Chronic alcoholism alters the transport characteristics of folate in rat renal brush border membrane

Abstract

Folic acid transport across the epithelial cell membrane of kidney tubules is an essential step for its reabsorption, conservation, and homeostasis in the body. We characterized [ 3H]-folic acid transport in renal brush border membrane vesicles after 12 weeks of chronic ethanol ingestion to rats. The results demonstrated that chronic ethanol administration decreased the renal tubular reabsorption by a mechanism which involved an increase in the value of K m and a decrease in V max. Importantly, ethanol feeding also interfered with disulfide bond status, temperature sensitivity, and Na + and divalent cation dependency of the transport process. The transport was transmembrane pH dependent, and ethanol did not have any effect on the pH optimum of the folate transport. The reduction in uptake in the ethanol-fed group was more pronounced at pH less than 6. In addition, the binding component was found to contribute to an appreciable extent to the total folate uptake; however, the amount of folate binding was less in the ethanol-fed group. Moreover, the folic acid analog methotrexate inhibited the transport to great degrees in control and ethanol-fed rats. These findings highlight the possible mechanism of renal disturbances of folate conservation during chronic alcoholism.