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The biochemical and toxicological significance of hypermethionemia: new insights and clinical relevance.

ABSTRACT: Disrupted l-methionine (Met) metabolism can lead to hepatic, neurological and cardiovascular dysfunction in humans. Aberrant methyl group flux likely contributes to the development of these pathologies, but when patients also become hypermethionemic, additional toxicological mechanisms may be relevant.Following a discussion of the causes of hypermethionemia in humans, evidence for the toxicological roles and clinical significance of the Met transmethylation (TM), transamination (TA) and sulfoxidation (SO) pathways will be presented.Recent data from freshly isolated mouse hepatocytes (FIMHs) confirmed previous in vivo results in rodents that Met TM is a detoxification pathway while Met TA leads to toxicity. Gender-related differences in Met accumulation and metabolism in FIMHs correlated with gender differences in toxicity. Data obtained from FIMHs also implicated Met SO in Met metabolism and toxicity. Currently, little is known about the mechanisms and biological significance of Met sulfoxidation in humans.In hypermethionemic patients, clinical and dietary interventions should focus on increasing Met TM and decreasing Met TA and SO. Novel biomarkers of hypermethionemia in humans that correlate with pathological end points are needed to better understand the impact of the condition.

SUBMITTER: Dever JT

PROVIDER: S-EPMC2957509 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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The biochemical and toxicological significance of hypermethionemia: new insights and clinical relevance.

Dever Joseph T JT Elfarra Adnan A AA

Expert opinion on drug metabolism & toxicology 20100928 11

<h4>Importance of the field</h4>Disrupted l-methionine (Met) metabolism can lead to hepatic, neurological and cardiovascular dysfunction in humans. Aberrant methyl group flux likely contributes to the development of these pathologies, but when patients also become hypermethionemic, additional toxicological mechanisms may be relevant.<h4>Areas covered in this review</h4>Following a discussion of the causes of hypermethionemia in humans, evidence for the toxicological roles and clinical significan ...[more]

PMID: 20874374

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The biochemical and toxicological significance of hypermethionemia: new insights and clinical relevance.

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The biochemical and toxicological significance of hypermethionemia: new insights and clinical relevance.

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