Abnormal Folate Polyglutamate Ratios in Untreated Pernicious Anaemia Corrected by Therapy

Abstract

The relative amounts of folate compounds having 1--3--, 4--, 5-- and 6--glutamic acid residues in the molecule were measured in red blood cells. The results were expressed in relation to methyltetrahydrofolate pentaglutamate (5-glutamic acid residues) which is the analogue present in highest concentration. When the concentration of pentaglutamate is given a value of 100 the relative concentration of folates with 1--3--, 4--, 5-- and 6--glutamic acid residues in control subjects are 48, 48, 100 and 50 respectively. In folate deficiency there is a fall in the relative amount of the short chain glutamic acid chain compounds in addition to having an overall fall in the amount of folate present, the values for 1--3, 4, 5 and 6 chain folates being 16, 14, 100 and 39. By contrast, in untreated pernicious anaemia there is an accumulation of the short chain folates as well as an overall fall in polyglutamate concentration and the relative concentrations were 72, 44, 100 and 30. Folate polyglutamate appears to be the active coenzyme and the reltive amounts of glutamic acid residues may serve to regulate the rate of enzyme activity. In pernicious anaemia the amount of enzyme is reduced and on this hypothesis the regulatory function impaired.

Making sense of laboratory tests of folate status: Folate requirements to sustain normality

“…2 existed in the literature of the late 1950s and early 1960s for the concept, stated 2 decades ago [7] that "vitamin BI2 may play a role in the transport of folate into all cells and/or retention of folate by cells as well as in utilization by cells." There are abnormal folate polyglutamate ratios in BI2 deficiency, corrected by B12 therapy [15]. In addition to primary and secondary folate deficiency, there is also selective folate deficiency in one cell line but not another [ The second stage of folate depletion is folate-deficient erythropoiesis (Fig.…”

“…This is a very active field of investigation. Current deliberations on folate requirements, in which this reviewer participated, will appear in the proceedings of a March [13][14][15][16][17][18][19][20][21][22]1985 Geneva meeting of a Joint Food and Agriculture Organization/ World Health Organization (FAO/WHO) Expert Group on Requirements of Vitamin A, Iron, Folate and Vitamin BIZ, anticipated to be published in the WHO Technical Report Series in 1987. The underlying chemistry and biochemistry of the folates was reviewed in 1982 [65], 1983 [66], 1984 [67], and 1986 [61].…”

Folate‐dependent Serine Synthesis in Lymphocytes from Controls and Patients with Megaloblastic Anaemia: the Effect of Therapy

“…It emphasizes that one of the main functions of vitamin B I 2 is to maintain normal folate coenzymes although whether it does so through the homocysteine-methionine path or by some other means, is open to debate (Das & Herbert, 1976;Perry & Chanarin, 1977).…”

Homogeneous Assay for Whole Blood Folate Using Photon Upconversion

“…Thus, the folic acid level of the red blood cells should be measured for folate deficiency diagnosis . The folates in red blood cells are in the form of polyglutamates, whereas in the plasma they are only found as monoglutamates, because of pteroylpoly-γ-glutamylcarboxy-peptidase, which deconjugates the polyglutamates. , The red blood cells contain ∼40 times the amount of folate compared to plasma . The whole blood folate comprises both red blood cell and plasma folates.…”