Peptidase M20 domain containing 1 is a circulating enzyme of the mammalian M20 peptidase family. It is encoded by the PM20D1 gene.[1] PM20D1 catalyzes the synthesis of N-acyl amino acids from free fatty acids and free amino acids as well as the reverse hydrolytic reaction.[2] PM20D1, along with FAAH, constitute the two dominant mammalian enzymes that physiologically regulate the fatty acid amide family of signaling metabolites.
In mice, PM20D1 is highly expressed in liver, kidney, small intestine, and brown fat. Its expression in adipose tissues is increased under hypermetabolic conditions. Genetic elevation of circulating PM20D1 in mice leads to accumulation of multiple circulating N-acyl amino acid species and a hypermetabolic phenotype.[2] PM20D1-KO mice exhibit a bidirectional dysregulation of a distinct set of circulating N-acyl amino acids and range of phenotypes, including insulin resistance, altered body temperature in cold, and anti-nociceptive behaviors to inflammatory pain.[3]
Clinical significance
In humans, the PM20D1 locus has been associated with Alzheimer's disease. Elevation of brain PM20D1 is neuroprotective in rodent models of AD.[4]
↑ 2.02.1Long JZ, Svensson KJ, Bateman LA, Lin H, Kamenecka T, Lokurkar IA, et al. (July 2016). "The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria". Cell. 166 (2): 424–435. doi:10.1016/j.cell.2016.05.071. PMID27374330.
↑Long JZ, Roche AM, Berdan CA, Louie SM, Roberts AJ, Svensson KJ, et al. (July 2018). "N-acyl amino acid control of metabolism and nociception". Proceedings of the National Academy of Sciences of the United States of America. 115 (29): E6937–E6945. doi:10.1073/pnas.1803389115. PMID29967167.
↑Sanchez-Mut JV, Heyn H, Silva BA, Dixsaut L, Garcia-Esparcia P, Vidal E, et al. (May 2018). "PM20D1 is a quantitative trait locus associated with Alzheimer's disease". Nature Medicine. 24 (5): 598–603. doi:10.1038/s41591-018-0013-y. PMID29736028.
