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Pathway Description
Betaine Metabolism
Homo sapiens
Metabolic Pathway
Created: 2013-08-01
Last Updated: 2023-10-29
Betaine (or trimethylglycine) is similar to choline (trimethylaminoethanol) but differs in choline's terminal carboxylic acid group trimethylglycine is reduced to a hydroxyl group. Betaine is obtained from diet as betaine or compounds containing choline in foods such as whole grains, beets and spinach. Betaine can also be synthesized from choline in the liver and kidney. First, choline is oxidized to betaine aldehyde by mitochondrial choline oxidase (choline dehydrogenase). Then, betaine aldehyde dehydrogenase oxidizes betaine aldehyde to betaine in the mitochondria or cytoplasm. In the liver, betaine functions as a methyl donor similar to choline, folic acid, S-adenosyl methionine and vitamin B12. Methyl donors are important for liver function, cellular replication and detoxification reactions. Betaine is also involved in the production of carnitine to protect from kidney damage and functions as an osmoprotectant in the inner medulla.
References
Betaine Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Day CR, Kempson SA: Betaine chemistry, roles, and potential use in liver disease. Biochim Biophys Acta. 2016 Jun;1860(6):1098-106. doi: 10.1016/j.bbagen.2016.02.001. Epub 2016 Feb 2.
Pubmed: 26850693
Brocker C, Lassen N, Estey T, Pappa A, Cantore M, Orlova VV, Chavakis T, Kavanagh KL, Oppermann U, Vasiliou V: Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress. J Biol Chem. 2010 Jun 11;285(24):18452-63. doi: 10.1074/jbc.M109.077925. Epub 2010 Mar 5.
Pubmed: 20207735
Plecko B, Paul K, Paschke E, Stoeckler-Ipsiroglu S, Struys E, Jakobs C, Hartmann H, Luecke T, di Capua M, Korenke C, Hikel C, Reutershahn E, Freilinger M, Baumeister F, Bosch F, Erwa W: Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene. Hum Mutat. 2007 Jan;28(1):19-26. doi: 10.1002/humu.20433.
Pubmed: 17068770
Lee P, Kuhl W, Gelbart T, Kamimura T, West C, Beutler E: Homology between a human protein and a protein of the green garden pea. Genomics. 1994 May 15;21(2):371-8. doi: 10.1006/geno.1994.1279.
Pubmed: 8088832
Weisberg IS, Park E, Ballman KV, Berger P, Nunn M, Suh DS, Breksa AP 3rd, Garrow TA, Rozen R: Investigations of a common genetic variant in betaine-homocysteine methyltransferase (BHMT) in coronary artery disease. Atherosclerosis. 2003 Apr;167(2):205-14. doi: 10.1016/s0021-9150(03)00010-8.
Pubmed: 12818402
Garrow TA: Purification, kinetic properties, and cDNA cloning of mammalian betaine-homocysteine methyltransferase. J Biol Chem. 1996 Sep 13;271(37):22831-8. doi: 10.1074/jbc.271.37.22831.
Pubmed: 8798461
Park EI, Garrow TA: Interaction between dietary methionine and methyl donor intake on rat liver betaine-homocysteine methyltransferase gene expression and organization of the human gene. J Biol Chem. 1999 Mar 19;274(12):7816-24. doi: 10.1074/jbc.274.12.7816.
Pubmed: 10075673
Leclerc D, Campeau E, Goyette P, Adjalla CE, Christensen B, Ross M, Eydoux P, Rosenblatt DS, Rozen R, Gravel RA: Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders. Hum Mol Genet. 1996 Dec;5(12):1867-74. doi: 10.1093/hmg/5.12.1867.
Pubmed: 8968737
Li YN, Gulati S, Baker PJ, Brody LC, Banerjee R, Kruger WD: Cloning, mapping and RNA analysis of the human methionine synthase gene. Hum Mol Genet. 1996 Dec;5(12):1851-8. doi: 10.1093/hmg/5.12.1851.
Pubmed: 8968735
Chen LH, Liu ML, Hwang HY, Chen LS, Korenberg J, Shane B: Human methionine synthase. cDNA cloning, gene localization, and expression. J Biol Chem. 1997 Feb 7;272(6):3628-34.
Pubmed: 9013615
Vugrek O, Beluzic R, Nakic N, Mudd SH: S-adenosylhomocysteine hydrolase (AHCY) deficiency: two novel mutations with lethal outcome. Hum Mutat. 2009 Apr;30(4):E555-65. doi: 10.1002/humu.20985.
Pubmed: 19177456
Coulter-Karis DE, Hershfield MS: Sequence of full length cDNA for human S-adenosylhomocysteine hydrolase. Ann Hum Genet. 1989 May;53(2):169-75.
Pubmed: 2596825
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Chen R, Chen Z, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang J, Wang J, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA: The DNA sequence, annotation and analysis of human chromosome 3. Nature. 2006 Apr 27;440(7088):1194-8. doi: 10.1038/nature04728.
Pubmed: 16641997
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22.
Pubmed: 24275569
Shields DJ, Agellon LB, Vance DE: Structure, expression profile and alternative processing of the human phosphatidylethanolamine N-methyltransferase (PEMT) gene. Biochim Biophys Acta. 2001 May 31;1532(1-2):105-14. doi: 10.1016/s1388-1981(01)00122-6.
Pubmed: 11420179
Resseguie M, Song J, Niculescu MD, da Costa KA, Randall TA, Zeisel SH: Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes. FASEB J. 2007 Aug;21(10):2622-32. doi: 10.1096/fj.07-8227com. Epub 2007 Apr 24.
Pubmed: 17456783
Walkey CJ, Shields DJ, Vance DE: Identification of three novel cDNAs for human phosphatidylethanolamine N-methyltransferase and localization of the human gene on chromosome 17p11.2. Biochim Biophys Acta. 1999 Jan 4;1436(3):405-12. doi: 10.1016/s0005-2760(98)00147-7.
Pubmed: 9989271
Horikawa S, Tsukada K: Molecular cloning and developmental expression of a human kidney S-adenosylmethionine synthetase. FEBS Lett. 1992 Nov 2;312(1):37-41. doi: 10.1016/0014-5793(92)81405-b.
Pubmed: 1426236
Panayiotidis MI, Stabler SP, Ahmad A, Pappa A, Legros LH Jr, Hernandez-Saavedra D, Schneider BK, Allen RH, Vasiliou V, McCord JM, Kotb M, White CW: Activation of a novel isoform of methionine adenosyl transferase 2A and increased S-adenosylmethionine turnover in lung epithelial cells exposed to hyperoxia. Free Radic Biol Med. 2006 Jan 15;40(2):348-58. doi: 10.1016/j.freeradbiomed.2005.09.004. Epub 2005 Nov 18.
Pubmed: 16413417
LeGros L, Halim AB, Chamberlin ME, Geller A, Kotb M: Regulation of the human MAT2B gene encoding the regulatory beta subunit of methionine adenosyltransferase, MAT II. J Biol Chem. 2001 Jul 6;276(27):24918-24. doi: 10.1074/jbc.M102816200. Epub 2001 May 3.
Pubmed: 11337507
LeGros HL Jr, Halim AB, Geller AM, Kotb M: Cloning, expression, and functional characterization of the beta regulatory subunit of human methionine adenosyltransferase (MAT II). J Biol Chem. 2000 Jan 28;275(4):2359-66. doi: 10.1074/jbc.275.4.2359.
Pubmed: 10644686
Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Bocher M, Blocker H, Bauersachs S, Blum H, Lauber J, Dusterhoft A, Beyer A, Kohrer K, Strack N, Mewes HW, Ottenwalder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A: Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome Res. 2001 Mar;11(3):422-35. doi: 10.1101/gr.gr1547r.
Pubmed: 11230166
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