DIFFERENT STEREOSPECIFIC PROTEIN-BINDING OF TETRAHYDROFOLATES TO HUMAN SERUM-ALBUMIN

The protein binding of the tetrahydrofolates folinic acid (FA) and its metabolite 5-methyltetrahydrofolic acid (5-MTHF) to human serum album in (HSA) is stereoselective. At therapeutically relevant concentration s of tetrahydrofolate (range, 5-100 mu M), the protein binding was ste reoselective to the (R)-isomers of FA and 5-MTHF. The binding of (R)-F A and (R)-5-MTHF was saturated at a concentration of 7% HSA [(R)-tetra hydrofolate bound, ca. 80%]. In contrast to (S)-FA, which was not boun d to HSA, (S)-5-MTHF was bound to 45% under physiological conditions. (R)-FA did not influence the protein binding of (S)-FA. Hypoalbuminemi a is common in patients with advanced colorectal cancer and affects di fferentially the protein binding of the diastereoisomers of FA and 5-M THF. Thus, an influence on the biochemical modulation of 5-fluorouraci l by tetrahydrofolates should be taken into consideration.