Andreas Jerlich wrote:
> I'm interested in references concerning concentrations of methionine
> with toxic effects on human metabolism (oral intake, parenteral
> nutrition, ...) ???
Here are some relevant abstracts:
Arch Biochem Biophys 1993 Feb 1;300(2):598-607
Methionine toxicity in the rat in relation to hepatic accumulation of
S-adenosylmethionine: prevention by dietary stimulation of the hepatic
transsulfuration pathway.
Regina M, Korhonen VP, Smith TK, Alakuijala L, Eloranta TO
Department of Biochemistry and Biotechnology, University of Kuopio,
Finland.
Rats were fed toxic levels of methionine with or without simultaneous
dietary supplements of glycine and serine. Feed intake,
growth rate, and metabolite concentrations in intestine, plasma, liver,
skeletal muscle, and kidneys were monitored. Both toxic
amounts of methionine and supplemental glycine and serine affected the
tissue distribution of several amino acids resulting in
similar, opposite, and diet-specific effects on the parameters studied.
These changes were considered to be normal responses
of amino acid metabolism to diet and to reflect metabolite flows between
tissues. The feeding of toxic levels of methionine
resulted in the accumulation of methionine, taurine, and glutathione in
all tissues measured, but caused marked accumulation of
S-adenosylmethionine and its catabolites only in liver. Hepatic
accumulation of S-adenosylmethionine was accompanied by
40% stimulation of methionine adenosyltransferase and 40% repression of
spermine synthase over a 2-week period.
Simultaneous dietary supplements of glycine and serine combined with
toxic levels of methionine markedly stimulated hepatic
methionine catabolism. As a result, tissue distribution of methionine
and glutathione returned close to normal in all tissues
measured and accumulation of hepatic S-adenosylmethionine and its
catabolites was prevented. Concentrations of taurine in
liver, blood, and kidneys were further elevated, suggesting increased
conversion of methionine to taurine followed by urinary
excretion. These changes were accompanied by normalization of the above
enzyme activities and the absence of symptoms of
methionine toxicity. It was concluded that methionine toxicity is likely
to be linked to hepatic accumulation of
S-adenosylmethionine, resulting in liver dysfunction probably due to
nonenzymatic methylation of liver macromolecules.
Accumulation of tissue glutathione may also contribute to toxicity.
Ann Nutr Metab 1990;34(2):93-97
Excess dietary methionine decreases indices of copper status in the rat.
Strain JJ, Lynch SM
Biomedical Sciences Research Centre, University of Ulster, Antrim,
Northern Ireland.
Two groups (n = 5) of male weanling Wistar rats were housed individually
and fed copper (Cu)-deficient (0.5 mg Cu/kg) diets
either with or without methionine supplementation (18 g/kg) for 49 days.
Plasma caeruloplasmin (EC 1.16.3.1) and
erythrocyte superoxide dismutase (EC 1.15.1.1, CuSOD) activities were
measured in blood. Tissue Cu levels and the
activities of cytochrome c oxidase (EC 1.9.3.1, CCO) and CuSOD were
measured in the heart and liver. Hepatic activities of
the sulfhydryl-sensitive enzymes, creatine kinase (EC 2.7.3.2), fumarase
(EC 4.2.1.2) glutathione S-transferase (EC 2.5.1.18)
and lipoamide dehydrogenase (EC 1.6.4.3) were also measured. Apart from
cardiac CCO activity all of the measured indices
of Cu status were found to be significantly (p less than 0.05) decreased
in the methionine supplemented rats. Although
fumarase activity was significantly (p less than 0.05) decreased in the
methionine-supplemented animals compared with
controls, the activities of the other sulfhydryl-sensitive enzymes were
not significantly decreased. These results suggest that
some of the toxic effects of excess dietary methionine may be mediated
through interference with copper metabolism rather
than through the previously postulated inhibition of
sulfhydryl-sensitive enzymes by metabolites of methionine.
Free Radic Res Commun 1989;5(4-5):221-226
Increased hepatic lipid peroxidation with methionine toxicity in the
rat.
Lynch SM, Strain JJ
Biomedical Sciences Research Centre, University of Ulster, Jordanstown,
Newtownabbey, Northern Ireland.
Consumption of excess methionine by rats is known to cause membrane
damage, liver enlargement and accumulation of iron in
the spleen. In this study two groups (n = 5) of male, Wistar rats were
pair-fed either a methionine supplemented (20.0 g/kg) or
control (2.0 g/kg) diet for 7 weeks. Hepatic and erythrocyte copper-zinc
superoxide dismutase activities were significantly
reduced (P less than 0.05 and P less than 0.001 respectively) by
methionine supplementation while the activities of catalase (P
less than 0.01 and 0.05) and glutathione peroxidase (P less than 0.05)
were significantly increased. Methionine
supplementation also increased hepatic lipid peroxidation (P less than
0.01), as measured by the level of thiobarbituric acid
reactive substances, and iron (P less than 0.001) concentrations. These
changes are indicative of increased oxidative stress
resulting from methionine toxicity.
--Tom
Tom Matthews
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