Nitric oxide synthase and pteridine biosynthesis in Physarum polycephalum
Gabriele Werner-Felmayer, Georg Golderer, Peter Groebner, Ernst R. Werner
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria
Physarum polycephalum synthesizes tetrahydrobiopterin and folic acid (1), two pteridine compounds. Whereas tetrahydrobiopterin, a cofactor of aromatic amino acid hydroxylases and nitric oxide synthases (NOSs), is formed predominantly in animals, folic acid, required by all living creatures for nucleic acid biosynthesis, is produced in plants and bacteria but is a vitamin for animals. We cloned GTP cyclohydrolase I, the enzyme synthesizing a common precursor of tetrahydrobiopterin and folic acid, and NOS from Physarum. Physarum GTP cyclohydrolase I exon/intron organization and alternative splicing of its mRNA closely resemble the human rather than the Dictyostelium discoideum enzyme (2). Physarum NOS, the only non-animal NOS cloned so far, is highly similar to inducible NOS from animals concerning its binding motifs for cofactors (3), its biochemical characteristics (1) and its complex exon/intron structure. In terms of evolution, Physarum therefore seems to be more highly developed than one might expect from its primitive organization.
(1) Werner-Felmayer et al. (1994) Biochem. J. 304, 105-111.
(2) Golderer et al. (2001) Biochem. J. 355, 499-507.
(3) Golderer et al. (2001) Genes & Dev. 15, 1299-1309.
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Last modified: Tuesday, December 3, 2002