Hamid Abid, Kaur Jyotdeep, Mahmood Akhtar
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Mol Cell Biochem. 2007 Oct;304(1-2):265-71. doi: 10.1007/s11010-007-9509-3. Epub 2007 May 25.
Folate plays a critical role in maintaining normal metabolic, energy, differentiation and growth status of all mammalian cells. The disturbances in body folate homeostasis such as intestinal malabsorption in alcoholism are well-known contributor to folate deficiency associated disorders. The study was sought to delineate the kinetic features of folate transport in intestinal absorptive epithelium that could highlight insights of malabsorption during alcoholism. We studied [(3)H]-folic acid transport in intestinal brush border membrane (BBM) after 3 months of ethanol administration at 1 g/kg body weight/day to rats. The results showed that the folate transport exhibited saturable kinetics and was pH, Na(+), temperature, divalent cation sensitive, besides -SH group(s) was/were found important in the folate transport system to be efficiently operative. Importantly, the decreased intestinal BBM folate transport in chronic alcoholism was associated with increased K (m) and decreased V (max) during alcoholism. In addition, S-S group status of the transporter and presence of Na(+ )at the absorptive site seems to be perturbed during ethanol ingestion. However, H(+)/folate(-) coupled transport provided the driving force for transport as pH optimum in acidic range was not altered during alcoholism. The inhibition constants of methotrexate and unlabelled folic acid revealed that the two analogues are handled differently by the folate transport system. In addition, the low activity of folate transport system during chronic ethanol exposure was associated with low RBC folate levels. Overall, these findings suggest that the deregulated folate transport kinetics might contribute to intestinal folate malabsorption in alcoholism.
叶酸在维持所有哺乳动物细胞的正常代谢、能量、分化和生长状态方面发挥着关键作用。体内叶酸稳态的紊乱，如酒精中毒时的肠道吸收不良，是导致叶酸缺乏相关疾病的常见原因。本研究旨在描绘肠道吸收上皮细胞中叶酸转运的动力学特征，以突出酒精中毒期间吸收不良的相关见解。我们对大鼠每天按1 g/kg体重给予乙醇，持续3个月后，研究了肠道刷状缘膜（BBM）中[³H] - 叶酸的转运情况。结果表明，叶酸转运呈现出饱和动力学，对pH、Na⁺、温度、二价阳离子敏感，此外还发现 -SH基团对叶酸转运系统的有效运作很重要。重要的是，慢性酒精中毒时肠道BBM叶酸转运的减少与酒精中毒期间K（m）增加和V（max）降低有关。此外，在摄入乙醇期间，转运体的S - S基团状态以及吸收部位Na⁺的存在似乎受到了干扰。然而，H⁺/叶酸⁻偶联转运为转运提供了驱动力，因为在酒精中毒期间酸性范围内的最佳pH并未改变。甲氨蝶呤和未标记叶酸的抑制常数表明，这两种类似物在叶酸转运系统中的处理方式不同。此外，慢性乙醇暴露期间叶酸转运系统的低活性与红细胞叶酸水平低有关。总体而言，这些发现表明，叶酸转运动力学失调可能导致酒精中毒时肠道叶酸吸收不良。
