PM20D1

Description

The PM20D1 (peptidase M20 domain containing 1) is a protein-coding gene located on chromosome 1.

PM20D1, also known as Peptidase M20 domain containing 1, is a circulating enzyme encoded by the PM20D1 gene in humans. It regulates bioactive N-acyl amide lipids and has been implicated in obesity, type 2 diabetes, pain, and Alzheimer's disease. PM20D1 catalyzes the biosynthesis of N-fatty acyl amino acids from free fatty acids and free amino acids, playing a role in the generation of potent bioactive lipid metabolites from two abundant cellular energy precursors. This enzyme is involved in energy homeostasis, with high expression and secretion into the blood by brown fat in mice. Its expression in adipose tissues increases following cold exposure. Elevated circulating PM20D1 levels in mice lead to accumulation of multiple circulating N-acyl amino acid species and a hypermetabolic phenotype. Conversely, PM20D1 knockout mice exhibit bidirectional dysregulation of circulating N-acyl amino acids, insulin resistance, and glucose intolerance. N-fatty acyl amino acids function as UCP1-independent uncouplers of mitochondrial respiration, contributing to their role in energy homeostasis.

PM20D1 is a secreted enzyme that regulates the levels of N-fatty acyl amino acids (NAAs) in tissues and circulation. It functions as a bidirectional NAA synthase/hydrolase, condensing free fatty acids and free amino acids to generate NAAs and catalyzing the reverse hydrolysis reaction. Some NAAs produced by PM20D1 stimulate oxidative metabolism via mitochondrial uncoupling, increasing energy expenditure in a UPC1-independent manner. This suggests that PM20D1 may indirectly regulate whole body energy expenditure. PM20D1 circulates in tight association with both low- and high-density lipoprotein particles (LDL and HDL).

PM20D1 is also known as Cps1.

Associated Diseases

WES Whole Exome Sequencing