Wang X D, Krinsky N I, Russell R M
Gastrointestinal Nutrition Laboratory, USDA Human Nutrition Research Center, Boston, MA.
J Nutr. 1993 Jul;123(7):1277-85. doi: 10.1093/jn/123.7.1277.
When the plasma concentration of retinoic acid is increased, there is an accompanying reduction of circulating levels of retinol, suggesting that retinoic acid may have a regulatory effect on retinol metabolism in vivo. To determine which specific step(s) of retinol metabolism might be regulated by retinoic acid, retinol was incubated with ferret liver microsomes or cytosol with retinoic acid in vitro. Incubating the microsomal fraction with retinoic acid resulted in a dose-dependent (up to 0.5 mumol/L) decrease in the formation of retinal. On the contrary, no retinoic acid inhibitory effect was observed on retinal synthesis in the cytosol incubation, or in the cytosol plus microsome incubation. However, when retinoic acid was added to the cytosolic incubation mixture in the presence of the retinal oxidative inhibitor, citral, a dose-dependent inhibition of retinal synthesis was observed. Furthermore, the effect of retinoic acid on retinyl ester metabolism in ferret liver was studied by using endogenous retinyl esters of ferret liver as the substrate. When retinoic acid was added to the incubation mixture of microsomes plus cytosol, small, nonsignificant increases in retinol and retinyl esters were observed. When retinoic acid was added in the presence of citral, both the inhibition of retinol oxidation and the stimulation of retinol esterification were dose dependent up to approximately 0.3 mumol/L and then remained the same up to 1.0 mumol/L. These data strongly suggest that retinoic acid has a regulatory effect on retinol metabolism in ferret liver, which may occur via feedback inhibition of retinol oxidation and stimulation of retinol esterification.
当视黄酸的血浆浓度升高时，视黄醇的循环水平会随之降低，这表明视黄酸可能对体内视黄醇代谢具有调节作用。为了确定视黄醇代谢的哪些特定步骤可能受视黄酸调节，将视黄醇与雪貂肝脏微粒体或胞质溶胶在体外与视黄酸一起孵育。将微粒体部分与视黄酸孵育导致视黄醛形成呈剂量依赖性（高达0.5μmol/L）降低。相反，在胞质溶胶孵育或胞质溶胶加微粒体孵育中未观察到视黄酸对视黄醛合成的抑制作用。然而，当在视黄醛氧化抑制剂柠檬醛存在下将视黄酸添加到胞质溶胶孵育混合物中时，观察到视黄醛合成的剂量依赖性抑制。此外，以雪貂肝脏的内源性视黄酯为底物，研究了视黄酸对雪貂肝脏视黄酯代谢的影响。当将视黄酸添加到微粒体加胞质溶胶的孵育混合物中时，观察到视黄醇和视黄酯有小的、无统计学意义的增加。当在柠檬醛存在下添加视黄酸时，视黄醇氧化的抑制和视黄醇酯化的刺激在高达约0.3μmol/L时均呈剂量依赖性，然后在高达1.0μmol/L时保持不变。这些数据强烈表明视黄酸对雪貂肝脏中的视黄醇代谢具有调节作用，这可能通过对视黄醇氧化的反馈抑制和视黄醇酯化的刺激而发生。
