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Folate and vitamin B12

  • John M. Scott (a1)
  • DOI:
  • Published online: 01 February 2007

The folates are made up of a pterdine ring attached to a p-aminobenzoate and a polyglutamyl chain. The active form is tetrahydrofolate which can have C1 units enzymically attached. These C1 units (as a formyl group) are passed on to enzymes in the purine pathway that insert the C−2 and C−8 into the purine ring. A methylene group (−CH2−) attached to tetrahydrofolate is used to convert the uracil-type pyrimidine base found in RNA into the thymine base found in DNA. A further folate cofactor, i.e. 5-methyltetrahydrofolate, is involved in the remethylation of the homocysteine produced in the methylation cycle back to methionine. After activation to S-adenosylmethionine this acts as a methyl donor for the dozens of different methyltransferases present in all cells. Folate deficiency results in reduction of purine and pyrimidine biosynthesis and consequently DNA biosynthesis and cell division. This process is most easily seen in a reduction of erythrocytes causing anaemia. Reduction in the methylation cycle has multiple effects less easy to identify. One such effect is certainly on the nerve cells, because interruption of the methylation cycle causing neuropathy can also happen in vitamin B12 deficiency due to reduced activity of the vitamin B12-dependent enzyme methionine synthase (EC In vitamin B12 deficiency, blocking of the methylation cycle causes the folate cofactors in the cell to become trapped as 5-methyltetrahydrofolate. This process in turn produces a pseudo folate deficiency in such cells, preventing cell division and giving rise to an anaemia identical to that seen in folate deficiency.

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Corresponding author: Professor John M. Scott, fax +353 1677 2400, email
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R Carmel (1995) Malabsorption of food cobalamin. In Bailliere's Clinical Haematology, vol. 8, pp. 639655 [SM Wickramsinghe , editor]. London:Bailliere Tindall.

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AM Molloy , S Daly , JL Mills , PN Kirke , AS Whitehead , D Ramsbottom , M Conley , DG Weir & JM Scott (1997) Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red cell folates: Implications for folate intake recommendations. Lancet 349, 15911593.

JM Scott & DG Weir (1996) Homocysteine and cardiovascular disease. Quarterly Journal of Medicine 89, 561563.

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