Hyperphenylalaninemia and pterin metabolism in serum and erythrocytes.
The relationship between blood phenylalanine concentrations and serum and erythrocyte biopterin and neopterin concentrations was investigated in 20 phenylketonuric patients with different dietary compliance. At serum phenylalanine concentrations ranging from 43 to 1004 mumol/l, a good correlation was found with serum biopterin (r = 0.76, P < 0.001) and with red blood cell biopterin (r = 0.62, P < 0.001). A similar correlation was found between serum neopterin and phenylalanine (r = 0.60, P < 0.001). The correlation between red blood cell neopterin and serum phenylalanine was less evident, however (r = 0.47, P < 0.005). After oral loading with phenylalanine (100 mg/kg body weight), serum and red blood cell biopterin concentrations increased in patients with classical phenylketonuria as well as in one patient with dihydropteridine reductase deficiency in response to the induced acute hyperphenylalaninemia. One patient suffering from 6-pyruvoyl tetrahydropterin synthase deficiency was loaded orally with tetrahydrobiopterin (20 mg/kg body weight). The kinetics of administered cofactor confirmed its rapid absorption, with early increase of serum concentrations followed by its transport into the red blood cells. The half-life of biopterin was approximately 7 h in serum and 15 h in red blood cells. Because both values are less than the half-life of phenylalanine (20-30 h) in serum, biopterin measurement offers no advantage in monitoring dietary control in hyperphenylalaninemic patients.
Ponzone
A
A
Department of Pediatric Clinic, University of Torino, Italy.
Guardamagna
O
O
Spada
M
M
Ponzone
R
R
Sartore
M
M
Kierat
L
L
Heizmann
C W
CW
Blau
N
N
D000429:Alcohol Oxidoreductases / Q000172:deficiency; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D019798:Neopterin; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000097:blood* / Q000201:enzymology; D019761:Phosphorus-Oxygen Lyases; D011622:Pterins / Q000097:blood*
D011622:Pterins; D001708:Biopterins; D010649:Phenylalanine; D019798:Neopterin; D000429:Alcohol Oxidoreductases; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase; C003402:sapropterin