Role of Vitamin B₁₂ in Folate Coenzyme Synthesis

Abstract

Normal red cells in man were found to contain predominantly folate pentaglutamates with smaller amounts of tetra- and hexapolyglutamates. There was no change in the type of polyglutamate present in red cells from patients with vitamin B12 deficiency and primary folate deficiency. In contrast to the fall in red cell polyglutamate concentration in vitamin B12 deficiency, there was a marked fall in short-chain folates in early folate deficiency (treated non-anaemic epileptics) and a fall in both short chain and long chain polyglutamates in patients with severe folate deficiency and megaloblastic anaemia. These differences in folate distribution within cells exclude a primary failure to transport methylfolate into cells as the lesion in vitamin B12 deficiency. The failure of folate polyglutamate synthesis in ivtamin B12 deficiency arises either from a failure to provide the proper substrate for polyglutamate synthesis or to a direct requirement for vitamin B12 for polyglutamate synthesis.

Relationship between methylmalonic acid, homocysteine, vitamin B12 intake and status and socio-economic indices, in a subset of participants in the British National Diet and Nutrition Survey of people aged 65 y and over

“…This is consistent with literature evidence that vitamin B 12 inadequacy is associated with failure of maintenance of intracellular folate polyglutamates, followed by leakage of monoglutamate folates out of the cells (Perry et al, 1976;Chanarin, 1979). In the NDNS survey, 15% of the free-living participants and 39% of institution-living ones had serum folate concentrations < 7 nmol=l, and similar proportions (8 and 16%, respectively) had red cell folate concentrations below 230 nmol=l (Finch et al, 1998).…”

Cobalamin Dependent Methionine Synthesis and Methyl‐Folate‐Trap in Human Vitamin B12 Deficiency

“…Thus, if there is uptake of CHO-H,PteGlu, there should, theoretically, also be uptake of CH,-H,PteGlu. Since vitamin B, deficient erythrocytes have normal intracellular concentrations of folate monoglutamates (Chanarin et a/, 1974;Perry et al, 1976), their entry into the cells seems independent of vitamin B12 although some impairment in their transport in vitamin BI deficiency cannot be entirely excluded. FIG 4.…”

“…2. Direct coba/arnin dependency off late polyglrrtarnate synthesis (Perry et a/, 1976). Reduced folate polyglutamate concentrations in vitamin €3, deficient cells may also be a secondary effect following the failure in the metabolism of the methyl groups because of low methionine-synthetase activity (Lavoie et nl, 1974).…”

“…This is supposed to lead to impairment of de nouo synthesis of purine and thymidine (Mangum ct al, 1969; Burke et a silber & Mansouri, 1971). Other vitamin BI2 dependent mechanisms have been postulated, e.g., membrane transport of folate compounds (Tisman & Herbert, 1973 ; Chanarin et al, 1974), polyglutamate synthesis (Perry et a!, 1976), or synthesis of thymidylatc synthetase (Haurani, 1973(Haurani, , 1976.…”

Abnormal Folate Polyglutamate Ratios in Untreated Pernicious Anaemia Corrected by Therapy

“…These have been described elsewhere (Perry et al, 1976). A haemolysate was prepared from washed red blood cells, folate analogues separated by running the haemolysate on a cellulose column and eluates assayed for folate activity by microbiological assay, after treating the fractions with plasma conjugase.…”