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Departments of Medicine and Chemistry, University of Vermont, Burlington, Vermont 05405
Methionine metabolism forms homocysteine via transmethylation.
Homocysteine is either 1) condensed to form cystathionine, which is cleaved to form cysteine, or 2) remethylated back
to methionine. Measuring this cycle with the use of isotopically labeled methionine tracers is problematic, because the tracer is
infused into and measured from blood, whereas methionine metabolism occurs inside cells. Because plasma homocysteine and cystathionine arise from intracellular metabolism of methionine, plasma homocysteine and cystathionine enrichments can be used to define intracellular methionine enrichment during an infusion of labeled methionine. Eight
healthy, postabsorptive volunteers were given a primed continuous infusion of [1-13C]methionine and
[methyl-2H3]methionine for 8 h. Enrichments in plasma methionine, [13C]homocysteine
and [13C]cystathionine were measured. In contrast to
plasma methionine enrichments, the plasma
[13C]homocysteine and [13C]cystathionine
enrichments rose to plateau slowly (rate constant: 0.40 ± 0.03 and 0.49 ± 0.09 h
1, respectively). The enrichment
ratios of plasma [13C]homocysteine to
[13C]methionine and [13C]cystathionine to
[13C]methionine were 58 ± 3 and 54 ± 3%,
respectively, demonstrating a large intracellular/extracellular
partitioning of methionine. These values were used to correct
methionine kinetics. The corrections increase previously reported rates
of methionine kinetics by ~40%.
homocysteine; methionine; kinetics; stable isotopes
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