Mader R M, Steger G G, Rizovski B, Jakesz R, Rainer H
Department of Internal Medicine I, University of Vienna, Austria.
J Pharm Sci. 1994 Sep;83(9):1247-9. doi: 10.1002/jps.2600830912.
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.
四氢叶酸亚叶酸（FA）及其代谢产物5-甲基四氢叶酸（5-MTHF）与人血清白蛋白（HSA）的蛋白结合具有立体选择性。在治疗相关浓度的四氢叶酸（范围为5-100 microM）下，蛋白结合对FA和5-MTHF的（R）-异构体具有立体选择性。（R）-FA和（R）-5-MTHF在7% HSA浓度下结合达到饱和[（R）-四氢叶酸结合，约80%]。与不与HSA结合的（S）-FA不同，（S）-5-MTHF在生理条件下结合率为45%。（R）-FA不影响（S）-FA的蛋白结合。低白蛋白血症在晚期结直肠癌患者中很常见，并且对FA和5-MTHF非对映异构体的蛋白结合有不同影响。因此，应考虑其对四氢叶酸对5-氟尿嘧啶生化调节的影响。
