Participation of Pterins and of a Pteridine Binding Variant of Alpha₁-Acid Glycoprotein in the Control of Lymphocyte Transformation and of Lymphoblast Proliferation

Abstract

Dihydroneopterin triphosphate is the first product of pterin synthesis from guanosine triphosphate. It is further metabolized to tetrahydrobiopterin via sepiapterin and dihydrobiopterin (1). The anabolic biopterin derivatives have been found to accumulate in blood cells during hemopoietic cell proliferation in Beagle dogs (2) and especially, to be a marker of increased proliferation during leukemias; in blasts high concentrations of biopterin were found (3) and neopterin has been identified in the medium of alloantigen-induced lymphocytes (4). - Furthermore from blood of patients with malignant diseases a pteridine binding variant of alpha₁-acid glycoprotein (AGP_M) has been characterized (5). The glycoprotein moiety differs from normal AGP in its secondary structure; the pteridine chromophore is bound by the sialic acid antennae, resulting in a decreased negative charge as compared to normal AGP (6). Blood biopterin and AGP_M levels followed during clinical cases (7) also suggest a participation of the pterin system in (hemopoietic) cell proliferation. These observations prompted us to screen the major intermediates of pterin metabolism to determine whether they are not only lymphocyte products but also whether they have an effect on lymphocyte transformation and lymphoblast proliferation.