Inhibition of Uric Acid Biosynthesis in Birds by o-Diazoacetyl-l-Serine (Azaserine) and 6-Diazo-5-Oxo-l-Norleucine (DON)

Abstract

Uric acid, the principal end product of nitrogen metabolism in birds, was measured in the plasma and urine of birds during intravenous infusion of solutions of glucose, saline and ammonium acetate. Ammonium acetate infusions increased the content of uric acid in plasma and urine. Administration of o-diazoacetyl-l-serine (azaserine) and 6-diazo-5-oxo-l-norleucine (DON) at ld₅₀ doses produced prompt and nearly complete inhibition of uric acid synthesis in chickens, pigeons and cormorants as demonstrated by a parallel fall in plasma and urine uric acid. This inhibition is due to a block in purine biosynthesis. The ability of birds to synthesize uric acid recovers within 12–24 hours in spite of delayed toxicity with 50% of birds dying in 3–5 days. There is a dissociation between the acute, transient effects of azaserine and DON on uric acid production and the slower evolution of a lethal effect.