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Tetrahydrobiopterin is functionally distinguishable from tetrahydrodictyopterin in Dictyostelium discoideum Ax2
Author(s) -
Kim Hye Lim,
Park Mi Bi,
Park Young Shik
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.08.026
Subject(s) - dictyostelium discoideum , tetrahydrobiopterin , dihydrofolate reductase , dictyostelium , cofactor , biochemistry , biology , microbiology and biotechnology , chemistry , enzyme , gene
Dictyostelium discoideum Ax2 produces both l ‐erythro‐tetrahydrobiopterin (BH4) and its stereoisomer d ‐threo‐BH4 (DH4). The putative cofactor function of them for phenylalanine hydroxylase (PAH) was investigated through genetic manipulation and quantitative determination of pteridines. In addition to establishing that dihydropteridine reductase (DHPR) and dihydrofolate reductase (DHFR) constitute the regeneration pathway of both BH4 and DH4, the results suggested that BH4 is a preferential cofactor for PAH in vivo, not a secondary product of DH4, which functions mainly as an antioxidant. Our result also demonstrated that PAH may be essential for Dictyostelium growth in nature, and thus it appears that the organism has evolved a strategy to maintain BH4 level via regeneration pathway at the expense of DH4 under oxidative stress conditions.