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Methionine toxicity in the rat in relation to hepatic accumulation of S-adenosylmethionine: prevention by dietary stimulation of the hepatic transsulfuration pathway.

Abstract：

: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.

journal_name

Arch Biochem Biophys

journal_title

Archives of biochemistry and biophysics

authors

Regina M,Korhonen VP,Smith TK,Alakuijala L,Eloranta TO

doi

10.1006/abbi.1993.1083

subject

Has Abstract

pub_date

1993-02-01 00:00:00

pages

598-607

issue

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(83)71083-0

journal_volume

300

pub_type

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Methionine toxicity in the rat in relation to hepatic accumulation of S-adenosylmethionine: prevention by dietary stimulation of the hepatic transsulfuration pathway.