Disease relevance of PEMT

• To evaluate the functional significance of PEMT localization, hepatoma cell lines were generated that stably expressed either ER- or Golgi-localized PEMT only [1].
• For both cell types, the Km and specific activity of PEMT were comparable in normal and cystic fibrosis samples [2].
• Several lines of evidence suggested that PEMT2 might have a role in hepatocyte proliferation and liver cancer [3].
• Similarly, phosphatidylethanolamine methyltransferase (PEMT) activity, which is important for hepatic phosphatidylcholine (PC) synthesis, is also depressed in alcoholic liver disease, therefore calling for the administration of the products of the reaction [4].
• PEMT as described is safe for domiciliary use and this study suggests that PEMT has a beneficial effect in the management of the acute whiplash injury [5].

Psychiatry related information on PEMT

• Activity of phosphatidylethanolamine-N-methyltransferase in brain affected by Alzheimer's disease [6].
• The degree of decrease in PNMT activity in the hippocampus correlated significantly with the degree of dementia [7].
• Given the importance of the swine (Sus scrofa) as an animal model for human development, physiology and disease, neurons containing the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT), were mapped in the medulla oblongata of neonatal swine as a first step in identifying their roles in central autonomic control [8].

High impact information on PEMT

• Recently we and others have demonstrated that various preparations of mammalian brain contain enzymes, the phosphatidylethanolamine N-methyltransferase (PeMT), which catalyse the synthesis of phosphatidylcholine (PC), using S-adenosylmethionine (SAM) as a methyl donor for the stepwise methylation of phosphatidylethanolamine (PE) [9].
• PNMT and/or NMT activity were present in red blood cells (RBCs), and cancer cell lines [10].
• PNMT activity in a human bronchial epithelial cell line was dramatically increased by incubation with dexamethasone [10].
• Human kidney, lung, and pancreas showed immunohistochemical staining with an antibody to adrenal PNMT [10].
• RBC PNMT activity was lower in males than females and was increased in hyperthyroidism and decreased in hypothyroidism [10].

Chemical compound and disease context of PEMT

• Therefore, the hypothesis that reduced PEMT activity accounts for the impaired coupling of beta-adrenergic receptor to adenylate cyclase in lymphocytes and granulocytes in cystic fibrosis is rejected [2].
• It is plausible that the decreased activity of phosphatidylethanolamine-N-methyltransferase and its low compensating ability could relate to the modification of phosphatidylcholine in brain tissues from Alzheimer's disease patients [6].
• In the ventrolateral medulla, from the level of the obex to 11 mm rostral to the obex where the C1 group of neurons is located, there were 7,631 +/- 844 PNMT-positive neurons in control brains and 3,604 +/- 1,051 in brains affected by Parkinson's disease (47% of control) [11].
• Our results demonstrate a selective loss of C1 and C3 PNMT-positive neurons, providing the first quantitative evidence for damage to these presumed brainstem sympathetic premotor neurons in Parkinson's disease [11].
• The above differences in clinical presentation were largely explained by lower total tissue contents of catecholamines and expression of TH and negligible stores of epinephrine and expression of PNMT in pheochromocytomas from VHL than from MEN 2 patients [12].

Biological context of PEMT

• A targeting vector that interrupts exon 2 was constructed and introduced into mice yielding three genotypes: normal (+/+), heterozygotes (+/-), and homozygotes (-/-) for the disrupted PEMT gene [13].
• Phosphatidylethanolamine N-methyltransferase (PEMT) is a quatrotopic membrane protein that catalyzes the conversion of phosphatidylethanolamine to phosphatidylcholine through three sequential methylation reactions [14].
• Bioinformatic analysis of the predicted amino acid sequence of human PEMT identified two putative AdoMet-binding motifs (98GXG100 and 180EE181) [14].
• To assess the importance of PEMT localization for Hcy homeostasis, we identified and ablated the minimal ER targeting motif [1].
• Mutagenesis of a conserved, C-terminal lysine residue (197) relocalized the enzyme to the Golgi, demonstrating that Lys-197 is essential for targeting PEMT to the ER [1].

Anatomical context of PEMT

• The PEMT pathway is a metabolically channeled process localized to the endoplasmic reticulum (ER) [1].
• Our previous reports implicated PEMT in the regulation of hepatocyte growth and transformation [15].
• Furthermore, each of the three PEMT transcripts is present in varying abundance in liver whereas heart and testis contain only one and two transcripts, respectively [16].
• Phosphatidylethanolamine N-methyltransferase in human red blood cell membrane preparations. Kinetic mechanism [17].
• Screening of somatic cell hybrid panels, radiation hybrid panel mapping and fluorescent in situ hybridization mapping localized the human gene for PEMT2 to chromosome 17p11 [3].

Associations of PEMT with chemical compounds

• The active form of CTP:phosphocholine cytidylyltransferase, the regulated enzyme in the CDP-choline pathway, was increased 60% in the PEMT-deficient mice [13].
• This experiment also demonstrated that the choline moiety derived from PEMT in the liver can be distributed via the plasma throughout the mouse where it is found as phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin [13].
• A model positions two separate AdoMet-binding motifs of PEMT in close proximity at the external leaflet of the endoplasmic reticulum membrane [14].
• Phosphatidylethanolamine N-methyltransferase (PEMT) catalyzes each transmethylation reaction, and S-adenosylmethionine is the methyl group donor [18].
• Analysis of mice lacking a functional PEMT gene revealed a severe reduction in plasma homocysteine levels [14].

Other interactions of PEMT

• Human lymphocyte and granulocyte membranes contain an enzyme, phosphatidylethanolamine N-methyltransferase (PEMT), which catalyzes the transfer of a methyl group from S-adenosylmethionine to the polar head group of phosphatidylethanolamine to form phosphatidylmonomethylethanolamine [2].
• A SNP in the PEMT coding region (+5465 G-->A; rs7946) and a betaine:homocysteine methyltransferase (BHMT) SNP (+742 G-->A; rs3733890) were not associated with susceptibility to choline deficiency [19].
• Concentrations of triacylglycerols and cholesterol in plasma and lipoproteins, concentration of homocysteine in plasma, concentration of cholesterol in liver, fecal lipid excretion, expression of hepatic HMG-CoA reductase, phosphatidylethanolamine N-methyltransferase 2 (PEMT-2) and of LDL receptor were measured [20].
• Labeled precursor incorporation experiments have shown that phosphatidylserine decarboxylase and phosphatidylethanolamine N-methyltransferase are more active in cells infected by E. cuniculi than in uninfected cells [21].

Analytical, diagnostic and therapeutic context of PEMT

• Site-directed mutagenesis experiments demonstrated the requirement for the conserved motifs in PEMT specific activity [14].
• Molecular dissection of the S-adenosylmethionine-binding site of phosphatidylethanolamine N-methyltransferase [14].
• METHODS: The status of the PEMPT gene and PEMT2 mRNA expression were evaluated with Southern and Northern blotting, respectively, in HCC and the noninvolved liver [15].
• Streak artefacts in PEMT for large detector rotation increments led to the development of an expression for the maximum rotation increment that maintains complete angular sampling [22].
• By chance movement scores for the PEMT group were significantly worse at entry to the study than the control group (p less than 0.05) [5].

References