Pemt, short for phosphatidylethanolamine N-methyltransferase, is a key enzyme that catalyzes the production of phosphatidylcholine, an important phospholipid in cell membranes. This process is part of the phosphatidylcholine synthesis pathway, which is crucial for normal cellular function, especially in maintaining membrane integrity and lipid metabolism [1,2,3]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can be used to study Pemt's functions in vivo.

In mice, reduced expression of hepatic Pemt causes steatosis, inflammation, and fibrosis, suggesting its role in non-alcoholic fatty liver disease (NAFLD) pathogenesis. In humans, common Pemt variants are associated with NAFLD risk, and hepatic Pemt expression decreases with increasing NAFLD severity, especially in postmenopausal women [1]. Also, in the context of hepatitis C virus (HCV) infection, HCV induces Pemt expression, which mediates steatosis and supports virus replication, with higher Pemt expression in genotype 3-infected liver biopsies compared to others [2].

In conclusion, Pemt is essential for phosphatidylcholine synthesis and thus for normal cellular function. Studies using KO/CKO mouse models and human genetic variant analyses have revealed its significant role in liver-related diseases, including NAFLD and HCV-induced steatosis. Understanding Pemt's functions provides insights into the mechanisms of these diseases and may offer potential therapeutic targets.

References:

1. Piras, Ignazio S, Raju, Anish, Don, Janith, Gerhard, Glenn S, DiStefano, Johanna K. 2022. Hepatic PEMT Expression Decreases with Increasing NAFLD Severity. In International journal of molecular sciences, 23, . doi:10.3390/ijms23169296. https://pubmed.ncbi.nlm.nih.gov/36012560/

2. Abomughaid, Mosleh, Tay, Enoch S E, Pickford, Russell, George, Jacob, Douglas, Mark W. 2023. PEMT Mediates Hepatitis C Virus-Induced Steatosis, Explains Genotype-Specific Phenotypes and Supports Virus Replication. In International journal of molecular sciences, 24, . doi:10.3390/ijms24108781. https://pubmed.ncbi.nlm.nih.gov/37240132/

3. Bernhard, Wolfgang. 2020. Choline in cystic fibrosis: relations to pancreas insufficiency, enterohepatic cycle, PEMT and intestinal microbiota. In European journal of nutrition, 60, 1737-1759. doi:10.1007/s00394-020-02358-2. https://pubmed.ncbi.nlm.nih.gov/32797252/