Urinary ortho-tyrosine excretion in diabetes mellitus and renal failure: evidence for hydroxyl radical production.
BACKGROUND
Phenylalanine is converted to para- and ortho-tyrosine by hydroxyl free radical, or to para-tyrosine by the phenylalanine hydroxylase enzyme. The aim of this study was to measure para- and ortho-tyrosine in the urine and plasma of patients with chronic renal disease and/or diabetes, to obtain information on the renal handling of the different tyrosine isomers and, furthermore, to measure urinary levels of 8-epi-prostaglandin-F(2alpha), a marker of lipid peroxidation.


METHODS
In our cross-sectional study we measured para-, ortho-tyrosine, and phenylalanine levels, using high performance liquid chromatography and 8-epi-prostaglandin-F(2alpha) with enzyme-linked immunosorbent assay (ELISA). We compared 4 groups: (1) controls (CONTR, N = 14), (2) patients with chronic kidney disease (CKD, N = 12), (3) patients with type 2 diabetes mellitus (DIAB, N = 17), (4) patients with chronic kidney disease and type 2 diabetes (DIAB-CKD, N = 19).


RESULTS
We found a decreased plasma para-tyrosine level and decreased urinary para-tyrosine excretion in CKD patients, while the fractional excretion of para-tyrosine was similar in all 4 groups, approximately 1%. There was no difference in the plasma ortho-tyrosine levels between the groups. However, urinary ortho-tyrosine excretion was higher in all 3 groups of patients than in the CONTR group, and higher in DIAB and in DIAB-CKD patients than in CKD patients. The fractional excretion of ortho-tyrosine was significantly higher in DIAB and in DIAB-CKD patients than in the CONTR group. The fractional excretion of ortho-tyrosine exceeded 100% in the 2 diabetic groups. Urinary 8-epi-prostaglandin-F(2alpha)/creatinine ratio did not correlate with urinary ortho-tyrosine excretion.


CONCLUSIONS
The difference between para-tyrosine levels of the groups is probably due to renal impairment, while there is indirect evidence for an increased tubular secretion or production of ortho-tyrosine in the kidney in diabetic patients with or without CKD.
Molnár
Gergõ A
GA
Second Department of Medicine and Nephrological Center, University of Pécs, Medical Faculty, Hungary.
Wagner
Zoltán
Z
Markó
Lajos
L
Kó Szegi
Tamás
T
Mohás
Márton
M
Kocsis
Béla
B
Matus
Zoltán
Z
Wagner
László
L
Tamaskó
Mónika
M
Mazák
István
I
Laczy
Boglárka
B
Nagy
Judit
J
Wittmann
István
I
D000368:Aged; D003430:Cross-Sectional Studies; D003928:Diabetic Nephropathies / Q000097:blood / Q000652:urine*; D005260:Female; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D014443:Tyrosine / Q000097:blood / Q000737:chemistry / Q000652:urine*
D017665:Hydroxyl Radical; D014443:Tyrosine; D010649:Phenylalanine; C026741:2-tyrosine