Disease relevance of Dihydroneopterin

• GTP cyclohydrolase I of Escherichia coli is a torus-shaped homodecamer with D5 symmetry and catalyzes a complex ring expansion reaction conducive to the formation of dihydroneopterin triphosphate from GTP [1].
• Crystal structure and reaction mechanism of 7,8-dihydroneopterin aldolase from Staphylococcus aureus [2].
• Based on our data we propose that 7,8-dihydroneopterin may be involved in the progression to higher stages of HTLV-1 associated disease [3].
• Crystal structure of the bifunctional dihydroneopterin aldolase/6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Streptococcus pneumoniae [4].
• An increased concentration of total neopterins (neopterin + dihydroneopterin) is also a significant marker in patients with HIV-1 infection [5].

Psychiatry related information on Dihydroneopterin

• Recombinant tomato GCHI formed dihydroneopterin triphosphate as reaction product, as do other GCHIs, but unlike these enzymes it did not show cooperative behavior and was inhibited by its substrate [6].

High impact information on Dihydroneopterin

• 6-Pyruvoyl tetrahydrobiopterin synthase catalyses the conversion of dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin, the second of three enzymatic steps in the synthesis of tetrahydrobiopterin from GTP [7].
• An open reading frame located at 69.0 kilobases on the Escherichia coli chromosome was shown to code for dihydroneopterin aldolase, catalyzing the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin in the biosynthetic pathway of tetrahydrofolate [8].
• A point mutation converts dihydroneopterin aldolase to a cofactor-independent oxygenase [9].
• Tax did not significantly augment 7,8-dihydroneopterin mediated apoptosis [3].
• Role of 7,8-dihydroneopterin in T-cell apoptosis and HTLV-1 transcription in vitro [3].

Chemical compound and disease context of Dihydroneopterin

• Compared to control experiments, neopterin enhanced toxicity of all reactive species tested except formaldehyde, while 7,8-dihydroneopterin reduced activity of hypochlorite and chloramine-T [10].
• In this study we investigated the impact of neopterin and 7,8-dihydroneopterin on the toxicity of reactive species, namely chloramine-T, H2O2, hypochlorite, nitrite, and formaldehyde, respectively [10].
• Using Escherichia coli guanosine triphosphate cyclohydrolase, dihydroneopterin triphosphate was synthesized from guanosine triphosphate and was compared with sepiapterin as a substrate for tetrahydrobiopterin formation in bovine adrenal medulla extracts [11].

Biological context of Dihydroneopterin

• Additionally, we demonstrate that 7,8-dihydroneopterin and hydrogen peroxide activate the type 1 human T-cell leukemia virus (HTLV-1) long terminal repeat (LTR) [3].
• FasA and FasB also share significant amino acid sequence similarity with bacterial dihydroneopterin aldolases [12].
• In addition, 7,8-dihydroneopterin was found to be effective in the activation of redox-sensitive transcription factors and in the induction of HIV-1 gene expression [13].
• 7,8-Dihydroneopterin-induced apoptosis in Jurkat T lymphocytes: a comparison with anti-Fas- and hydrogen peroxide-mediated cell death [14].
• Upon incubation with 5 mM 7,8-dihydroneopterin and 50 microM hydrogen peroxide over a period of 24 hr, bimodal kinetics were observed with peaks at 5.5 hr (7,8-dihydroneopterin, 13.1%; H2O2, 11.4%) and at 24 hr (7,8-dihydroneopterin, 11.2%; H2O2, 13.2%) [14].

Anatomical context of Dihydroneopterin

• We now report that increased concentrations of 7,8-dihydroneopterin may lead to enhanced apoptosis and disturbance of the redox-balance of human leukemic Jurkat T cells [3].
• However, human monocytes/macrophages form only a little H(4)-biopterin, but release neopterin/7,8-dihydroneopterin instead [15].
• Neopterin and 7,8-dihydroneopterin induce apoptosis in the rat alveolar epithelial cell line L2 [16].
• In cerebrospinal fluid of patients with cerebral infections, elevated concentrations of the pteridine compounds neopterin and 7,8-dihydroneopterin were detected [17].
• We show that neopterin, but not 7,8-dihydroneopterin, is a stimulus for iNOS gene expression in rat vascular smooth muscle cells in vitro [18].

Associations of Dihydroneopterin with other chemical compounds

• Purification and properties of the enzymes from Drosophila melanogaster that catalyze the conversion of dihydroneopterin triphosphate to the pyrimidodiazepine precursor of the drosopterins [19].
• The subunit fold of the enzyme is related to substructures of dihydroneopterin triphosphate epimerase, GTP cyclohydrolase I, and pyruvoyltetrahydropterin synthase, which are all involved in the biosynthesis of pteridine type cofactors, and to urate oxidase, although some members of that superfamily have no detectable sequence similarity [20].
• Biosynthesis of tetrahydrofolate in plants: crystal structure of 7,8-dihydroneopterin aldolase from Arabidopsis thaliana reveals a novel adolase class [20].
• GTP cyclohydrolase I catalyses the first committing step in the biosynthesis of the pterin moiety of folic acid: conversion of GTP to dihydroneopterin triphosphate [21].
• Two domains with amino-acid sequence similarity are required for dihydroneopterin aldolase function in the multifunctional folic acid synthesis Fas protein of Pneumocystis carinii [22].

Gene context of Dihydroneopterin

• This enzyme catalyzes conversion of 7,8-dihydroneopterin (DHN) to 6-hydroxymethyl-7,8-dihydropterin, and is encoded by the folB gene in Escherichia coli [23].
• In contrast to the cytomix, no iNOS gene expression and no NO release could be detected after incubation with neopterin or 7,8-dihydroneopterin [16].
• GTP cyclohydrolase I (GCH) catalyses the conversion of GTP to dihydroneopterin triphosphate, initiating the pteridine pathway [24].
• As a result, IL-1beta contributed significantly to the amount of BH4 produced (+40%) but concomitantly reduced the accumulation of the GTPCH intermediate, 7,8-dihydroneopterin triphosphate (-50%) [25].
• Our results imply that in combination with TNF alpha high concentrations of 7,8-dihydroneopterin enhances apoptosis due to oxidative stress on cells [26].

Analytical, diagnostic and therapeutic context of Dihydroneopterin

• Multiple sequence alignment of FasA and FasB with other dihydroneopterin aldolases highlights only three positions where the amino acid is invariable between all the predicted proteins [12].
• Different affinity chromatography ligands have been compared for the purification of guanosine triphosphate (GTP) cyclohydrolase I, an enzyme that catalyses the transformation of GTP into formate and dihydroneopterin triphosphate, the first metabolite in the biosynthetic pathway of the pterins [27].
• Spin trapping study of antioxidant properties of neopterin and 7,8-dihydroneopterin [28].
• Since the immunoreactive cells from this patient were unable to produce pterins and all immunological tests on the patient were normal, it is concluded that neither dihydroneopterin triphosphate, nor one of its metabolites are of primary importance for an immune reaction [29].
• In connection with this result we found that 7,8-dihydroneopterin can increase Fas ligand expression detected in Western blot analysis and promoter reporter assays [30].

References