POLYUNSATURATED FATTY-ACIDS DECREASE THE APPARENT AFFINITY OF VITAMIN-D METABOLITES FOR HUMAN VITAMIN D-BINDING PROTEIN

POLYUNSATURATED FATTY-ACIDS DECREASE THE APPARENT AFFINITY OF VITAMIN-D METABOLITES FOR HUMAN VITAMIN D-BINDING PROTEIN
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DOI:
10.1016/0960-0760(92)90094-y
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发表时间:
1992-09-01
影响因子:
4.1
通讯作者:
VANBAELEN, H
VANBAELEN, H
中科院分区:
生物学2区
文献类型:
--
作者:
BOUILLON, R;XIANG, DZ;VANBAELEN, H

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在存在游离脂肪酸(FFA)、胆固醇、野牡丹素和几种药物的情况下,测定了来自血清的纯化人维生素D结合蛋白(DBP)对25-羟基维生素D3(25-OHD 3)和1-α,25-二羟基维生素D3 [1,25-(OH)2D 3]的亲和力。单不饱和脂肪酸和多不饱和脂肪酸显著降低25-OHD 3和1,25-(OH)2D 3对DBP的亲和力,而饱和脂肪酸(硬脂酸和花生酸)、胆固醇、胆固醇酯、视黄醇、视黄酸和藜芦醇(A1和E1)不影响表观亲和力。几种已知能降低甲状腺素与其血浆结合蛋白结合的化学物质并不影响DBP的亲和力。在36 μ M亚油酸或花生四烯酸存在下,DBP对25-OHD 3和1,25-(OH)2D 3的表观亲和力分别降低2.4- 4.6倍。只有FFA:DBP的摩尔比高于10,000才能使25-OHD 3与DBP的结合降低20%。然而,更小的FFA:DBP比例(花生四烯酸为25,油酸为45)降低了1,25-(OH)_2D_3与DBP的结合。后一种比例完全在生理范围内。以生理白蛋白:DBP摩尔比添加人血白蛋白不会损害亚油酸对[H-3]25-OHD 3与DBP结合的抑制作用。因此,维生素D代谢物的结合和生物利用度可能会被单不饱和脂肪酸和多不饱和脂肪酸改变,但不会被饱和脂肪酸改变。
The affinity of purified human vitamin D-binding protein from serum (DBP) for 25-hydroxyvitamin D3 (25-OHD3) and 1-alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] was measured in the presence of free fatty acids (FFA), cholesterol, prostaglandins and several drugs. Mono- and polyunsaturated fatty acids markedly decreased the affinity of both 25-OHD3 and 1,25-(OH)2D3 for DBP, whereas saturated fatty acids (stearic and arachidic acid), cholesterol, cholesterol esters, retinol, retinoic acid and prostaglandins (A1 and E1) did not affect the apparent affinity. Several chemicals known to decrease the binding of thyroxine to its plasma-binding protein did not affect the affinity of DBP.The apparent affinity of DBP for both 25-OHD3 and 1,25-(OH)2D3 decreased 2.4- to 4.6-fold in the presence of 36-mu-M of linoleic or arachidonic acid, respectively. Only a molar ratio of FFA:DBP higher than 10,000 was able to decrease the binding of 25-OHD3 to DBP by 20%. Much smaller ratio's of FFA:DBP (25 for arachidonic and 45 for oleic acid), however, decreased the binding of 1,25-(OH)2D3 to DBP. These latter ratio's are well within the physiological range. The addition of human albumin in a physiological albumin:DBP molar ratio did not impair the inhibitory effect of linoleic acid on the binding of [H-3]25-OHD3 to DBP. The binding and bioavailability of vitamin D metabolites thus might be altered by mono- and polyunsaturated but not by saturated fatty acids.