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

@article{Hamid2009NewPO,
  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},
  year={2009},
  volume={276}
}
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… 

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  • 2012
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References

SHOWING 1-10 OF 142 REFERENCES

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.
...