Phosphatidylethanolamine N-methyltransferase

1040018618ENSG00000133027ENSMUSG00000000301Q9UBM1Q61907NM_001267551NM_001267552NM_007169NM_148172NM_148173NM_001290011NM_001290012NM_001290013NM_001290014NM_008819NP_001254480NP_001254481NP_009100NP_680477NP_680478NP_001276940NP_001276941NP_001276942NP_001276943NP_032845Phosphatidylethanolamine N-methyltransferase (abbreviated PEMT) is a transferase enzyme (EC 2.1.1.17) which converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC) in the liver.

The PEMT enzyme converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC) via three sequential methylations by S-adenosyl methionine (SAM).

[16] The exact mechanism by which PEMT catalyzes the sequential methylation of PE by three molecules of SAM to form PC remains unknown.

It is suspected that the structure or specific conformation adopted by PE has a lower affinity for the PEMT active site; consequently, upon methylation, PMME would be immediately converted to PDME and PDME to PC, via a Bi-Bi or ping-pong mechanism before another PE molecule could enter the active site.

[20] Although the enzymatic structure is unknown, PEMT is proposed to contain four hydrophobic membrane-spanning regions, with both its C and N termini on the cytosolic side of the ER membrane.

[21] PEMT activity is unrelated to enzyme mass, but rather is regulated by supply of substrates including PE, as well as PMME, PDME, and SAM.

Ablation of the estrogen binding site in the PEMT promoter region may increase risk of hepatic steatosis from choline deficiency.

[10][26][27][28] A Val-to-Met substitution at residue 175, leading to reduced PEMT activity, has been linked to non-alcoholic fatty liver disease.

[30] A single-nucleotide polymorphism (G to C) in the promoter region of the PEMT has been demonstrated to contribute to development of organ dysfunction in conjunction with a low-choline diet.

[36] The PEMT deficient mice showed elevated plasma glucagon levels, increased hepatic expression of glucagon receptor, phosphorylated AMP-activated protein kinase (AMPK), and serine-307-phosphorylated insulin receptor substrate 1 (IRS1-s307), which blocks insulin-mediated signal transduction; together, these contribute to enhanced gluconeogenesis and ultimately insulin resistance.