Xanthopterin, a metabolic end product of the nonconjugated
pterins dihydrobiopterin and
tetrahydrobiopterin, is present in many organs and is known to inhibit the proliferation and growth of conconavalin-stimulated lymphocytes. We have developed a simple fluorometric method to measure
xanthopterin in the blood and have validated the method by high pressure liquid chromatography (HPLC). Serum levels were 14 +/- 7 nmol/l in normal subjects and 141 +/- 51 nmol/l in
hemodialysis patients (p < 0.02). Intermediate levels from patients with
renal insufficiency not on dialysis correlated with serum
creatinine levels (p < 0.001).
Xanthopterin (MW 179) was cleared by
hemodialysis at a slightly lower rate than
creatinine. It is bound to
protein, but the binding, 90 +/- 5% in normal subjects, is decreased in
uremia to 60 +/- 15%, p < 0.01. Red cell levels of
xanthopterin were five times higher than those of plasma in normal subjects (69 +/- 15 vs. 14 +/- 7 nmol/l, p < 0.001), but uremic patients had lower levels in red cells than in plasma (101 +/- 24 vs. 141 +/- 51 nmol/l, p < 0.05). Slight or moderate
hemolysis induced by mechanical stress increased plasma
xanthopterin levels by 35%, the effect being more pronounced when
hemolysis was severe. We conclude that
xanthopterin is increased and its binding to
protein is decreased in
chronic renal failure. The altered ratio of red cell/plasma
xanthopterin levels may reflect an abnormality of the red cell membrane in
uremia. We are conducting further studies to amplify our preliminary findings that
xanthopterin inhibits cellular growth in vitro.