BIOSYNTHESIS AND FUNCTION OF TETRAHYDROBIOPTERIN

Tetrahydrobiopterin (BH4) belongs to the class of pteridines (fused pyrimidopyrazines) possessing a 2-amino-4-oxo substitution of the pyrimidine moiety. BH4 is the coenzyme for tyrosine, tryptophan, and phenylalanine hydroxylases; for the glycerol ether monooxygenase; and probably for the arginine utilizing nitric oxide synthase in rodent macrophages. The function of BH4 in these reactions derives from the ability of the cofactor to react directly with molecular oxygen to form an active oxygen intermediate that can hydroxylate substrate. In the hydroxylation process, the coenzyme loses two electrons and is regenerated in vivo in an NADH-dependent reduction catalyzed by DHPR. This review of BH4 describes studies on biosynthesis, analysis, and the role of pterins in the immune response and in some diseases reported since our previous review. 1 For further general and more detailed information on BH4 and other pterins, the reader is referred to the monograph series Chemistry and Biology of Pteridines and the three-volume set Folates and Pterins.