2 The BH4 is synthesised from guanosine triphosphate cyclohydrolase (GTPCH), 6-pyruvoyl-tetrahydropterin synthase (PTPS), sepiapterin reductase (SR) and is regenerated by dihydropteridine reductase
(DHPR) and pterin carbinolamine-4-dehydratase (PCD).
He had normal urinary pterins and dihydropteridine reductase activity.
Urine pterin and dihydropteridine reductase activity analysis should be routinely performed to rule out BH4 deficiency.
The following will concentrate on the enzymes that can affect BH4 levels and its relationship to histamine; Methyltetrahydrafolate reductase (MTHFR), dihydropteridine reductase
, dihydrofolate reductase (DHFR), and quinoid dihydropteridine reductase
(QDPR) heavily influence BH4 (tetrahydrobiopterin) synthesis and recycling.
After its oxidation in the 2 hydroxylase reactions, it is reduced back to the active form by the action of pterin-4[alpha]-carbinolamine dehydratase and dihydropteridine reductase (Fig.
Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyltetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase. Hum Mutat 2006; 27:870-8.
The determination of pterins, biogenic amine metabolites and aromatic amino acids in cerebrospinal fluid using isocratic reverse phase liquid chromatography with in series dual cell coulometric electrochemical and fluorescence detection: use in the study of inborn errors of dihydropteridine reductase and 5,10-methylenetetrahydrofolatye reductase.
The diseases identified to date include: tyrosine hydroxylase deficiency (TH deficiency); aromatic L-amino acid decarboxylase deficiency (ALADD or AADC); GTP-1 cyclohydrolase deficiency (dopa-responsive dystonia); dihydropteridine reductase
deficiency (DHPR); and succinic semialdehyde dehydrogenase deficiency (SSADH).
Two enzymes are responsible for the regeneration of B[H.sub.4] following oxidation by the amino acid mono-oxygenases: pterin-4a-carbinolamine dehydratase (EC 126.96.36.199) and dihydropteridine reductase (DHPR; EC 188.8.131.52; Fig.
Phenylketonuria due to a deficiency of dihydropteridine reductase. N Engl J Med 1975;293:785-90.
Biopterin in the CSF was borderline increased together with a low normal dihydropteridine reductase activity in blood (Dr.
Blau (University Children s Hospital Zurich, Clinical Chemistry and Biochemistry, Zurich, Switzerland) for pterin measurements in CSF and measurement of the dihydropteridine reductase activity, Dr.