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d ‐threo‐tetrahydrobiopterin is synthesized via 1′‐oxo‐2′‐ d ‐hydroxypropyl‐tetrahydropterin in Dictyostelium discoideum Ax2
Author(s) -
Choi Yong Kee,
Park Jung Soon,
Kong Jin Seon,
Morio Takahiro,
Park Young Shik
Publication year - 2005
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.2005.04.064
Subject(s) - dictyostelium discoideum , chemistry , tetrahydrobiopterin , dictyostelium , biochemistry , enzyme , cofactor , gene
The biosynthesis of d ‐threo‐tetrahydrobiopterin (DH4, tetrahydrodictyopterin) in Dictyostelium discoideum Ax2 was investigated through the mutant disrupted in the gene encoding sepiapterin reductase (SR) by insertional inactivation. The mutant cells, being completely devoid of SR protein, showed 18.1% of l ‐erythro‐tetrahydrobiopterin (BH4) and 0.6% of DH4 productions in the wild type cells. The mutant cells were also identified to excrete d ‐ and l ‐sepiapterin, which were presumed to originate from intracellular 1′‐oxo‐2′‐ d ‐hydroxypropyl‐ and 1′‐oxo‐2′‐ l ‐hydroxypropyl‐tetrahydropterin (H4‐pterin), respectively. Furthermore, in a coupled assay with Dictyostelium SR, the mutant cell extract exhibited a novel enzyme activity converting 6‐pyruvoyltetrahydropterin to 1′‐oxo‐2′‐ d ‐hydroxypropyl‐H4‐pterin. These results are clear demonstration of the in vivo synthesis of DH4 via 1′‐oxo‐2′‐ d ‐hydroxypropyl‐H4‐pterin as well as an alternative synthesis of BH4 and DH4 in the complete absence of SR.