Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
 2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcoholic liver disease is associated with abnormal hepatic methionine metabolism, including increased levels of homocysteine and S-adenosylhomocysteine (SAH) and reduced levels of S-adenosylmethionine (SAM) and glutathione (GSH). The concept that abnormal methionine metabolism is involved in the pathogenesis of alcoholic liver disease was strengthened by our previous findings in a micropig model where combining dietary folate deficiency with chronic ethanol feeding produced maximal changes in these metabolites together with early onset of microscopic steatohepatitis and an eightfold increase in plasma aspartate aminotransferase. The goal of the present study was to determine potential mechanisms for abnormal levels of these methionine metabolites by analyzing the transcripts and activities of transmethylation enzymes in the livers of the same micropigs. Ethanol feeding or folate deficiency, separately or in combination, decreased transcript levels of methylenetetrahydrofolate reductase (MTHFR), methionine adenosyltransferase (MAT1A), glycine-N-methyltransferase (GNMT) and S-adenosylhomocysteine hydrolase (SAHH). Ethanol feeding alone reduced the activities of methionine synthase (MS) and MATIII and increased the activity of GNMT. Each diet, separately or in combination, decreased the activities of MTHFR and SAHH. In conclusion, the observed abnormal levels of methionine metabolites in this animal model of accelerated alcoholic liver injury can be ascribed to specific effects of ethanol with or without folate deficiency on the expressions and activities of hepatic enzymes that regulate transmethylation reactions. These novel effects on transmethylation reactions may be implicated in the pathogenesis of alcoholic liver disease.
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PMID:Hepatic transmethylation reactions in micropigs with alcoholic liver disease. 1512 59

No direct data exist on the influence of supranormal intakes of sulfur amino acids on immune function in humans. However 3 major products of sulfur amino acids, glutathione (GSH), homocysteine (Hcy), and taurine (Tau), influence, mainly, inflammatory aspects of the immune response in vitro and in vivo. Methionine intakes above approximately 1 g/d transiently raise plasma Tau, Hcy, and GSH. Tau and GSH ameliorate inflammation. Hcy has the opposite effect. A biphasic relation, between cellular GSH and CD4+ and CD8+ numbers occurs in healthy men. How changes in sulfur amino acid intake influence this phenomenon is unknown. In animals, high Tau intakes are antiinflammatory. How immune function in humans is affected is unknown. A positive relation between plasma neopterin (a marker of a Th-1-type immune response) and Hcy indicates that Hcy may play a part in inflammatory aspects of Parkinson's disease and aging. In vitro, Hcy, at concentrations seen following consumption of approximately 6 g L-methionine/d in adults, increases the interactions among T lymphocytes, monocytes, and endothelium. Whether a similar phenomenon occurs in vivo is unknown. Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with raised plasma Hcy in young but not old subjects. The relation of this observation to immune function is unknown. The relationships among Hcy, inflammatory aspects of disease, and in vitro alterations in immune cell behavior create a cautionary note about supplementation of diets with l-methionine to raise intake above approximately 1 g/d. Studies directly linking methionine intake, genetics, plasma Hcy, Tau, and GSH and immune function are needed.
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PMID:The effects of sulfur amino acid intake on immune function in humans. 1670 36