Abnormal Folate Polyglutamate Ratios in Untreated Pernicious Anaemia Corrected by Therapy

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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 58 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 relative 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.