Oxygenation alters red cell folate levels

Folate activity is consistently higher in deoxygenated than oxygenated human blood as measured by both radioassay and Lactobacillus casei growth. Red cell, but not serum, folate levels are rapidly mutable: when fully oxygenated, the mean red cell folate level of 15 samples was 489 ng/ml; after deoxygenation the mean rose to 553 ng/ml; following re‐oxygenation the mean returned to 488 ng/ml. Transport of folate across the red cell membrane apparently does not contribute to these changes in folate levels, since agents known to inhibit permeation (N‐ethyl‐maleimide, p‐chlormercuriphenyl sulfonic acid and ethacrynic acid) do not affect the rise with deoxygenation. Moreover, new synthesis of folate compounds seems unlikely, since the changes are observed in energy‐depleted cells. Instead, direct binding of folate to haemoglobin is suggested by experiments in which the rise with deoxygenation was not seen in red cells exposed to carbon monoxide or treated with cyanate. Similar changes also occur in vivo: canine red cell, but not serum folate levels are significantly higher (P < 0.05) in samples collected from five different veins compared with blood from the paired artery (carotid‐jugular, renal, mesenteric, splenic, femoral) of four animals. Thus red cell folate levels are predictably influenced by the levels of oxygenation of the erythrocyte both in vitro and in vivo, possibly by reversibly binding to haemoglobin.