Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Drug Metab Dispos. 2011 Aug;39(8):1406-14. doi: 10.1124/dmd.111.038406. Epub 2011 May 4.
UDP-glucuronosyltransferase (UGT) activity toward the flavonoid quercetin and UGT protein were characterized in three equidistant small intestine (SI) segments from 4-, 12-, 18-, and 28-month-old male Fischer 344 rats (n = 8/age) using villin to control for enterocyte content. SI microsomal intrinsic clearance of quercetin was increased 3- to 9-fold from 4 months in the proximal and distal SI at 12 and 18 months. Likewise, at 30 μM quercetin, SI microsomal glucuronidation activity was increased with age: 4.8- and 3.9-fold greater at 18 months than at 4 months. Quercetin UGT regioselectivity was not changed by age. The distal SI preferentially catalyzed glucuronidation at the 7-position, whereas the proximal SI produced the greatest proportion of 4'- and 3'-conjugates. Enterocyte UGT content in different SI segments was not consistently changed with age. In the proximal SI, UGT1A increased 64 and 150% at 12 and 18 months and UGT1A1, UGT1A7, and UGT1A8 were also increased at 12 and 18 months. However, age-related changes in expression were inconsistent in the medial and distal segments. Microsomal rates of quercetin glucuronidation and UGT expression were positively correlated with UGT1A1 content for all pooled samples (r = 0.467) and at each age (r = 0.538-0.598). UGT1A7 was positively correlated with total, 7-O- and 3-O-quercetin glucuronidation at 18 months. Thus, age-related differences in UGT quercetin glucuronidation depend on intestinal segment, are more pronounced in the proximal and distal segments and may be partially related to UGT1A1 and UGT1A7 content.
UDP-葡糖醛酸基转移酶（UGT）对类黄酮槲皮素的活性和 UGT 蛋白在来自 4 个月、12 个月、18 个月和 28 个月龄雄性 Fischer 344 大鼠的三个等距小肠（SI）段中进行了特征描述，使用绒毛蛋白来控制肠细胞含量。在近端和远端 SI 中，12 个月和 18 个月时，槲皮素的 SI 微粒体内在清除率增加了 3 至 9 倍。同样，在 30 μM 槲皮素的情况下，SI 微粒体中葡萄糖醛酸化活性随年龄增长而增加：与 4 个月龄相比，18 个月龄时增加了 4.8 至 3.9 倍。槲皮素 UGT 区域选择性不受年龄影响。远端 SI 优先催化 7 位的葡萄糖醛酸化，而近端 SI 产生的 4'-和 3'-缀合物比例最大。不同 SI 段的肠细胞 UGT 含量随年龄变化不一致。在近端 SI 中，UGT1A 在 12 个月和 18 个月时增加了 64%和 150%，UGT1A1、UGT1A7 和 UGT1A8 也在 12 个月和 18 个月时增加。然而，在中肠和远端段，与年龄相关的表达变化不一致。所有合并样本（r = 0.467）和每个年龄组（r = 0.538-0.598）的微团速率与 UGT1A1 含量呈正相关。UGT1A7 与 18 个月时的总、7-O-和 3-O-槲皮素葡萄糖醛酸化呈正相关。因此，UGT 槲皮素葡萄糖醛酸化与年龄相关的差异取决于肠段，在近端和远端段更为明显，可能与 UGT1A1 和 UGT1A7 含量部分相关。
