title: Mechanistic insights of intestinal absorption and renal conservation of folate in chronic alcoholism.
abstract: Folate mediated one-carbon metabolism is of fundamental importance for various cellular processes, including DNA synthesis and methylation of biological molecules. Due to the exogenous requirement of folate in mammals, there exists a well developed epithelial folate transport system for regulation of normal folate homeostasis. The intestinal and renal folate uptake is tightly and diversely regulated and disturbances in folate homeostasis like in alcoholism have pathological consequences. The study was sought to delineate the regulatory mechanism of folate uptake in intestine and reabsorption in renal tubular cells that could evaluate insights of malabsorption during alcoholism. The folate transporters PCFT and RFC were found to be associated with lipid rafts of membrane surfaces in intestine and kidney. Importantly, the observed lower intestinal and renal folate uptake was associated with decreased levels of folate transporter viz. PCFT and RFC in lipid rafts of intestinal and renal membrane surfaces. The decreased association of folate transporters in lipid rafts was associated with decreased protein and mRNA levels. In addition, immunohistochemical studies showed that alcoholic conditions deranged that localization of PCFT and RFC. These findings could explain the possible mechanistic insights that may result in folate malabsorption during alcoholism.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India.
authors.forename: Nissar Ahmad
authors.initials: NA
authors.lastname: Wani
authors.forename: Shilpa
authors.initials: S
authors.lastname: Thakur
authors.forename: Rauf Ahmad
authors.initials: RA
authors.lastname: Najar
authors.forename: Ritambhara
authors.initials: R
authors.lastname: Nada
authors.forename: Krishan Lal
authors.initials: KL
authors.lastname: Khanduja
authors.forename: Jyotdeep
authors.initials: J
authors.lastname: Kaur
mesh_terms: D000437:Alcoholism / Q000150:complications / Q000378:metabolism*; D000818:Animals; D004848:Epithelium / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism* / Q000502:physiology; D007408:Intestinal Absorption / Q000502:physiology*; D007422:Intestines / Q000737:chemistry; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D008286:Malabsorption Syndromes / Q000150:complications / Q000378:metabolism*; D008297:Male; D021962:Membrane Microdomains / Q000737:chemistry; D008871:Microvilli / Q000737:chemistry; D058979:Proton-Coupled Folate Transporter / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D058978:Reduced Folate Carrier Protein / Q000032:analysis / Q000378:metabolism
chemical_list: D058979:Proton-Coupled Folate Transporter; D058978:Reduced Folate Carrier Protein; D005492:Folic Acid