Iron-dependent formation of homocysteine from methionine and other thioethers.

OBJECTIVE

We tested whether homocysteine is formed from methionine and other thioethers in vitro and in vivo, because methionine can be chemically demethylated to homocysteine.

DESIGN

In in vitro studies, chemical conversions of thioethers (methionine, S-adenosylhomocysteine and cystathionine) into homocysteine were measured under various aerobic conditions. In humans, oral methionine (0.17 mmol/kg body weight) loading tests with and without an oral iron dose (ferrous sulfate, 13 mumol/kg) were performed.

SETTING

A university setting in Birmingham, AL, USA.

SUBJECTS

A total of five healthy adult subjects volunteered.

RESULTS

The in vitro incubation of methionine, S-adenosylhomocysteine or cystathionine with chelated iron resulted in the formation of homocysteine. These conversions were iron- and pH-dependent (pH optima between 5.0 and 6.0) and it was also chelator-dependent. In humans, oral methionine loading tests resulted in a 45% increase in the area-under-the-curve for plasma total homocysteine concentrations, when iron was given together with methionine.

CONCLUSION

Our data suggest that iron-dependent chemical formation of homocysteine can occur in vivo, and contribute to the plasma total homocysteine pool, since this formation can occur ceaselessly. We hypothesize that plasma total homocysteine concentrations reflect, in part, non-protein-bound iron in the body.