Phenylalanine hydroxylation across the kidney in humans - Rapid communication

Background. Although phenylalanine hydroxylase activity is detectable in in vitro renal tissue preparations, no data on in vivo phenylalanine hydroxyl ation across the human kidney, as well as on its possible contribution to w hole body hydroxylation. currently exist. Methods. To this aim, we have measured whole-body, renal, and splanchnic ph enylalanine hydroxylation to tyrosine, as well as phenylalanine and tyrosin e rates of appearance (Ra) and disposal (Rd), in postabsorptive subjects by means of renal and splanchnic arteriovenous catheterization combined with phenylalanine and tyrosine isotope infusions. Results. In the kidney, a relevant phenylalanine hydroxylation activity was detected (3.51 +/- 0.97 mu mol/min x 1.73 m(2) of body surface), whereas i t was 2.48 +/- 1.35 mu mol/min x 1.73 m(2) across the splanchnic area. Thes e two sites together accounted for virtually the entire whole-body phenylal anine hydroxylation. Renal production of tyrosine from phenylalanine hydrox ylation accounted for approximately 13% of whole-body tyrosine Ra, whereas renal total tyrosine Ra accounted for approximately 34% of whole body tyros ine Ra. In the splanchnic area, these figures were approximately 9 and 40%, respectively. Hydroxylation accounted for approximately 70% of phenylalani ne Rd in the kidney, as opposed to approximately 8% in the splanchnic area. Conclusions. These data indicate that hydroxylation represents the major ro ute of phenylalanine disposal within the kidney. The kidney and the splanch nic bed together account for all of the whole-body phenylalanine hydroxylat ion. These data also provide a further explanation for the reduced tyrosine pools occurring in uremia.