Dictyopterin, 6‐(d‐threo‐1,2‐dihydroxypropyl)‐pterin, a new natural isomer of l‐biopterin

Abstract

A major pterin was isolated by reverse-phase high-performance liquid chromatography from cellular extract of vegetative cells of Dictyostelium discoideum after perchloric deproteinization and oxidation with acidic iodine. This compound was characterized by its chromatographic behavior, its absorption and fluorescence properties, by its oxidation product with alkaline permanganate, by secondary ion mass spectrometry and by circular dichroism. The final identification was obtained by comparison with authentic materials. It is concluded that the major pterin of D. discoideum is the compound 6-(~-threo-l,2-dihydroxypropyl)-pterin. The name dictyopterin is proposed for this new natural isomer of L-biopterin.A pteridine pathway has been demonstrated during growth and development of Dictyostelium discoideum cells [I -31. The end-products of this pathway, lumazine (2,4-dihydroxypteridine) [2-41, isoxantholumazine (2,4,7-trihydroxypteridine) [2], and a lumazine-like compound [4] were observed in the extracellular medium [2 -41. The release of extracellular pteridines was correlated with the ability of the cells to aggregate [3 -51. Whether these compounds, their precursors or related compounds (Fig

The G alpha subunit G alpha 4 couples to pterin receptors and identifies a signaling pathway that is essential for multicellular development in Dictyostelium.

“…Whether it is produced by the same cells that express Ga4 or by another cell type is not known. Interestingly, Klein and co-workers have purified a newly discovered pterin, dictyopterin, from vegetative cells that has a structure very similar to monapterin (37). Consistent with our proposal that an endogenous folate or pterin is an essential signaling molecule, we note that D. discoideum expresses an extracellular folate deaminase during the multicellular stages (38) that would have the function of clearing the morphogen from the extracellular space or act as a sink for establishing a possible morphogen gradient within the organism.…”

Structural insights into the dual substrate specificities of mammalian andDictyosteliumdihydropteridine reductases toward two stereoisomers of quinonoid dihydrobiopterin

“…Up to now, DH 4 was only identified from vegetative cells of D. discoideum [11]. So, it will be still interesting to know that other DHPRs could also catalyze the conversion of q-DH 2 into DH 4 .…”

“…BH 4 not only exists in eukaryotes including mammals [6,7], but also in some bacteria as glycosides [8][9][10]. BH 4 is the most common form, but other stereoisomers such as D-threo-BH 4 (tetrahydrodictyopterin, DH 4 ) from Dictyostelium discoideum [11] and L-threo-BH 4 from Chlorobium tepidum [12] have also been detected.…”

“…The major pterin in D. discoideum is dictyopterin with only traces of biopterin derivatives and DH 4 is the better cofactor for phenylalanine hydroxylase (PAH) [11,13]. It was therefore presumed that D. discoideum DHPR (DicDHPR) is able to reduce both quinonoid (6R)-L-erythro-dihydrobiopterin (q-BH 2 ) and quinonoid (6R)-Dthreo-dihydrobiopterin (q-DH 2 ) back to BH 4 and DH 4 , respectively, using NADH as a coenzyme.…”

Control of 6-(d-threo-1′,2′-dihydroxypropyl) pterin (dictyopterin) synthesis during aggregation of Dictyostelium discoideum. Involvement of the G-protein-linked signalling pathway in the regulation of GTP cyclohydrolase I activity

“…More recently, a pteridine from cell extracts of D. discoideum was identified as 6-(-threo-1,2-dihydroxypropylpterin) (see Figure 1). It was named dictyopterin and represents a new naturally occurring isomer of -biopterin [28]. It was also shown that dictyopterin is deaminated by an extracellular pterin deaminase to -threo-1,2-dihydroxypropyl lumazine (-dictyolumazine) [29].…”