Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India.
Br J Nutr. 2011 Mar;105(6):827-35. doi: 10.1017/S0007114510004538. Epub 2010 Nov 23.
Folic acid is essential for numerous biological functions, ranging from nucleotide biosynthesis to the remethylation of homocysteine. Folic acid is unable to cross the biological membranes by simple diffusion, so there exists a well-developed epithelial folate transport system for the regulation of normal folate homeostasis in the intestine. Any perturbances in the folate uptake system might lead to a state of folate deficiency, which in turn is strongly associated with the risk of various cancers, birth defects and CVD. Countries with obligatory folate fortification of food (USA and Canada) have documented a significant decrease in neural tube defects in newborns. However, the effect of folate oversupplementation on the intestinal absorption of folic acid has not been studied. We studied the process of folate transport and the expression of folate transporters in the rat intestine after folate oversupplementation. Rats were oversupplemented with tenfold the normal requirement of folic acid for periods of 10 and 60 d. Folate uptake in intestinal brush-border membrane vesicles followed saturable kinetics with pH optimum at 5·5. Acute, but not chronic, folate oversupplementation led to a significant down-regulation in intestinal folate uptake at acidic pH optima and was associated with a decrease in Vmax without any significant change in the Km of the folate uptake process. The decrease in folate uptake was also associated with the down-regulation in the protein levels of major folate transporters, proton-coupled folate transporter (PCFT) and reduced folate carrier (RFC), without altering their mRNA levels. Hence, it was concluded that acute folate oversupplementation results in a significant decrease in intestinal folate uptake by down-regulating the expressions of RFC and PCFT, via some post-transcriptional or translational mechanisms.
叶酸对于多种生物功能至关重要，从核苷酸合成到同型半胱氨酸的再甲基化。叶酸无法通过简单扩散穿过生物膜，因此在肠道中存在着一种发达的上皮叶酸转运系统，用于调节正常的叶酸内稳态。叶酸摄取系统的任何干扰都可能导致叶酸缺乏，这反过来又与各种癌症、出生缺陷和心血管疾病的风险密切相关。强制对食物进行叶酸强化的国家（美国和加拿大）已经记录到新生儿神经管缺陷显著减少。然而，叶酸过度补充对肠道叶酸吸收的影响尚未得到研究。我们研究了叶酸过度补充后大鼠肠道中叶酸转运和叶酸转运蛋白的表达过程。大鼠在 10 和 60 天的时间里接受了十倍于正常叶酸需求的叶酸补充。肠刷状缘膜囊泡中的叶酸摄取遵循饱和动力学，最佳 pH 值为 5.5。急性而非慢性叶酸过度补充会导致在酸性 pH 最佳条件下肠道叶酸摄取的显著下调，与 Vmax 的降低有关，而叶酸摄取过程的 Km 没有任何显著变化。叶酸摄取的减少还与主要叶酸转运蛋白，质子偶联叶酸转运蛋白（PCFT）和还原叶酸载体（RFC）的蛋白水平下调有关，而其 mRNA 水平没有改变。因此，研究得出结论，急性叶酸过度补充会通过下调 RFC 和 PCFT 的表达，导致肠道叶酸摄取显著减少，这可能是通过一些转录后或翻译机制实现的。
