title: Increase of GTP cyclohydrolase I activity in mononuclear blood cells by stimulation: detection of heterozygotes of GTP cyclohydrolase I deficiency.
abstract: An assay is described for GTP cyclohydrolase I activity in human mononuclear cells isolated from 20 ml of heparinized blood. The activity of this enzyme was low in unstimulated cells and increased 5-10 times after stimulation by phytohemagglutinin (formation of 0.8-1.3 pmol dihydroneopterin triphosphate/min per mg protein at 37 degrees C, n = 15) or mixed lymphocyte culture. No activity was detected in phytohemagglutinin-stimulated mononuclear cells of a patient with proven GTP cyclohydrolase I deficiency in liver; the samples from the father and mother of the patient showed 30 and 46%, respectively, of the mean of 15 healthy controls. In unstimulated cells, neopterin was the main component of the total intracellular pterins (after oxidation). After stimulation, dihydroneopterin triphosphate, measured as neopterin triphosphate by high performance liquid chromatography, was increased 10-30 times; neopterin and pterin were increased only 2- to 6-fold. Since the immunoreactive cells from this patient were unable to produce pterins and all immunological tests on the patient were normal, it is concluded that neither dihydroneopterin triphosphate, nor one of its metabolites are of primary importance for an immune reaction. The assay described can be used for the detection of heterozygotes of GTP cyclohydrolase I deficiency.
authors.forename: N
authors.initials: N
authors.lastname: Blau
authors.forename: P
authors.initials: P
authors.lastname: Joller
authors.forename: M
authors.initials: M
authors.lastname: Atarés
authors.forename: J
authors.initials: J
authors.lastname: Cardesa-Garcia
authors.forename: A
authors.initials: A
authors.lastname: Niederwieser
mesh_terms: D000619:Aminohydrolases / Q000097:blood*; D005260:Female; D006136:GTP Cyclohydrolase / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D006580:Genetic Carrier Screening; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000201:enzymology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D011622:Pterins / Q000097:blood
chemical_list: D010835:Phytohemagglutinins; D011622:Pterins; D000619:Aminohydrolases; D006136:GTP Cyclohydrolase