Impairment of phenylalanine conversion to tyrosine in end-stage renal disease causing tyrosine deficiency.
BACKGROUND
Tyrosine is not considered an indispensable amino acid because in humans phenylalanine is converted to tyrosine. Recent human studies demonstrated that tyrosine production from phenylalanine occurs not only in liver but also in kidney.


METHODS
Here we report results from studies, performed in end-stage renal disease (ESRD) patients and in healthy controls using [15N] phenylalanine and [2H4] tyrosine as tracers demonstrating the mechanism of tyrosine deficiency in patients with renal failure.


RESULTS
Phenylalanine flux (an index of protein breakdown) was identical in both groups either before or during an infusion of amino acid mixture. In contrast, tyrosine flux (representing protein breakdown and tyrosine appearance from phenylalanine) and conversion of phenylalanine to tyrosine were lower in ESRD patients [2.05 +/- 0.30 micromol/kg fat-free mass (FFM)/hour and 2.59 +/- 0.52 micromol/kg FFM/hour, before and during amino acid infusion, respectively] than in the control subjects (4.07 +/- 0.54 micromol/kg FFM/hour and 5.53 +/- 0.86 micromol/kg FFM/hour, P <0.02, ESRD vs. controls, respectively). Plasma tyrosine concentrations in ESRD patients remained 40% lower than the controls during the postabsorptive state and following amino acid replacement.


CONCLUSIONS
We conclude that reduced conversion of phenylalanine to tyrosine causes tyrosine deficiency in patients with ESRD prompting to propose that tyrosine replacement is potentially required in patients with ESRD.
Boirie
Yves
Y
Endocrine Research Unit, Division of Endocrinology and Metabolism, and Nephrology Department, Mayo Clinicand Foundation, Rochester, Minnesota 55905, USA.
Albright
Robert
R
Bigelow
Maureen
M
Nair
K Sreekumaran
KS
D000328:Adult; D000368:Aged; D003903:Deuterium; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008875:Middle Aged; D009587:Nitrogen Isotopes; D010649:Phenylalanine / Q000097:blood / Q000493:pharmacokinetics*; D014443:Tyrosine / Q000097:blood / Q000172:deficiency* / Q000493:pharmacokinetics*
D007328:Insulin; D009587:Nitrogen Isotopes; D014443:Tyrosine; D010649:Phenylalanine; D007334:Insulin-Like Growth Factor I; D003903:Deuterium; D006854:Hydrocortisone