The biochemical and toxicological significance of hypermethionemia: New insights and clinical relevance

Expert Opinion on Drug Metabolism and Toxicology

Volumn 6, Issue 11, 2010, Pages 1333-1346

  Dever, Joseph T ^a   Elfarra, Adnan A ^b  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

^b UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

hepatocytes; hypermethionemia; methionine; sulfoxidation; transamination; transmethylation

Indexed keywords

ADENOSYLHOMOCYSTEINASE; AMINOOXYACETIC ACID; CYSTATHIONINE BETA SYNTHASE; GLYCINE METHYLTRANSFERASE; METHIONINE; METHIONINE ADENOSYLTRANSFERASE; METHIONINE ADENOSYLTRANSFERASE I; METHIONINE ADENOSYLTRANSFERASE III; S ADENOSYLMETHIONINE; UNCLASSIFIED DRUG;

ADENOSYLHOMOCYSTEINASE DEFICIENCY; AMINO ACID DEFICIENCY; AMINO ACID METABOLISM; BIOACCUMULATION; CARDIOVASCULAR DISEASE; CHEMICAL ANALYSIS; CHOLESTASIS; DETOXIFICATION; ENZYME DEFICIENCY; FATTY LIVER; GLYCINE METHYLTRANSFERASE DEFICIENCY; HOMOCYSTINURIA; HUMAN; HYPERMETHIONEMIA; LIVER CELL; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER FAILURE; LIVER FIBROSIS; LIVER INJURY; LIVER PROTECTION; LIVER TOXICITY; METHIONINE ADENOSYLTRANSFERASE DEFICIENCY; METHYLATION; NEUROLOGIC DISEASE; NONHUMAN; REVIEW; SEX DIFFERENCE; SULFOXIDATION; TOTAL PARENTERAL NUTRITION; TRANSAMINATION;

ANIMALS; BIOLOGICAL MARKERS; FEMALE; HEPATOCYTES; HUMANS; LIVER; LIVER DISEASES; MALE; METHIONINE; METHYLATION; MICE; SEX FACTORS; SULFOXIDES; TRANSAMINASES;

RODENTIA;

EID: 77958506553     PISSN: 17425255     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425255.2010.522177     Document Type: Review

References (86)

1. Finkelstein JD. Methionine metabolism in mammals. J Nutr Biochem 1990;1:228-237
2. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet 2002;3:415-426
3. Garcia-Trevijano ER, Latasa MU, Carretero MV, et al. S-Adenosylmethionine regulates MAT1A and MAT2A gene expression in cultured rat hepatocytes: a new role for S-adenosylmethionine in the maintenance of the differentiated status of the liver. FASEB J 2000;14:2511-2518
4. Finkelstein JD. Metabolic regulatory properties of S-Adenosylmethionine and S-adenosylhomocysteine. Clin Chem Lab Med 2007;45:1694-1699
5. Lu SC, Alvarez L, Huang ZZ, et al. Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation. Proc Natl Acad Sci USA 2001;98:5560-5565
6. Mato JM, Martinez-Chantar ML, Lu SC. Methionine metabolism and liver disease. Annu Rev Nutr 2008;28:273-293
7. Hardwick DF, Applegarth DA, Cockcroft DM, et al. Pathogenesis of methionine-induced toxicity. Metabolism 1970;19:381-391
8. Shinozuka H, Estes LW, Farber E. Studies on acute methionine toxicity. I. Nucleolar disaggregation in guinea pig hepatic cells with methionine or ethionine and its reversal with adenine. Am J Pathol 1971;64:241-249
9. Cox R, Martin JT, Shinozuka H. Studies on acute methionine toxicity. II. Inhibition of ribonucleic acid synthesis in guinea pig liver by methionine and ethionine. Lab Invest 1973;29:54-59
10. Finkelstein A, Benevenga NJ. The effect of methanethiol and methionine toxicity on the activities of cytochrome c oxidase and enzymes involved in protection from peroxidative damage. J Nutr 1986;116:204-215
11. Dever JT, Elfarra AA. L-methionine toxicity in freshly isolated mouse hepatocytes is gender-dependent and mediated in part by transamination. J Pharmacol Exp Ther 2008;326:809-817
12. Dever JT, Elfarra AA. L-Methionine-dl-sulfoxide metabolism and toxicity in freshly isolated mouse hepatocytes: Gender differences and inhibition with aminooxyacetic acid. Drug Metab Dispos 2008;36:2252-2260
13. Dever JT, Elfarra AA. Gender differences in methionine accumulation and metabolism in freshly isolated mouse hepatocytes: potential roles in toxicity. Toxicol Appl Pharmacol 2009;236:358-365
14. Hesse H, Kreft O, Maimann S, et al. Current understanding of the regulation of methionine biosynthesis in plants. J Exp Bot 2004;55:1799-1808
15. Oz HS, Chen TS, Neuman M. Methionine deficiency and hepatic injury in a dietary steatohepatitis model. Dig Dis Sci 2008;53:767-776
16. Newberne PM, Young VR. Effect of diets marginal in methionine and choline with and without vitamin B12 on rat liver and kidney. J Nutr 1966;89:69-79
17. Grandison RC, Piper MDW, Partridge L. Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 2009;462:1061-1065
18. Benevenga NJ. Toxicities of methionine and other amino acids. J Agr Food Chem 1974;22:2-9
19. Steele RD, Barber TA, Lalich J, et al. Effects of dietary 3-methylthiopropionate on metabolism, growth, and hematopoiesis in the rat. J Nutr 1979;109:1739-1751
20. Toborek M, Kopieczna-Grzebieniak E, Drozdz M, et al. Increased lipid peroxidation and antioxidant activity in methionine-induced hepatitis in rabbits. Nutrition 1996;12:534-537
21. Mori N, Hirayama K. Long-term consumption of methionine-supplemented diet increases iron and lipid peroxide levels in rat liver. J Nutr 2000;130:2349-2355
22. Martinez-chantar ML, Corrales FJ, Martinez-Cruz LA, et al. Spontaneous oxidative stress and liver tumors in mice lacking methionine adenosyltransferase 1A. FASEB J 2002;16:1292-1294
23. Orentriech N, Matias JR, DeFelice A, et al. Low methionine ingestion by rats extends life span. J Nutr 1993;123:269-274
24. Miller RA, Buehner G, Chang Y, et al. Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-1 and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging cell 2005;4:119-125
25. Sun L, Sadighi Akha AA, Miller RA, et al. Life-span extension in mice by preweaning food restriction and by methionine restriction in middle age. J Gerontol A Biol Sci Med Sci 2009;64A:711-722
26. Dever JT, Elfarra AA. In vivo metabolism of L-methionine in mice: evidence for stereoselective formation of methionine-d-sulfoxide and quantitation of other major metabolites. Drug Metab Dispos 2006;34:2036-2043
27. Garlick PJ. Toxicity of methionine in humans. J Nutr 2006;136:1722S-1725S
28. Mudd SH, Levy HL, Tangerman A, et al. Isolated persistent hypermethionemia. Am J Hum Genet 1995;57:882-892
29. Baric I. Inherited disorders in the conversion of methionine to homocysteine. J Inherit Metab Dis 2009;32:459-471
30. Couce ML, Boveda MD, Castineiras DE, et al. Hypermethionemia due to methionine adenosyltransferase I/III (MAT I/III) deficiency. Diagnosis in an expanded neonatal screening programme. J Inherit Metab Dis 2008;31:467-468
31. Gahl WA, Bernardini I, Finkelstein JD, et al. Transsulfuration in an adult with hepatic methionine adenosyltransferase deficiency. J Clin Invest 1988;81:390-397
32. Blom HJ, Boers GHJ, van den Elzen JPAM, et al. Transamination of methionine in humans. Clin Sci (Colch) 1989;76:43-49
33. Chamberlin ME, Ubagai T, Mudd SH, et al. Demyelination of the brain is associated with methionine adenosyltransferase I/III deficiency. J Clin Invest 1996;98:1021-1027
34. Mudd SH, Cerone R, Schiaffino MC, et al. Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethionaemia. J Inherit Metab Dis 2001;24:448-464
35. Augoustides-Savvopoulou P, Luka Z, Karyda S, et al. Glycine N-methyltransferase deficiency: a new patient with a novel mutation. J Inherit Metab Dis 2003;26:745-759
36. Luka Z, Capdevila A, Mato JM, et al. A glycine N-methyltransferase knockout mouse model for humans with deficiency of this enzyme. Transgenic Res 2006;15:393-397
37. Liu SP, Li YS, Chen YJ, et al. Glycine N-methyltransferase -/-mice develop chronic hepatitis and glycogen storage disease in the liver. Hepatology 2007;46:1413-1425
38. Martinez-Chantar ML, Vazquez-Chantada M, Ariz U, et al. Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice. Hepatology 2008;47:1191-1199
39. Baric I, Fumic K, Glenn B, et al. S-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism. Proc Natl Acad Sci USA 2004;101:4234-4239
40. Baric I, Cuk M, Fumic K, et al. S-Adenosylhomocysteine hydrolase deficiency: a second patient, the younger brother of the index patient, and outcomes during therapy. J Inhert Metab Dis 2005;28:885-902
41. Buist NRM, Glenn B, Vugrek O, et al. S-Adenosylhomocysteine hydrolase deficiency in a 26-year-old man. J Inherit Metab Dis 2006;29:538-545
42. Tangerman A, Wilcken B, Levy HL, et al. Methionine transamination in patients with homocystinuria due to cystathionine beta-synthase deficiency. Metabolism 2000;49:1071-1077
43. Blom HJ, Boers G, Tribels J, et al. Cystathionine-synthase-deficient patients do not use the transamination pathway of methionine to reduce hypermethionemia and homocystineria. Metabolism 1989;38:577-582
44. Naughten E, Yap S, Mayne PD. Newborn screening for homocystinuria: Irish and world experience. Eur J Pediatr 1998;157(Suppl 2):S84-7
45. Clarke R. Homocysteine studies collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 2002;288:2015-2022
46. Anderson JL, Muhlestein JB, Horne BD, et al. Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease. Circulation 2000;102:1227-1232
47. Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 2002;346:476-483
48. Jakubowski H. Molecular basis of homocysteine toxicity in humans. Cell Mol Life Sci 2004;61:470-487
49. Brown MR, Putnam TC. Cholestasis associated with central intravenous nutrition in infants. NY State J Med 1978;78:27-30
50. Coran AG, Drongowski RA. Studies on the toxicity and efficacy of a new amino acid solution in pediatric parenteral nutrition. J Parenter Enteral Nutr 1987;11:368
51. Moss RL, das JB, Ansari G, et al. Hepatobiliary dysfunction during total parenteral nutrition is caused by the infusate, not the route of administration. J Pediatr Surg 1993;28:391-397
52. Ekema G, Falchetti D, Boroni G, et al. Reversal of severe parenteral nutrition-associated liver disease in an infant with short bowel syndrome using parenteral fish oil (Omega-3 fatty acids). J Pediatr Surg 2008;43:1191-1195
53. Moss LR, Haynes AL, Pastuszyn A, et al. Methionine infusion reproduces liver injury of parenteral nutrition cholestasis. Pediatr Res 1999;45:664-668
54. Riedijk MA, Stoll B, Chacko S, et al. Methionine transmethylation and transsulfuration in the piglet gastrointestinal tract. Proc Natl Acad Sci USA 2007;104:3408-3413
55. Shoveller AK, Brunton JA, Pencharz PB, et al. The methionine requirement is lower in neonatal piglets fed parenterally than in those fed enterally. J Nutr 2003;133:1390-1397
56. Higashi T. Impaired metabolism of methionine in severe liver diseases I. Clinical and pathophysiological significance of elevated serum methionine levels. Gastroenterol Jpn 1982;17:117-124
57. Tietge UJF, Bahr MJ, Manns MP, et al. Hepatic amino-acid metabolism in liver cirrhosis and in the long-term course after liver transplantation. Transplant Int 2003;18:1-8
58. Marchesini G, Bugianesi E, Bianchi G, et al. Defective methionine metabolism in cirrhosis: relation to severity of liver disease. Hepatology 1992;16:149-155
59. Avila MA, Berasain C, Torres L, et al. Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma. J Hepatol 2000;33:907-914
60. Finkelstein JD. Methionine metabolism in liver diseases. Am J Clin Nutr 2003;77:1094-1095
61. Lu SC. S-Adenosylmethionine. Int J Biochem Cell B 2000;32:391-395
62. Regina M, Korhonen V, Smith T, et al. Methionine toxicity in the rat in relation to hepatic accumulation of S-adenosylmethionine: prevention by dietary stimulation of the hepatic transsulfuration pathway. Arch Biochem Biophys 1993;300:598-607
63. Duerre JA. Effect of 3-deazaadenosine on methionine metabolism in isolated perfused livers. Biochem Cell Biol 1988;66:1032-1039
64. Mato JM, Lu SC. Role of S-Adenosyl-L-methionine in liver health and injury. Hepatology 2007;45:1306-1312
65. Lu SC, Ramani K, Ou X, et al. S-Adenosylmethionine in the chemoprevention and treatment of hepatocellular carcinoma in a rat model. Hepatology 2009;50:462-471
66. Wang S, Chen H, Sheen L, et al. Methionine and cysteine affect glutathione level, glutathione-related enzyme activities and the expression of glutathione S-transferase isozymes in rat hepatocytes. J Nutr 1997;127:2135-2141
67. Scislowski PWD, Pickard K. Methionine transamination -metabolic function and subcellular compartmentation. Mol Cell Biochem 1993;129:39-45
68. Cooper AJL, Meister A. Isolation and properties of a new glutamine transaminase from rat kidney. J Biol Chem 1974;249:2554-2561
69. Steele RD, Benevenga NJ. Identification of 3-methylthiopropionic acid as an intermediate in mammalian methionine metabolism in vitro. J Biol Chem 1978;253:7844-7850
70. Dixon JL, Benevenga NJ. The decarboxylation of alpha-keto-gamma- methiolbutryate in rat liver mitochondria. Biochem Biophys Res Commun 1980;97:939-946
71. Jones SMA, Yeaman SJ. Oxidative decarboxylation of 4-methylthio-2- oxobutyrate by branched-chain 2-oxo acid dehydrogenase complex. Biochem J 1986;237:621-623
72. Steele RD, Benevenga NJ. The metabolism of 3-methylthiopropionate in rat liver homogenates. J Biol Chem 1979;254:8885-8890
73. Blom HJ, van den Elzen JP, Yap SH, et al. Methanethiol and dimethylsulfide formation from 3-methylthiopropionate in human and rat hepatocytes. Biochim Biophys Acta 1988;972:131-136
74. Konno R, Sasaki M, Asakura S, et al. D-amino-acd oxidase is not present in the mouse liver. Biochem Biophys Acta 1997;1335:173-181
75. Mitchell AD, Benevenga NJ. The role of transamination in methionine oxidation in the rat. J Nutr 1978;108:67-78
76. Bugianesi E, Tangerman A, Ronchi M, et al. Transamination of methionine after loading in patients with cirrhosis. J Hepatol 1996;24:95-100
77. Mashima R, Nakanishi-Ueda T, Yamamoto Y. Simultaneous determination of methionine sulphoxide and methionine in blood plasma using gas chromatography-mass spectrometry. Anal Biochem 2003;313:28-33
78. Duescher RJ, Lawton MP, Philpot RM, et al. Flavin-containing monooxygenase (FMO)-dependent metabolism of methionine and evidence for FMO3 being the major FMO involved in methionine sulfoxidation in rabbit liver and kidney microsomes. J Biol Chem 1994;269:17525-17530
79. Krause RJ, Ripp SL, Sausen PJ, et al. Characterization of the methionine-S-oxidase activity of rat liver and kidney microsomes: immunochemical and kinetic evidence for FMO3 being the major catalyst. Arch Biochem Biophy 1996;333:109-116
80. Ripp SL, Kiyoshi I, Philpot RM, et al. Species and sex differences in expression of flavin-containing monooxygenase form 3 in liver and kidney microsomes. Drug Metab Dispos 1999;27:46-52
81. Ripp SL, Itagaki K, et al. Methionine S-oxidation in human and rabbit liver microsomes: evidence for a high-affinity methionine S-oxidase activity that is distinct from flavin-containing monooxygenase 3. Arch Biochem Biophys 1999;367:322-332
82. Perry TL, Hansen S, MacDougall L. Sulfur-containing amino acids in plasma and urine of homocystinurics. Clin Chim Acta 1965;15:409-420
83. Bauchart-Thevret C, Stoll B, Chacko S, et al. Sulfur amino acid deficiency upregulates intestinal methionine cycle activity and suppresses epithelial growth in neonatal pigs. Am J Physiol Endocrinol Metab 2009;296:E1239-50
84. Storch KJ, Wagner DA, Burke JF, et al. Quantitative study in vivo of methionine cycle in humans using [methyl-2H3]-and [1-13C]methionine. Am J Physiol Endocrinol Metab 1988;255:E322-31
85. Mercier S, Breuille D, Buffiere C, et al. Methionine kinetics are altered in the elderly both in the basal state and after vaccination. Am J Clin Nutr 2006;83:291-298
86. Toue S, Kodama R, Amao M, et al. Screening of toxicity biomarkers for methionine excess in rats. J Nutr 2006;136:1716S-1721S