Tetrahydrobiopterin biosynthetic pathway and deficiency.
It has been proven that the most common defect in the tetrahydrobiopterin biosynthesis is caused by 6-pyruvoyl tetrahydropterin synthase deficiency. The enzyme 6-pyruvoyl tetrahydropterin synthase consists of four identical subunits which convert dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin in the presence of magnesium. UV, NMR, and MS data prove that the enzyme catalyzes the elimination of triphosphate as well as the intramolecular rearrangement. The 6-pyruvoyl tetrahydropterin synthase activity was measured in fetal erythrocytes and together with the neopterin and biopterin measurements in amniotic fluid this enabled performing prenatal diagnosis of 6-pyruvoyl tetrahydropterin synthase deficiency. Peripheral tetrahydrobiopterin deficiency was shown to be due to an incomplete 6-pyruvoyl tetrahydropterin synthase deficiency or heterozygosity.
Niederwieser
A
A
Department of Pediatrics, University of Zurich, Switzerland.
Curtius
H C
HC
D000429:Alcohol Oxidoreductases / Q000172:deficiency*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000172:deficiency; D005260:Female; D006801:Humans; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000378:metabolism; D019761:Phosphorus-Oxygen Lyases; D011247:Pregnancy; D011296:Prenatal Diagnosis
D001708:Biopterins; D010649:Phenylalanine; D000429:Alcohol Oxidoreductases; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase; C003402:sapropterin