Effect of liver cirrhosis on phenylalanine and tyrosine metabolism.
OBJECTIVE
Phenylalanine conversion to tyrosine (i.e., 'hydroxylation') is the first irreversible step in phenylalanine catabolism and a source of circulating tyrosine. The purpose of the present review is both to examine hydroxylation from a biochemical standpoint and to report data measured in vivo under physiological conditions, as well as in liver and kidney disease.


RESULTS
The simultaneous infusion of phenylalanine and tyrosine tracers in humans allows us to determine the hydroxylation rate in vivo. Hydroxylation accounts for a minor ( approximately 10-20%) although significant portion of tyrosine flux. The liver and the kidney are the key organs accounting for virtually the whole-body hydroxylation rates. It is regulated by substrate availability, being acutely stimulated by mixed meal ingestion and by dietary adaptation to high phenylalanine intakes. Theoretically, it may be impaired in advanced liver and kidney disease. Nevertheless, in compensated liver cirrhosis, hydroxylation as well as tyrosine flux are not decreased but rather increased. Only in end stage liver disease hydroxylation may be impaired and is corrected by transplantation. Hydroxylation is also reduced in end stage renal disease.


CONCLUSIONS
Phenylalanine hydroxylation in vivo appears to represent a regulatory step of phenylalanine disposal and tyrosine production under acute and/or extreme conditions.
Tessari
Paolo
P
Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy. paolo.tessari@unipd.it
Vettore
Monica
M
Millioni
Renato
R
Puricelli
Lucia
L
Orlando
Rocco
R
D006801:Humans; D006900:Hydroxylation; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D014443:Tyrosine; D010649:Phenylalanine