• 1
    Garrow TA. Purification, kinetic properties, and cDNA cloning of mammalian betaine-homocysteine methyltransferase. J Biol Chem 1996; 271: 2283122838.
  • 2
    Millian NS, Garrow TA. Human betaine-homocysteine methyltransferase is a zinc metalloenzyme. Arch Biochem Biophys 1998; 356: 9398.
  • 3
    Neece DJ, Griffiths MA, Garrow TA. Isolation and characterization of a mouse betaine-homocysteine S-methyltransferase gene and pseudogene. Gene 2000; 250: 3140.
  • 4
    Finkelstein JD. Methionine metabolism in liver diseases. Am J Clin Nutr 2003; 77: 10941095.
  • 5
    Finkelstein JD. Inborn errors of sulfur-containing amino acid metabolism. J Nutr 2006; 136(suppl 6): S1750S1754.
  • 6
    Emmert JL, Webel DM, Biehl RR, Griffiths MA, Garrow LS, Garrow TA, et al. Hepatic and renal betaine-homocysteine methyltransferase activity in pigs as affected by dietary intakes of sulfur amino acids, choline, and betaine. J Anim Sci 1998; 76: 606610.
  • 7
    Finkelstein JD, Martin JJ. Methionine metabolism in mammals. Distribution of homocysteine between competing pathways. J Biol Chem 1984; 259: 95089513.
  • 8
    Selhub J, Miller JW. The pathogenesis of homocysteinemia: interruption of the coordinate regulation by sadenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr 1992; 55: 131138.
  • 9
    Reed MC, Nijhout HF, Sparks R, Ulrich CM. A mathematical model of the methionine cycle. J Theor Biol 2004; 226: 3343.
  • 10
    Weisberg IS, Park E, Ballman KV, Berger P, Nunn M, Suh DS, et al. Investigations of a common genetic methyltransferase (BHMT) variant in betaine-homocysteine in coronary artery disease. Atherosclerosis 2003; 167: 205214.
  • 11
    Heil SG, Lievers KJ, Boers GH, Verhoef P, den Heijer M, Trijbels FJ, et al. Betaine-homocysteine methyltransferase (BHMT): genomic sequencing and relevance to hyperhomocysteinemia and vascular disease in humans. Mol Genet Metab 2000; 71: 511519.
  • 12
    Zhu HP, Curry S, Wen S, Wicker NJ, Shaw GM, Lammer EJ, et al. Are the betaine-homocysteine methyltransferase (BHMT and BHMT2) genes risk factors for spina bifida and orofacial clefts? Am J Med Genet A 2005; 135: 274277.
  • 13
    Boyles AL, Billups AV, Deak KL, Siegel DG, Mehltretter L, Slifer SH, et al. Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions. Environ Health Perspect 2006; 114: 15471552.
  • 14
    Watanabe M, Osada J, Aratani Y, Kluckman K, Reddick R, Malinow MR, et al. Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia. Proc Natl Acad Sci U S A 1995; 92: 15851589.
  • 15
    Barak AJ, Beckenhauer HC, Junnila M, Tuma DJ. Dietary betaine promotes generation of hepatic S-adenosylmethionine and protects the liver from ethanol-induced fatty infiltration. Alcohol Clin Exp Res 1993; 17: 552555.
  • 16
    Werstuck GH, Lentz SR, Dayal S, Hossain GS, Sood SK, Shi YY, et al. Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways. J Clin Invest 2001; 107: 12631273.
  • 17
    Esfandiari F, Villanueva JA, Wong DH, French SW, Halsted CH. Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am J Physiol Gastrointest Liver Physiol 2005; 289: G54G63.
  • 18
    Ji C, Kaplowitz N. Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice. Gastroenterology 2003; 124: 14881499.
  • 19
    Ji C, Deng Q, Kaplowitz N. Role of TNF-alpha in ethanol-induced hyperhomocysteinemia and murine alcoholic liver injury. HEPATOLOGY 2004; 40: 442451.
  • 20
    Ji C, Chan C, Kaplowitz N. Predominant role of sterol response element binding proteins (SREBP) lipogenic pathways in hepatic steatosis in the murine intragastric ethanol feeding model. J Hepatol 2006; 45: 717724.
  • 21
    Sowden MP, Collins HL, Smith HC, Garrow TA, Sparks JD, Sparks CE. Apolipoprotein B mRNA and lipoprotein secretion are increased in McArdle RH-7777 cells by expression of betaine-homocysteine S-methyltransferase. Biochem J 1999; 341(pt 3): 639645.
  • 22
    Collins HL, Sparks CE, Sparks JD. B48 is preferentially translated over B100 in cells with increased endogenous apo B mRNA. Biochem Biophys Res Commun 2000; 273: 11561160.
  • 23
    Sparks JD, Collins HL, Chirieac DV, Cianci J, Jokinen J, Sowden MP, et al. Hepatic very-low-density lipoprotein and apolipoprotein B production are increased following in vivo induction of betaine-homocysteine S-methyltransferase. Biochem J 2006; 395: 363371.
  • 24
    Matsumaru K, Ji C, Kaplowitz N. Mechanisms for sensitization to TNF-induced apoptosis by acute glutathione depletion in murine hepatocytes. HEPATOLOGY 2003; 37: 14251434.
  • 25
    Mudd SH, Brosnan JT, Brosnan ME, Jacobs RL, Stabler SP, Allen RH, et al. Methyl balance and transmethylation fluxes in humans. Am J Clin Nutr 2007; 85: 1925.
  • 26
    Avila MA, Berasain C, Torres L, Martin-Duce A, Corrales FJ, Yang H, et al. Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma. J Hepatol 2000; 33: 907914.
  • 27
    Ji C, Kaplowitz N. ER stress: Can the liver cope? J Hepatol 2006; 45: 321333.
  • 28
    Jakubowski H. Pathophysiological consequences of homocysteine excess. J Nutr 2006; 136(6 suppl): 1741S1749S.
  • 29
    Pajares MA, Perez-Sala D. Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism? Cell Mol Life Sci 2006; 63: 27922803.
  • 30
    Zhang J, Herscovitz H. Nascent lipidated apolipoprotein B is transported to the Golgi as an incompletely folded intermediate as probed by its association with network of endoplasmic reticulum molecular chaperones, GRP94, ERp72, BiP, calreticulin, and cyclophilin B. J Biol Chem 2003; 278: 74597468.
  • 31
    Graf D, Kurz AK, Reinehr R, Fischer R, Kircheis G, Haussinger D. Prevention of bile acid-induced apoptosis by betaine in rat liver. HEPATOLOGY 2002; 36(4 pt 1): 829839.
  • 32
    Kharbanda KK, Mailliard ME, Baldwin CR, Beckenhauer HC, Sorrell MF, Tuma DJ. Betaine attenuates alcoholic steatosis by restoring phosphatidylcholine generation via the phosphatidylethanolamine methyltransferase pathway. J Hepatol 2007; 46: 314321.
  • 33
    Li Z, Agellon LB, Allen TM, Umeda M, Jewell L, Mason A, et al. The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. Cell Metab 2006; 3: 321331.
  • 34
    Ou X, Yang H, Ramani K, Ara AI, Chen H, Mato JM, et al. Inhibition of human betaine-homocysteine methyltransferase expression by S-adenosylmethionine and methylthioadenosine. Biochem J 2007; 401: 8796.