Measurement of intracellular sulfur amino acid metabolism in humans

Methionine metabolism forms homocysteine via transmethylation. Homocysteine is either 1) condensed to form cystathionine, which is cleaved to form cys teine, 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 metabol ism occurs inside cells. Because plasma homocysteine and cystathionine aris e from intracellular metabolism of methionine, plasma homocysteine and cyst athionine enrichments can be used to define intracellular methionine enrich ment during an infusion of labeled methionine. Eight healthy, postabsorptiv e volunteers were given a primed continuous infusion of [1-C-13]methionine and [methyl-H-2(3)]methionine for 8 h. Enrichments in plasma methionine, [C -13]homocysteine and [C-13]cystathionine were measured. In contrast to plas ma methionine enrichments, the plasma [C-13]homocysteine and [C-13]cystathi onine enrichments rose to plateau slowly (rate constant: 0.40 +/- 0.03 and 0.49 +/- 0.09 h(-1), respectively). The enrichment ratios of plasma [C-13]h omocysteine to [C-13]methionine and [C-13]cystathionine to [C-13]methionine were 58 +/- 3 and 54 +/- 3%, respectively, demonstrating a large intracell ular/extracellular partitioning of methionine. These values were used to co rrect methionine kinetics. The corrections increase previously reported rat es of methionine kinetics by similar to 40%.