A pteroylpolyglutamate binds to tetramers in deoxyhemoglobin but to dimers in oxyhemoglobin.

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Abstract
The binding of a physiological concentration of pteroylhepta(glutamate) [human] to HbO2 and deoxyhemoglobin in large excess was measured by ultrafiltration. The variation of free to bound folate with Hb concentration showed that a single molecule of the pteroylpolyglutamate is bound by deoxyhemoglobin tetramers and by .alpha..beta. dimers in HbO2. Although the binding sites are different, the affinity constants are the same and very similar to the 2,3-bisphosphoglycerate binding energy. In view of the small proportion of dimers in HbO2 much more pteroylhepta(glutate) is bound by deoxyhemoglobin over a wide range of Hb concentrations. Because even 2% deoxyhemoglobin is enough to bind all of the erythrocyte folate as polyglutamate, the bulk of it will be bound at physiological O2 pressures. Free folate could only be expected in fully oxygenated erythrocytes. The reaction of pteroylpolyglutamates with Hb represents an oxygenation-dependent storage mechanism that can account for the 40-fold excess of the vitamin in the erythrocyte over the amounts in the serum. Because methotrexate is also converted to polyglutamate derivatives in the erythrocytes, this drug is likely to be concentrated and stored there by the same mechanism.