EFFECT OF METHIONINE LOADING ON 5-METHYLTETRAHYDROFOLATE, S-ADENOSYLMETHIONINE AND S-ADENOSYLHOMOCYSTEINE IN PLASMA OF HEALTHY

1. Elevated plasma homocysteine concentration, either in the fasting s tate or after methionine loading, is an independent risk factor for va scular disease in man. Methionine loading has been used to investigate impaired methionine metabolism, especially of the trans-sulphuration pathway, but most studies have focused on changes in homocysteine. 2. We investigated the effect of methionine excess on total plasma homocy steine, 5-methyltetrahydrofolate (which is the active form of folate i n the remethylation of homocysteine to methionine), S-adenosylmethioni ne (the first metabolite of methionine) and S-adenosylhomocysteine (th e demethylated product of S-adenosylmethionine) over 24 h in 12 health y subjects. 3. As well as the expected increase in homocysteine (from 8.0+/-1.3 to 32.6+/-10.3 mu mol/l, mean+/-SD P<0.001), S-adenosylmethi onine showed a significant transient increase (from 37.9+/-25.0 to 240 .3+/-109.2 nmol/l, P<0.001), which correlated well with homocysteine ( r(2)=0.92, P<0.001). 5-Methyltetrahydrofolate values decreased signifi cantly (from 23.2+/-7.2 to 13.1+/-2.9 nmol/l, P<0.01), and gradually r eturned to baseline levels after 24 h. No significant change over the time of measurement was found for S-adenosylhomocysteine. 4. The seque nce of metabolic changes observed in this study strongly suggests that a change in either homocysteine or S-adenosylmethionine may cause a r eduction in 5-methyltetrahydrofolate. This must be considered in evalu ating the relationship between folate and homocysteine in vascular dis ease. The metabolic relationships illustrated in this study should be evaluated in the search for pathogenetic mechanisms of mild hyperhomoc ysteinaemia and vascular disease.