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 albumin (HSA) is stereoselective. At therapeutically relevant concentrations of tetrahydrofolate (range, 5-100 microM), the protein binding was stereoselective to the (R)-isomers of FA and 5-MTHF. The binding of (R)-FA and (R)-5-MTHF was saturated at a concentration of 7% HSA [(R)-tetrahydrofolate bound, ca. 80%]. In contrast to (S)-FA, which was not bound to HSA, (S)-5-MTHF was bound to 45% under physiological conditions. (R)-FA did not influence the protein binding of (S)-FA. Hypoalbuminemia is common in patients with advanced colorectal cancer and affects differentially the protein binding of the diastereoisomers of FA and 5-MTHF. Thus, an influence on the biochemical modulation of 5-fluorouracil by tetrahydrofolates should be taken into consideration.
Mader
R M
RM
Department of Internal Medicine I, University of Vienna, Austria.
Steger
G G
GG
Rizovski
B
B
Jakesz
R
R
Rainer
H
H
D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D006801:Humans; D007202:Indicators and Reagents; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013237:Stereoisomerism; D013763:Tetrahydrofolates / Q000097:blood* / Q000737:chemistry
D007202:Indicators and Reagents; D012709:Serum Albumin; D013763:Tetrahydrofolates