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J. Biol. Chem., Vol. 261, Issue 4, 1582-1587, 02, 1986
JD Finkelstein and JJ Martin
We conducted a systematic evaluation of the effects of increasing levels of
dietary methionine on the metabolites and enzymes of methionine metabolism
in rat liver. Significant decreases in hepatic concentrations of betaine
and serine occurred when the dietary methionine was raised from 0.3 to
1.0%. We observed increased concentrations of S-adenosylhomocysteine in
livers of rats fed 1.5% methionine and of S-adenosylmethionine and
methionine only when the diet contained 3.0% methionine. Methionine
supplementation resulted in decreased hepatic levels of
methyltetrahydrofolate-homocysteine methyltransferase and increased levels
of methionine adenosyltransferase, betaine-homocysteine methyltransferase,
and cystathionine synthase. We used these data to simulate the regulatory
locus formed by the enzymes which metabolize homocysteine in livers of rats
fed 0.3% methionine, 1.5% methionine, and 3.0% methionine. In comparison to
the model for the 0.3% methionine diet group, the model for the 3.0%
methionine animals demonstrates a 12-fold increase in the synthesis of
cystathionine, a 150% increase in flow through the betaine reaction, and a
550% increase in total metabolism of homocysteine. The concentrations of
substrates and other metabolites are significant determinants of this
apparent adaptation.
Methionine metabolism in mammals. Adaptation to methionine excess
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