Vitamin B12 Interaction with Folate or Folic Acid

One of the vitamin B12 – dependent enzymes, methionine synthase, functions in one of the two folate cycles – the methylation cycle. This cycle is necessary to maintain availability of the methyl donor S-adenosylmethionine; interruption reduces the wide range of methylated products. One such important methylation is that of myelin basic protein. Reductions in the level of S-adenosylmethionine seen in PA and other causes of vitamin B12 deficiency produce demyelination of the peripheral nerves and the spinal column, called subacute combined degeneration. This neuropathy is one of the main presenting conditions in PA. The other principal presenting condition in PA is a megaloblastic anaemia morphologically identical to that seen in folate deficiency. Disruption of the methylation cycle should cause a lack of DNA biosynthesis and anaemia.

Treatment with vitamin B12, if given intramuscularly, will reactivate methionine synthase, allowing myelination to restart. The trapped folate will be released and DNA synthesis and generation of red cells will cure the anaemia. Treatment with high concentrations of folic acid will treat the anaemia but not the neuropathy of PA. 

In humans the vitamin B12 – dependent enzyme methylmalonyl coenzyme A (CoA) mutase functions in the metabolism of propionate and certain of the amino acids, converting them into succinyl CoA, and in their subsequent metabolism via the citric acid cycle. It is clear that in vitamin B12 deficiency the activity of the mutase is compromised, resulting in high plasma or urine concentrations of methylmalonic acid (MMA), a degradation product of methylmalonyl CoA. In adults this mutase does not appear to have any vital function, but it clearly has an important role during embryonic life and in early development. Children deficient in this enzyme, through rare genetic mutations, suffer from mental retardation and other developmental defects.

References:

Weir, D.G. & Scott, J.M. 1999. Cobalamins Physiology, Dietary Sources and Requirements. In: Sadler M.J., Strain J.J., Caballero B., eds. Encyclopedia of Human Nutrition, 1: 394-401.

Weir, D.G. & Scott, J.M. 1999. In: Modern Nutrition in Health and Disease. Editors Shils M.E., Olson J.A., Shike M., & Ross A.C. Baltimore, USA. Willams and Wilkins.

Savage, D.G. & Lindenbaum, J. 1995. Neurological complications of acquired cobalamin deficiency: clinical aspects. In: Bailliere’s Clin. Haematol. Megaloblastic Anaemia Editor S.M. Wickramasinghe Vol. 8, pp 657-678. London, Bailliere Tindall.