title: The kidney is an important site for in vivo phenylalanine-to-tyrosine conversion in adult humans: A metabolic role of the kidney.
abstract: Synthesis of Tyr in the human body occurs by hydroxylation of the indispensable amino acid Phe. Until now, it was believed that in humans, this process was restricted to the liver, but we provide compelling evidence of production of Tyr from Phe in the kidney. To determine whether the human kidney produces Tyr, we measured Tyr balance, the Tyr appearance rate, and the Phe-to-Tyr conversion in 12 healthy human subjects by using [(15)N]Phe and [(2)H(4)]Tyr as tracers. Renal plasma flow was measured by using paraaminohippurate, and sampling from the femoral artery and renal veins was performed. The results were compared with those obtained in 12 control subjects undergoing hepatic vein catheterization and infusion of identical tracers. In all 12 subjects, there was a net uptake of Phe by the kidney (2.2 +/- 1.2 micromol/min), whereas Tyr was released (5.3 +/- 1.5 micromol/min). In contrast, there was a net uptake of both Phe (9.5 +/- 1.2 micromol/min) and Tyr (14.3 +/- 1.3 micromol/min) by the splanchnic bed. Phe conversion to Tyr occurred at a rate of 5.2 +/- 1.2 micromol/min in kidney and 3.0 +/- 0.7 micromol/min in the splanchnic bed. The kidney contributed a substantial amount of Tyr to the systemic circulation where the splanchnic bed was a net remover of Tyr. Our results demonstrate that the kidney is the major donor of Tyr to the systemic circulation by its conversion of Phe to Tyr. This observation may have important clinical implications for patients with both renal and hepatic disease, who may be at risk of Phe overloading and Tyr deficiency, and it should be considered when parenteral or enteral nutrients are administered rich in Phe and low in Tyr.
authors.affiliation: Endocrinology Research Unit, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
authors.forename: N
authors.initials: N
authors.lastname: Møller
authors.forename: S
authors.initials: S
authors.lastname: Meek
authors.forename: M
authors.initials: M
authors.lastname: Bigelow
authors.forename: J
authors.initials: J
authors.lastname: Andrews
authors.forename: K S
authors.initials: KS
authors.lastname: Nair
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D006900:Hydroxylation; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010649:Phenylalanine / Q000378:metabolism*; D010651:Phenylalanine Hydroxylase / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D012079:Renal Circulation; D013152:Splanchnic Circulation; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D011506:Proteins; D014443:Tyrosine; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase