¹³C-Enrichment of Urinary Uric Acid after l-[Ring-2-¹³C]Histidine Dose in Adult Humans

We determined whether ring-2 carbon of histidine is folate-dependently transferred to carbons 8 (C₈) and/or 2 (C₂) in urinary uric acid in humans. Two adults collected each urine void for four days. Aliquots of urine for the first day were used for baseline values; then the subjects ingested 0.7 g (3.3 mmol) of l-[ring-2-¹³C]histidine and collected urine for three experimental days. Aliquots were analyzed for percentage ¹³C-content at C₂ and C₈ by a liquid-chromatography-mass spectrometry method. Percentage enrichment was determined by subtracting time-of-day paired baseline percentage ¹³C-content from experimental percentage ¹³C-content for each void. C₂ was predominantly ¹³C-enriched in the majority of voids. The percentage enrichments at C₂ for two subjects were 0.14 (±0.028 [SEM], n = 26) and 0.18 (±0.049, n = 21), whereas at C₈, they were 0.008 (±0.006) and −0.005 (±0.008), respectively. The mean C₂-enrichments were significantly greater than zero (p < 0.01), whereas those of C₈ were not (p > 0.2). The enrichment had a diurnal rhythm peaking in the morning. Our results may be useful in the estimation of the timing for the administration of drugs that interfere with purine nucleotide biosynthesis in the treatment of cancer and autoimmune disease. View Full-Text