro-Val), not recorded; MOTS-c, 2174.6 g/mol
• Molecular formula: KPV (Lys-Pro-Val), not recorded; MOTS-c, C101H152N28O22S2

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.