Exclusive use of ring 2‐[13C]L‐histidine for carbon 2 of the purine ring in purine nucleotide biosynthesis (PNB) de novo in an adult human

Abstract

The ring 2‐carbon of histidine is a source of one‐carbon units (1‐C) carried by folate coenzymes. In theory, this would be metabolically available for carbons 2 (C2) and 8 (C8) of the purine ring in PNB. An adult male ingested 0.71 g of ring 2‐[13C]L‐histidine ?HCl ?H2O (98%, Cambridge Isotope), and the 13C enrichment of urinary uric acid at C2 and C8 of each void was measured by an LC/MS/MS method. The % 13C enrichment at C2 in 33 voids (3 days) ranged from 0.05 to 0.58 with rhythmicity. Means (±SD, number of voids) were 0.15 (±0.09, 12), 0.24 (±0.19, 10) and 0.28 (±0.19, 11) for days 1, 2, and 3, respectively and were greater than zero (P < 0.01). In contrast, the % 13C enrichment at C8 varied from ‐0.12 to 0.09 with the means of 0.00 (±0.06), ‐0.01 (±0.02) and 0.00 (±0.02), respectively and these were not different from zero (P > 0.05). Our data indicate that histidine, like formate, is a source of 1‐C utilized by aminoimidazolecarboxamide ribotide transformylase; thus, C2 is enriched. We reported that the 2‐carbon of glycine is utilized by glycinamide ribotide transformylase for C8 in humans. It is likely in humans that completion of PNB requires different carbon sources for C2 and C8 and that different organs play concerted roles. The seemingly wasteful catabolism of histidine, an essential amino acid, to glutamate, a non‐essential amino acid, may make metabolic sense, when 1‐C produced is used for an essential purpose such as PNB.