| Phosphatidylethanolamine N-methyltransferase |
| Identifiers |
| EC number |
2.1.1.17 |
| CAS number |
37256-91-0 |
| Databases |
| IntEnz |
IntEnz view |
| BRENDA |
BRENDA entry |
| ExPASy |
NiceZyme view |
| KEGG |
KEGG entry |
| MetaCyc |
metabolic pathway |
| PRIAM |
profile |
| PDB structures |
RCSB PDB PDBe PDBsum |
| Gene Ontology |
AmiGO / EGO |
| Search |
| PMC |
articles |
| PubMed |
articles |
| NCBI |
proteins |
|
Overview of reactions catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT).
| Phosphatidylethanolamine N-methyltransferase |
| Identifiers |
| Symbols |
PEMT ; PEAMT; PEMPT; PEMT2; PNMT |
| External IDs |
OMIM: 602391 MGI: 104535 HomoloGene: 6291 GeneCards: PEMT Gene |
| EC number |
2.1.1.17, 2.1.1.71 |
| Gene ontology |
| Molecular function |
• phosphatidyl-N-methylethanolamine N-methyltransferase activity
• phosphatidylethanolamine N-methyltransferase activity
• phosphatidylethanolamine binding
• phosphatidyl-N-dimethylethanolamine N-methyltransferase activity
|
| Cellular component |
• endoplasmic reticulum membrane
• integral component of membrane
• brush border membrane
• mitochondrial membrane
• sarcolemma
|
| Biological process |
• lipid metabolic process
• phospholipid metabolic process
• phosphatidylcholine biosynthetic process
• cell proliferation
• negative regulation of cell proliferation
• methylation
• response to vitamin
• response to drug
• response to amino acid
• small molecule metabolic process
• response to ethanol
• glycerophospholipid biosynthetic process
• S-adenosylhomocysteine metabolic process
• S-adenosylmethionine metabolic process
• positive regulation of lipoprotein metabolic process
• positive regulation of protein targeting to mitochondrion
|
| Sources: Amigo / QuickGO |
|
| Orthologs |
| Species |
Human |
Mouse |
| Entrez |
10400 |
18618 |
| Ensembl |
ENSG00000133027 |
ENSMUSG00000000301 |
| UniProt |
Q9UBM1 |
Q61907 |
| RefSeq (mRNA) |
NM_001267551 |
NM_001290011 |
| RefSeq (protein) |
NP_001254480 |
NP_001276940 |
| Location (UCSC) |
Chr 17:
17.51 – 17.59 Mb |
Chr 11:
59.97 – 60.05 Mb |
| PubMed search |
[1] |
[2] |
|
|
Phosphatidylethanolamine N-methyltransferase (abbreviated PEMT) is a transferase enzyme (EC 2.1.1.17) which converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC) in the liver.[1][2][3] In humans it is encoded by the PEMT gene within the Smith-Magenis syndrome region on chromosome 17.[4][5]
While the CDP-choline pathway, in which choline obtained either by dietary consumption or by metabolism of choline-containing lipids is converted to PC, accounts for approximately 70% of PC biosynthesis in the liver, the PEMT pathway has been shown to have played a critical evolutionary role in providing PC during times of starvation. Furthermore, PC made via PEMT plays a wide range of physiological roles, utilized in choline synthesis, hepatocyte membrane structure, bile secretion, and very-low-density lipoprotein (VLDL) secretion.[6][7]
Contents
- 1 Nomenclature
- 2 Function
- 3 Mechanism
- 4 Structure
- 5 Regulation
- 6 Disease relevance
- 6.1 Liver
- 6.2 Cardiovascular disease and artherosclerosis
- 6.3 Obesity and insulin resistance
- 7 See also
- 8 References
- 9 Further reading
- 10 External links
Nomenclature
Phosphatidylethanolamine N-methyltransferase is also known as lipid methyl transferase, LMTase, phosphatidylethanolamine methyltransferase, phosphatidylethanolamine-N-methylase, and phosphatidylethanolamine-S-adenosylmethionine-methyltransferase.
Function
The PEMT enzyme converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC) via three sequential methylations by S-adenosyl methionine (SAM). The enzyme is found in endoplasmic reticulum and mitochondria-associated membranes. It accounts for ~30% of PC biosynthesis, with the CDP-choline, or Kennedy, pathway making ~70%.[6] PC, typically the most abundant phospholipid in animals and plants, accounts for more than half of cell membrane phospholipids and approximately 30% of all cellular lipid content. The PEMT pathway is therefore crucial for maintaining membrane integrity.[8]
PC made via the PEMT pathway can be degraded by phospholipases C/D, resulting in the de novo formation of choline. Thus, the PEMT pathway contributes to maintaining brain and liver function and larger-scale energy metabolism in the body.[3][6]
PC molecules produced by PEMT-catalyzed methylation of PE are more diverse, and tend to contain longer chain, polyunsaturated species and more arachidonate, whereas those produced via the CDP-choline pathway are typically composed of medium-length, saturated chains.[9]
A major pathway for hepatic PC utilization is secretion of bile into the intestine.[3] PEMT activity also dictates normal very-low-density lipoprotein (VLDL) secretion by the liver.[10][11] PEMT is also a significant source and regulator of plasma homocysteine, which can be secreted or converted to methionine or cysteine.[12]
Mechanism
The exact mechanism by which PEMT catalyzes the sequential methylation of PE by three molecules of SAM to form PC remains unknown. Kinetic analyses as well as amino acid and gene sequencing have shed some light on how the enzyme works. Studies suggest that a single substrate binding site binds all three phospholipids methylated by PEMT: PE, phosphatidyl-monomethylethanolamine (PMME) and phosphatidyl-dimethylethanolamine. The first methylation, that of PE to PMME, has been shown to be the rate-limiting step in conversion of PE to PC. 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.[3][13][14]
Structure
Purification of PEMT by Neale D. Ridgway and Dennis E. Vance in 1987 produced an 18.3 kDa protein.[15] Subsequent cloning, sequencing, and expression of PEMT cDNA resulted in a 22.3 kDa, 199-amino acid protein.[16] 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. Kinetic studies indicate a common binding site for PE, PMME, and PDME substrates.[3] SAM binding motifs have been identified on both the third and fourth transmembrane sequences. Site-directed mutagenesis has pinpointed the residues Gly98, Gly100, Glu180, and Glu181 to be essential for SAM binding in the active site.[17]
Regulation
PEMT activity is unrelated to enzyme mass, but rather is regulated by supply of substrates including PE, as well as PMME, PDME, and SAM. Low substrate levels inhibit PEMT. The enzyme is further regulated by S-adenosylhomocysteine produced after each methylation.[14][18][19]
PEMT gene expression is regulated by transcription factors including activator protein 1 (AP-1) and Sp1. Sp1 is a negative regulator of PEMT transcription, yet is it is a positive regulator of choline-phosphate cytidylyltransferase (CT) transcription.[3][20] This is one of several examples of the reciprocal regulation of PEMT and CT in the PEMT and CDP-choline pathways. Estrogen has also been shown to be a positive regulator of hepatocyte PEMT transcription. Ablation of the estrogen binding site in the PEMT promoter region may increase risk of hepatic steatosis from choline deficiency.[21]
Disease relevance
Overview of biological roles and regulation of phosphatidylethanolamine N-methyltransferase (PEMT)
Liver
PEMT deficiency in mice, genetically induced by PEMT gene knockout, produced minimal effect on PE and PC levels. However, upon being fed a choline-deficient diet, the mice developed severe liver failure. Rapid PC depletion due to biliary PC secretion, as well as protein leakage from loss of membrane integrity due to lowered PC/PE ratios, led to steatosis and steatohepatitis.[6][22][23][24]
A Val-to-Met substitution at residue 175, leading to reduced PEMT activity, has been linked to non-alcoholic fatty liver disease.[25] This substitution has also been linked to increased frequency of non-alcoholic steatohepatitis.[26]
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.[27]
Cardiovascular disease and artherosclerosis
PEMT modulates levels of blood plasma homocysteine, which is either secreted or converted to methionine or cysteine. High levels of homocysteine are linked to cardiovascular disease and artherosclerosis, particularly coronary artery disease.[28] PEMT deficiency prevents artherosclerosis in mice fed high-fat, high-cholesterol diets.[29] This is largely a result of lower levels of VLDL lipids in the PEMT-deficient mice.[30] Furthermore, the decreased lipid (PC) content in VLDLs causes changes in lipoprotein structure which allow them to be cleared more rapidly in the PEMT-deficient mice.[3]
Obesity and insulin resistance
PEMT-deficient mice fed high-fat diets have been shown to resist weight gain and be protected from insulin resistance. One potential reason for this phenomenon is that these mice, which exhibit hypermetabolic behavior, rely more on glucose than on fats for energy.[31] It was concluded that insufficient choline resulted in the lack of weight gain, supported by the fact that PC produced via the PEMT pathway can be used to form choline.[32]
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.[33] Another possibility is that lack of PEMT in adipose tissue may affect normal fat deposition.[34]
See also
References
- ^ Vance DE, Li Z, Jacobs RL (Nov 2007). "Hepatic phosphatidylethanolamine N-methyltransferase, unexpected roles in animal biochemistry and physiology". The Journal of Biological Chemistry 282 (46): 33237–41. doi:10.1074/jbc.R700028200. PMID 17881348.
- ^ "EC 2.1.1.17". International Union of Biochemistry and Molecular Biology Nomenclature. School of Biological and Chemical Sciences, Queen Mary, University of London. 17 February 2014. Retrieved 25 February 2014.
- ^ a b c d e f g Vance DE (Mar 2013). "Physiological roles of phosphatidylethanolamine N-methyltransferase". Biochimica et Biophysica Acta 1831 (3): 626–32. doi:10.1016/j.bbalip.2012.07.017. PMID 22877991.
- ^ "Entrez Gene: PEMT".
- ^ Walkey CJ, Shields DJ, Vance DE (Jan 1999). "Identification of three novel cDNAs for human phosphatidylethanolamine N-methyltransferase and localization of the human gene on chromosome 17p11.2". Biochimica et Biophysica Acta 1436 (3): 405–12. doi:10.1016/s0005-2760(98)00147-7. PMID 9989271.
- ^ a b c d Vance DE (Jun 2014). "Phospholipid methylation in mammals: from biochemistry to physiological function". Biochimica et Biophysica Acta 1838 (6): 1477–87. doi:10.1016/j.bbamem.2013.10.018. PMID 24184426.
- ^ Jackowski S, Fagone P (Jan 2005). "CTP: Phosphocholine cytidylyltransferase: paving the way from gene to membrane". The Journal of Biological Chemistry 280 (2): 853–6. doi:10.1074/jbc.R400031200. PMID 15536089.
- ^ Christie, William W., ed. (16 September 2013). "Phosphatidylcholine and Related Lipids". AOCS Lipid Library. AOCS. Retrieved 13 February 2014.
- ^ DeLong CJ, Shen YJ, Thomas MJ, Cui Z (Oct 1999). "Molecular distinction of phosphatidylcholine synthesis between the CDP-choline pathway and phosphatidylethanolamine methylation pathway". The Journal of Biological Chemistry 274 (42): 29683–8. doi:10.1074/jbc.274.42.29683. PMID 10514439.
- ^ Yao ZM, Vance DE (Feb 1988). "The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes". The Journal of Biological Chemistry 263 (6): 2998–3004. PMID 3343237.
- ^ Vance JE, Vance DE (Aug 1985). "The role of phosphatidylcholine biosynthesis in the secretion of lipoproteins from hepatocytes". Canadian Journal of Biochemistry and Cell Biology = Revue Canadienne De Biochimie Et Biologie Cellulaire 63 (8): 870–81. doi:10.1139/o85-108. PMID 3904950.
- ^ Refsum H, Ueland PM, Nygård O, Vollset SE (1998). "Homocysteine and cardiovascular disease". Annual Review of Medicine 49: 31–62. doi:10.1146/annurev.med.49.1.31. PMID 9509248.
- ^ Ridgway ND, Vance DE (Nov 1988). "Kinetic mechanism of phosphatidylethanolamine N-methyltransferase". The Journal of Biological Chemistry 263 (32): 16864–71. PMID 3182819.
- ^ a b Ridgway ND, Yao Z, Vance DE (Jan 1989). "Phosphatidylethanolamine levels and regulation of phosphatidylethanolamine N-methyltransferase". The Journal of Biological Chemistry 264 (2): 1203–7. PMID 2910850.
- ^ Ridgway ND, Vance DE (Dec 1987). "Purification of phosphatidylethanolamine N-methyltransferase from rat liver". The Journal of Biological Chemistry 262 (35): 17231–9. PMID 3680298.
- ^ Cui Z, Vance JE, Chen MH, Voelker DR, Vance DE (Aug 1993). "Cloning and expression of a novel phosphatidylethanolamine N-methyltransferase. A specific biochemical and cytological marker for a unique membrane fraction in rat liver". The Journal of Biological Chemistry 268 (22): 16655–63. PMID 8344945.
- ^ Shields DJ, Altarejos JY, Wang X, Agellon LB, Vance DE (Sep 2003). "Molecular dissection of the S-adenosylmethionine-binding site of phosphatidylethanolamine N-methyltransferase". The Journal of Biological Chemistry 278 (37): 35826–36. doi:10.1074/jbc.M306308200. PMID 12842883.
- ^ Sundler R, Akesson B (May 1975). "Regulation of phospholipid biosynthesis in isolated rat hepatocytes. Effect of different substrates". The Journal of Biological Chemistry 250 (9): 3359–67. PMID 1123345.
- ^ Vance DE, Ridgway ND (1988). "The methylation of phosphatidylethanolamine". Progress in Lipid Research 27 (1): 61–79. doi:10.1016/0163-7827(88)90005-7. PMID 3057511.
- ^ Cole LK, Vance DE (Apr 2010). "A role for Sp1 in transcriptional regulation of phosphatidylethanolamine N-methyltransferase in liver and 3T3-L1 adipocytes". The Journal of Biological Chemistry 285 (16): 11880–91. doi:10.1074/jbc.M110.109843. PMC 2852925. PMID 20150657.
- ^ Resseguie ME, da Costa KA, Galanko JA, Patel M, Davis IJ, Zeisel SH (Jan 2011). "Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction". The Journal of Biological Chemistry 286 (2): 1649–58. doi:10.1074/jbc.M110.106922. PMC 3020773. PMID 21059658.
- ^ Walkey CJ, Yu L, Agellon LB, Vance DE (Oct 1998). "Biochemical and evolutionary significance of phospholipid methylation". The Journal of Biological Chemistry 273 (42): 27043–6. doi:10.1074/jbc.273.42.27043. PMID 9765216.
- ^ Smit JJ, Schinkel AH, Oude Elferink RP, Groen AK, Wagenaar E, van Deemter L, Mol CA, Ottenhoff R, van der Lugt NM, van Roon MA (Nov 1993). "Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease". Cell 75 (3): 451–62. doi:10.1016/0092-8674(93)90380-9. PMID 8106172.
- ^ Li Z, Agellon LB, Allen TM, Umeda M, Jewell L, Mason A, Vance DE (May 2006). "The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis". Cell Metabolism 3 (5): 321–31. doi:10.1016/j.cmet.2006.03.007. PMID 16679290.
- ^ Song J, da Costa KA, Fischer LM, Kohlmeier M, Kwock L, Wang S, Zeisel SH (Aug 2005). "Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD)". FASEB Journal 19 (10): 1266–71. doi:10.1096/fj.04-3580com. PMC 1256033. PMID 16051693.
- ^ Zeisel, S. H. (2006). "People with fatty liver are more likely to have the PEMT rs7946 SNP, yet populations with the mutant allele do not have fatty liver". The FASEB Journal 20 (12): 2181–2182. doi:10.1096/fj.06-1005ufm.
- ^ da Costa KA, Kozyreva OG, Song J, Galanko JA, Fischer LM, Zeisel SH (Jul 2006). "Common genetic polymorphisms affect the human requirement for the nutrient choline". FASEB Journal 20 (9): 1336–44. doi:10.1096/fj.06-5734com. PMC 1574369. PMID 16816108.
- ^ Robinson, Killian H. (2001). "Homocysteine and coronary artery disease". In Carmel, Ralph; Jacobsen, Ralph Carmel. Homocysteine in Health and Disease. Cambridge: Cambridge University Press. pp. 371–383.
- ^ Zhao Y, Su B, Jacobs RL, Kennedy B, Francis GA, Waddington E, Brosnan JT, Vance JE, Vance DE (Sep 2009). "Lack of phosphatidylethanolamine N-methyltransferase alters plasma VLDL phospholipids and attenuates atherosclerosis in mice". Arteriosclerosis, Thrombosis, and Vascular Biology 29 (9): 1349–55. doi:10.1161/ATVBAHA.109.188672. PMID 19520976.
- ^ Noga AA, Zhao Y, Vance DE (Nov 2002). "An unexpected requirement for phosphatidylethanolamine N-methyltransferase in the secretion of very low density lipoproteins". The Journal of Biological Chemistry 277 (44): 42358–65. doi:10.1074/jbc.M204542200. PMID 12193594.
- ^ Jacobs RL, Zhao Y, Koonen DP, Sletten T, Su B, Lingrell S, Cao G, Peake DA, Kuo MS, Proctor SD, Kennedy BP, Dyck JR, Vance DE (Jul 2010). "Impaired de novo choline synthesis explains why phosphatidylethanolamine N-methyltransferase-deficient mice are protected from diet-induced obesity". The Journal of Biological Chemistry 285 (29): 22403–13. doi:10.1074/jbc.M110.108514. PMC 2903412. PMID 20452975.
- ^ Zeisel, Steven H. (1987). "Phosphatidylcholine: Endogenous Precursor of Choline". In Hanin, Israel; Ansell, Gordon Brian. Lecithin: Technological, Biological and Therapeutic Aspects. New York: Plenum Press. pp. 107–120.
- ^ Wu G, Zhang L, Li T, Zuniga A, Lopaschuk GD, Li L, Jacobs RL, Vance DE (Jan 2013). "Choline supplementation promotes hepatic insulin resistance in phosphatidylethanolamine N-methyltransferase-deficient mice via increased glucagon action". The Journal of Biological Chemistry 288 (2): 837–47. doi:10.1074/jbc.M112.415117. PMC 3543033. PMID 23179947.
- ^ Hörl G, Wagner A, Cole LK, Malli R, Reicher H, Kotzbeck P, Köfeler H, Höfler G, Frank S, Bogner-Strauss JG, Sattler W, Vance DE, Steyrer E (May 2011). "Sequential synthesis and methylation of phosphatidylethanolamine promote lipid droplet biosynthesis and stability in tissue culture and in vivo". The Journal of Biological Chemistry 286 (19): 17338–50. doi:10.1074/jbc.M111.234534. PMC 3089575. PMID 21454708.
Further reading
- Hirata F, Viveros OH, Diliberto EJ, Axelrod J (Apr 1978). "Identification and properties of two methyltransferases in conversion of phosphatidylethanolamine to phosphatidylcholine". Proceedings of the National Academy of Sciences of the United States of America 75 (4): 1718–21. doi:10.1073/pnas.75.4.1718. PMC 392410. PMID 25437.
- Morgan TE (Mar 1969). "Isolation and characterization of lipid N-methylrtansferase from dog lung". Biochimica et Biophysica Acta 178 (1): 21–34. doi:10.1016/0005-2744(69)90128-4. PMID 5773456.
- Schneider WJ, Vance DE (May 1979). "Conversion of phosphatidylethanolamine to phosphatidylcholine in rat liver. Partial purification and characterization of the enzymatic activities". The Journal of Biological Chemistry 254 (10): 3886–91. PMID 438165.
- Zemunik T, Boban M, Lauc G, Janković S, Rotim K, Vatavuk Z, Bencić G, Dogas Z, Boraska V, Torlak V, Susac J, Zobić I, Rudan D, Pulanić D, Modun D, Mudnić I, Gunjaca G, Budimir D, Hayward C, Vitart V, Wright AF, Campbell H, Rudan I (Feb 2009). "Genome-wide association study of biochemical traits in Korcula Island, Croatia". Croatian Medical Journal 50 (1): 23–33. doi:10.3325/cmj.2009.50.23. PMC 2657564. PMID 19260141.
- Mostowska A, Hozyasz KK, Wojcicki P, Dziegelewska M, Jagodzinski PP (Dec 2010). "Associations of folate and choline metabolism gene polymorphisms with orofacial clefts". Journal of Medical Genetics 47 (12): 809–15. doi:10.1136/jmg.2009.070029. PMID 19737740.
- Song J, da Costa KA, Fischer LM, Kohlmeier M, Kwock L, Wang S, Zeisel SH (Aug 2005). "Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD)". FASEB Journal 19 (10): 1266–71. doi:10.1096/fj.04-3580com. PMC 1256033. PMID 16051693.
- Ivanov A, Nash-Barboza S, Hinkis S, Caudill MA (Feb 2009). "Genetic variants in phosphatidylethanolamine N-methyltransferase and methylenetetrahydrofolate dehydrogenase influence biomarkers of choline metabolism when folate intake is restricted". Journal of the American Dietetic Association 109 (2): 313–8. doi:10.1016/j.jada.2008.10.046. PMC 2655101. PMID 19167960.
- da Costa KA, Kozyreva OG, Song J, Galanko JA, Fischer LM, Zeisel SH (Jul 2006). "Common genetic polymorphisms affect the human requirement for the nutrient choline". FASEB Journal 20 (9): 1336–44. doi:10.1096/fj.06-5734com. PMC 1574369. PMID 16816108.
- Saito A, Kawamoto M, Kamatani N (Jun 2009). "Association study between single-nucleotide polymorphisms in 199 drug-related genes and commonly measured quantitative traits of 752 healthy Japanese subjects". Journal of Human Genetics 54 (6): 317–23. doi:10.1038/jhg.2009.31. PMID 19343046.
- Vance DE, Walkey CJ, Cui Z (Sep 1997). "Phosphatidylethanolamine N-methyltransferase from liver". Biochimica et Biophysica Acta 1348 (1-2): 142–50. doi:10.1016/s0005-2760(97)00108-2. PMID 9370326.
- Dong H, Wang J, Li C, Hirose A, Nozaki Y, Takahashi M, Ono M, Akisawa N, Iwasaki S, Saibara T, Onishi S (May 2007). "The phosphatidylethanolamine N-methyltransferase gene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population". Journal of Hepatology 46 (5): 915–20. doi:10.1016/j.jhep.2006.12.012. PMID 17391797.
- Resseguie M, Song J, Niculescu MD, da Costa KA, Randall TA, Zeisel SH (Aug 2007). "Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes". FASEB Journal 21 (10): 2622–32. doi:10.1096/fj.07-8227com. PMC 2430895. PMID 17456783.
- Li H, Zhang H, Liu L, Ju G, Jin S, Ye L, Zhang X, Wei J (Sep 2009). "No association of the rs4646396 SNP in the PEMT locus with schizophrenia in a Chinese case-control sample". Psychiatry Research 169 (2): 176–7. doi:10.1016/j.psychres.2008.11.004. PMID 19647326.
- Caudill MA, Dellschaft N, Solis C, Hinkis S, Ivanov AA, Nash-Barboza S, Randall KE, Jackson B, Solomita GN, Vermeylen F (Apr 2009). "Choline intake, plasma riboflavin, and the phosphatidylethanolamine N-methyltransferase G5465A genotype predict plasma homocysteine in folate-deplete Mexican-American men with the methylenetetrahydrofolate reductase 677TT genotype". The Journal of Nutrition 139 (4): 727–33. doi:10.3945/jn.108.100222. PMC 2714377. PMID 19211833.
- Shields DJ, Lingrell S, Agellon LB, Brosnan JT, Vance DE (Jul 2005). "Localization-independent regulation of homocysteine secretion by phosphatidylethanolamine N-methyltransferase". The Journal of Biological Chemistry 280 (29): 27339–44. doi:10.1074/jbc.M504658200. PMID 15927961.
- Liu Y, Zhang H, Ju G, Zhang X, Xu Q, Liu S, Yu Y, Shi J, Boyle S, Wang Z, Shen Y, Wei J (Sep 2007). "A study of the PEMT gene in schizophrenia". Neuroscience Letters 424 (3): 203–6. doi:10.1016/j.neulet.2007.07.038. PMID 17720317.
- Shields DJ, Altarejos JY, Wang X, Agellon LB, Vance DE (Sep 2003). "Molecular dissection of the S-adenosylmethionine-binding site of phosphatidylethanolamine N-methyltransferase". The Journal of Biological Chemistry 278 (37): 35826–36. doi:10.1074/jbc.M306308200. PMID 12842883.
- Xu X, Gammon MD, Zeisel SH, Lee YL, Wetmur JG, Teitelbaum SL, Bradshaw PT, Neugut AI, Santella RM, Chen J (Jun 2008). "Choline metabolism and risk of breast cancer in a population-based study". FASEB Journal 22 (6): 2045–52. doi:10.1096/fj.07-101279. PMC 2430758. PMID 18230680.
- Tessitore L, Marengo B, Vance DE, Papotti M, Mussa A, Daidone MG, Costa A (2003). "Expression of phosphatidylethanolamine N-methyltransferase in human hepatocellular carcinomas". Oncology 65 (2): 152–8. doi:10.1159/000072341. PMID 12931022.
- Jun DW, Han JH, Jang EC, Kim SH, Kim SH, Jo YJ, Park YS, Chae JD (Jun 2009). "Polymorphisms of microsomal triglyceride transfer protein gene and phosphatidylethanolamine N-methyltransferase gene in alcoholic and nonalcoholic fatty liver disease in Koreans". European Journal of Gastroenterology & Hepatology 21 (6): 667–72. doi:10.1097/MEG.0b013e3283196adc. PMID 19262398.
- Chen SN, Cilingiroglu M, Todd J, Lombardi R, Willerson JT, Gotto AM, Ballantyne CM, Marian AJ (2009). "Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis". BMC Medical Genetics 10: 111. doi:10.1186/1471-2350-10-111. PMC 2775733. PMID 19878569.
External links
- Phosphatidylethanolamine N-Methyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)
|
Transferase: one carbon transferases (EC 2.1)
|
|
| 2.1.1: Methyl- |
| N- |
- Histamine N-methyltransferase
- Phenylethanolamine N-methyltransferase
- Amine N-methyltransferase
- Phosphatidylethanolamine N-methyltransferase
|
|
| O- |
- 5-hydroxyindole-O-methyltransferase/Acetylserotonin O-methyltransferase
- Catechol-O-methyl transferase
|
|
| Homocysteine |
- Betaine-homocysteine methyltransferase
- Homocysteine methyltransferase
- Methionine synthase
|
|
| Other |
- Phosphatidyl ethanolamine methyltransferase
- DNMT3B
- Histone methyltransferase
- Thymidylate synthase
- DNA methyltransferase
- Thiopurine methyltransferase
|
|
|
2.1.2: Hydroxymethyl-,
Formyl- and Related |
| Hydroxymethyltransferase |
- Serine hydroxymethyltransferase
- 3-methyl-2-oxobutanoate hydroxymethyltransferase
|
|
| Formyltransferase |
- Phosphoribosylglycinamide formyltransferase
- Inosine monophosphate synthase
|
|
| Other |
- Glutamate formimidoyltransferase
- Aminomethyltransferase
|
|
|
2.1.3: Carboxy-
and Carbamoyl |
| Carboxy |
- methylmalonyl-CoA carboxytransferase
|
|
| Carbamoyl |
- Aspartate carbamoyltransferase
- Ornithine carbamoyltransferase
- Oxamate carbamoyltransferase
- Putrescine carbamoyltransferase
- 3-hydroxymethylcephem carbamoyltransferase
- Lysine carbamoyltransferase
- N-acetylornithine carbamoyltransferase
|
|
|
| 2.1.4: Amidine |
- Arginine:glycine amidinotransferase
|
|
|
Enzymes
|
|
| Activity |
- Active site
- Binding site
- Catalytic triad
- Oxyanion hole
- Enzyme promiscuity
- Catalytically perfect enzyme
- Coenzyme
- Cofactor
- Enzyme catalysis
- Enzyme kinetics
- Lineweaver–Burk plot
- Michaelis–Menten kinetics
|
|
| Regulation |
- Allosteric regulation
- Cooperativity
- Enzyme inhibitor
|
|
| Classification |
- EC number
- Enzyme superfamily
- Enzyme family
- List of enzymes
|
|
| Types |
- EC1 Oxidoreductases(list)
- EC2 Transferases(list)
- EC3 Hydrolases(list)
- EC4 Lyases(list)
- EC5 Isomerases(list)
- EC6 Ligases(list)
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.