Phenylalanine hydroxylation across the kidney in humans rapid communication.
Phenylalanine hydroxylation across the kidney in humans.


BACKGROUND
Although phenylalanine hydroxylase activity is detectable in in vitro renal tissue preparations, no data on in vivo phenylalanine hydroxylation across the human kidney, as well as on its possible contribution to whole-body hydroxylation, currently exist.


METHODS
To this aim, we have measured whole-body, renal, and splanchnic phenylalanine hydroxylation to tyrosine, as well as phenylalanine and tyrosine 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 micromol/min x 1.73 m2 of body surface), whereas it was 2.48 +/- 1. 35 micromol/min x 1.73 m2 across the splanchnic area. These two sites together accounted for virtually the entire whole-body phenylalanine hydroxylation. Renal production of tyrosine from phenylalanine hydroxylation accounted for approximately 13% of whole-body tyrosine Ra, whereas renal total tyrosine Ra accounted for approximately 34% of whole-body tyrosine Ra. In the splanchnic area, these figures were approximately 9 and 40%, respectively. Hydroxylation accounted for approximately 70% of phenylalanine Rd in the kidney, as opposed to approximately 8% in the splanchnic area.


CONCLUSIONS
These data indicate that hydroxylation represents the major route of phenylalanine disposal within the kidney. The kidney and the splanchnic bed together account for all of the whole-body phenylalanine hydroxylation. These data also provide a further explanation for the reduced tyrosine pools occurring in uremia.
Tessari
P
P
Department of Clinical Experimental Medicine, University of Padova, Italy. ptessari@ux1.unipd.it
Deferrari
G
G
Robaudo
C
C
Vettore
M
M
Pastorino
N
N
De Biasi
L
L
Garibotto
G
G
D000328:Adult; D003903:Deuterium; D005260:Female; D006499:Hepatic Artery / Q000737:chemistry; D006503:Hepatic Veins / Q000737:chemistry; D006801:Humans; D006900:Hydroxylation; D007668:Kidney / Q000737:chemistry / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D010649:Phenylalanine / Q000032:analysis / Q000378:metabolism*; D010651:Phenylalanine Hydroxylase / Q000378:metabolism*; D013152:Splanchnic Circulation / Q000502:physiology; D014443:Tyrosine / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D014511:Uremia / Q000378:metabolism
D014443:Tyrosine; D010649:Phenylalanine; D003903:Deuterium; D010651:Phenylalanine Hydroxylase