New perspectives on folate transport in relation to alcoholism‐induced folate malabsorption – association with epigenome stability and cancer development

  title={New perspectives on folate transport in relation to alcoholism‐induced folate malabsorption – association with epigenome stability and cancer development},
  author={Abid Hamid and Nissar Ahmad Wani and Jyotdeep Kaur},
  journal={The FEBS Journal},
Folates are members of the B‐class of vitamins, which are required for the synthesis of purines and pyrimidines, and for the methylation of essential biological substances, including phospholipids, DNA, and neurotransmitters. Folates cannot be synthesized de novo by mammals; hence, an efficient intestinal absorption process is required. Intestinal folate transport is carrier‐mediated, pH‐dependent and electroneutral, with similar affinity for oxidized and reduced folic acid derivatives. The… 

The Concept of Folic Acid in Health and Disease

Food folic acid fortification was introduced in many countries because of the observational data that folates have a protective effect against neural tube defects, ischemic events, and cancer, however, high physiological folate concentrations and folate overload may increase the risk of impaired brain development in embryogenesis.

Biochemical and Molecular Mechanisms of Folate Transport in Rat Pancreas; Interference with Ethanol Ingestion

The present study deals with the mechanistic insights of reduced folate absorption in pancreas during chronic alcoholism by studying the mechanisms of alcohol associated reduced folates uptake in male Wistar rats.

Decreased activity of folate transporters in lipid rafts resulted in reduced hepatic folate uptake in chronic alcoholism in rats

The chronic ethanol ingestion led to decreased folate uptake in liver, which was associated with the decreased number of transporter molecules in the lipid rafts that can be ascribed to the reduced synthesis of these transporters.

Alcohol-associated folate disturbances result in altered methylation of folate-regulating genes

The results showed that there was not any significant change in the activity of folate hydrolyzing enzyme GGH in ethanol-fed rats while there was significant down regulation in the expression of FPGS.

Adaptive transport of folic acid across renal epithelia in folate-deficient rats

Folate deficiency increased the renal brush border membrane and basolateral folate uptake by increasing the number of transporter molecules and the observed up-regulation of mRNA expression was also associated with a significant increase in RFC and PCFT expression at the protein level.

Regulatory mechanisms of intestinal folate uptake in a rat model of folate oversupplementation

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.

Genetic aspects of folate metabolism.

  • A. Molloy
  • Biology
    Sub-cellular biochemistry
  • 2012
There is increasing research into the importance of folate-derived one-carbon units for DNA and histone methylation reactions, which exert crucial epigenetic control over cellular protein synthesis.

Mechanism of intestinal folate transport during folate deficiency in rodent model

The observed upregulation was associated with significant increase in reduced folate carrier (RFC) and proton coupled folate transporter (PCFT) expressions, suggesting the transcriptional and translational regulation of folate uptake during folate deficiency.

Increased synthesis of folate transporters regulates folate transport in conditions of ethanol exposure and folate deficiency

Excessive alcohol consumption and dietary folate inadequacy are the main contributors leading to folate deficiency (FD). The present study was planned to study regulation of folate transport in



Down‐regulation of reduced folate carrier may result in folate malabsorption across intestinal brush border membrane during experimental alcoholism

The low folate uptake activity observed in ethanol‐fed rats was found to be associated with decreased serum and red blood cell folate levels, which might explain the observed jejunal genomic hypomethylation and offer possible mechanistic insights into folate malabsorption during alcoholism.

Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells.

Long-term oversupplementation with folate leads to a specific and significant down-regulation in intestinal and renal folate uptake, which is associated with a decrease in message levels of hRFC, PCFT/HCP1, and FR.

Molecular and cellular biology of the human reduced folate carrier.

  • L. Matherly
  • Biology
    Progress in nucleic acid research and molecular biology
  • 2001

Adaptive regulation of intestinal folate uptake: effect of dietary folate deficiency.

It is demonstrated, for the first time, that dietary folate deficiency leads to a marked upregulation in intestinal folate uptake and in the activity of folate hydrolase.

New perspectives on folate catabolism.

Folate catabolism is emerging as an important component in the regulation of intracellular folate concentrations and whole-body folate status and ferritin levels are elevated in most physiological states associated with increased folateCatabolism.

Reduced folate carrier: tissue distribution and effects of chronic ethanol intake in the micropig.

It is suggested that chronic ethanol exposure decreases the intestinal absorption of folic acid by altering the expression of RFC and consequently its transport kinetics in JBB, providing a mechanism for the clinical finding of reduced folic Acid absorption in chronic alcoholics.

Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement.

The modulation of these metabolic abnormalities by increasing folate intake suggests that folate requirements may be different in affected individuals (T/T) relative to normal (C/C) or heterozygous (C-T) individuals.

Decreased Expression of Transporters Reduces Folate Uptake across Renal Absorptive Surfaces in Experimental Alcoholism

Findings highlight the role of downregulation of RFC and FBP expression and provide mechanistic insight into the observed reduced folate transport efficiency at renal absorptive surfaces in alcoholism, which may result in low blood folate levels commonly observed in alcoholics.