Hereditary xanthinuria. Evidence for enhanced hypoxanthine salvage.

Abstract

We tested the hypothesis that there is an enhanced rate of hypoxanthine salvage in two siblings with hereditary xanthinuria. We radiolabeled the adenine nucleotide pool with 18-'4Cladenine and examined purine nucleotide degradation after intravenous fructose. The cumulative excretion of radioactivity during a 5-d period was 9.7% and 9.1% of infused radioactivity in the enzymedeficient patients and 6.0±0.7% (mean±SE) in four normal subjects. Fructose infusion increased urinary radioactivity to 7.96 and 9.16 X 106 cpm/g creatinine in both patients and to 4.73±0.69 X 106 cpm/g creatinine in controls. The infusion of fructose increased total urinary purine excretion to a mean of 487% from low-normal baseline values in the patients and to 398±86% in control subjects. In the enzyme-deficient patients, the infusion of fructose elicited an increase of plasma guanosine from undetectable values to 0.7 and 0.9 gM. With adjustments made for intestinal purine loss, these data support the hypothesis that there is enhanced hypoxanthine salvage in hereditary xanthinuria. Degradation of guanine nucleotides to xanthine bypasses the hypoxanthine salvage pathway and may explain the predominance of this urinary purine compound in xanthinuria.

Molybdenum in Human Health and Disease

“…The fact that xanthine accumulation is much higher than the one of hypoxanthine suggests an increased salvage of hypoxanthine, which was experimentally proven by feeding studies using radio-labeled purines [ 26 ]. Given the relatively broad substrate specifi city, XOR can hydroxylate a number of exogenous substrates such as thiopurines, which are chemotherapeutics used for the treatment of acute lymphoblastic leukemia and autoimmune diseases [ 27 ].…”

Efficacy and safety of allopurinol in patients with hypoxanthine-guanine phosphoribosyltransferase deficiency

“…Uric acid and creatinine in plasma and urine were measured in a multichannel autoanalyzer (Modular P800, Roche, Mannheim, Germany; and Hitachi 704, Hitachi, Tokyo, Japan). Urinary hypoxanthine and xanthine were determined by high-performance liquid chromatography [8] while patients consumed a self-selected diet. Renal calculi were analyzed by infrared spectroscopy (Spectrum RXI FT-IR System, Perkin Elmer, Norwalk, CT).…”

“…(b) Biochemical abnormalities: purine metabolism was examined by the determination of plasma and urinary uric acid, creatinine, hypoxanthine, and xanthine [8], and, in some instances, by quantification of urinary radioactivity after the infusion of tracer doses of [8-14 C]adenine to radiolabel the adenine nucleotide pool [9]. (c) Enzyme deficiency: decreased HPRT activity in erythrocyte lysates and simultaneously increased adenine phosphoribosyltransferase (EC 2.4.2.7) activity [10].…”

Xanthine Oxidoreductase Function Contributes to Normal Wound Healing

“…Isolated XOR deficiency in humans is rare and is only documented in a few case reports (50,51). However, Mb cofactor deficiency has been described and is associated with severe refractory seizure activity with childhood fatality (reviewed in ref.…”