Tetrahydro‐6‐biopterin is associated with tetrahydro‐7‐biopterin in primary murine mast cells

Ziegler, Irmgard; Hültner, Lothar

doi:10.1016/0014-5793(92)80755-6

Cited by 17 publications

(12 citation statements)

References 19 publications

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“…The source temperature was 30°C, and the cone voltage was 30 V. Fractions I and II were dissolved in 30 l of 0.1 M ammonium hydroxide, and 30 l of 15% methanol in water, respectively, and injected onto a C-18 reverse-phase HPLC column leading into the mass spectrometer. For further identification of biopterin and of 7-oxobiopterin in Fractions II and III, respectively, the fractions were oxidized by alkaline permanganate, and the resulting pterin-6-carboxylic acids were separated by HPLC and fluorometrically detected as described previously (34).…”

Section: Methodsmentioning

confidence: 99%

Development of the Pteridine Pathway in the Zebrafish,Danio rerio

Ziegler¹,

McDonald²,

Heßlinger³

et al. 2000

Journal of Biological Chemistry

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In the zebrafish, the peripheral neurons and the pigment cells are derived from the neural crest and share the pteridine pathway, which leads either to the cofactor tetrahydrobiopterin or to xanthophore pigments. The components of the pteridine pattern were identified as tetrahydrobiopterin, sepiapterin, 7-oxobiopterin, isoxanthopterin, and 2,4,7-trioxopteridine. The expression of GTP cyclohydrolase I activity during the first 24-h postfertilization, followed by 6-pyruvoyl-5,6,7,8-tetrahydropterin synthase and sepiapterin reductase, suggest an early supply of tetrahydrobiopterin for neurotransmitter synthesis in the neurons and for tyrosine supply in the melanophores. At 48-h postfertilization, sepiapterin formation branches off the de novo pathway of tetrahydrobiopterin synthesis. Sepiapterin, via 7,8-dihydrobiopterin and biopterin, serves as a precursor for the formation of 7-oxobiopterin, which may be further catabolized to isoxanthopterin and 2,4,7-trioxopteridine. Neither 7,8-dihydrobiopterin nor biopterin is a substrate for xanthine oxidoreductase. In contrast, both of these compounds are oxidized at C-7 by a xanthine oxidase variant form, which is inactivated by KCN, but is insensitive to allopurinol. The oxidase and the dehydrogenase form of xanthine oxidoreductase as well as the xanthine oxidase variant have specific developmental patterns. It follows that GTP cyclohydrolase I, the formation of sepiapterin, and the xanthine oxidoreductase family control the pteridine pathway in the zebrafish.

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Section: Methodsmentioning

confidence: 99%

Development of the Pteridine Pathway in the Zebrafish,Danio rerio

Ziegler¹,

McDonald²,

Heßlinger³

et al. 2000

Journal of Biological Chemistry

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“…Since melanocytes have cytosolic PAH and TH activities while only TH and tyrosinase activities are present in the melanosomes, the presence of 7BH 4 in these organelles was very likely. To test this assumption, melanosomal extracts from two different melanoma cell lines were subjected to acidic oxidation prior to analysis via HPLC using the standardised methods from Ziegler and Hültner (1992). Figure 2 shows the quantitative separation of a 100 µl aliquot containing 1·35 mg protein of oxidised melanosomal extract.…”

Section: -Biopterin Is Present In Melanosomesmentioning

confidence: 99%

A novel mechanism in control of human pigmentation by β-melanocyte-stimulating hormone and 7-tetrahydrobiopterin

Spencer¹,

Chavan²,

Marles³

et al. 2005

Journal of Endocrinology

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The human skin holds the full machinery for proopiomelanocortin processing. The -melanocytestimulating hormone ( -MSH)/melanocortin-1-receptor cascade has been implicated as a major player via the cAMP signal in the control of melanogenesis. Only very recently the -endorphin/µ-opiate receptor signal has been added to the list of regulators of melanocyte dendricity and melanin formation. In this context it was reported that (6R)--erythro-5,6,7,8-tetrahydrobiopterin (6BH 4 ) can act as an allosteric inhibitor of tyrosinase, the key enzyme in melanogenesis, and this inhibition is reversible by both -and -MSH. It was also shown earlier that 7BH 4 , the isomer of 6BH 4 , is twice as active in this inhibition reaction. However, as yet it is not known whether 7BH 4 is indeed present in loco in the melanosome. We here provide evidence that this isomer is present in this organelle in a concentration range up to 50 10 6 M. Determination of -MSH in melanosomal extracts yielded 10 pg/mg protein. Moreover, we demonstrate reactivation of the 7BH 4 /tyrosinase inhibitor complex by -MSH, whereas -MSH failed to do so. Furthermore, we show intra-melanosomal -dopa formation from dopachrome by 7BH 4 in a concentration range up to 134 10 6 M. Based on these results, we propose a new receptorindependent mechanism in the control of tyrosinase/ melanogenesis by -MSH and the pterin 7BH 4 .

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“…Reagents and Antibodies-The sources of all reagents that were used for cell cultivation (7,20) as well as for determination of enzymatic activities and for protein and biopterin determination (7,(21)(22)(23)(24) Generation of Monoclonal Antibodies to Murine GTP Cyclohydrolase I-Monoclonal antibodies were generated by immunizing Lou/C rats with a bacterially expressed murine GTP cyclohydrolase I fused in frame with Escherichia coli maltose binding protein (MGTP-maltose binding protein) (25). The procedure was essentially as described in Kremmer et al (26).…”

Section: Methodsmentioning

confidence: 99%

Phosphorylation of GTP Cyclohydrolase I and Modulation of Its Activity in Rodent Mast Cells

Heßlinger¹,

Kremmer²,

Hültner³

et al. 1998

Journal of Biological Chemistry

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GTP cyclohydrolase I controls the de novo pathway for the synthesis of tetrahydrobiopterin, which is the essential cofactor for tryptophan 5-monooxygenase and thus, for serotonin production. In mouse bone marrow-derived mast cells, the kit ligand selectively up-regulates GTP cyclohydrolase I activity (Ziegler, I., Hültner, L., Egger, D., Kempkes, B., Mailhammer, R., Gillis, S., and Rödl, W. (1993) J. Biol. Chem. 268, 12544 -12551). Immunoblot analysis now confirms that this long term enhancement is caused by increased expression of the enzyme. Furthermore we show that GTP cyclohydrolase I is subject to modification at the post-translational level. In vivo labeling with [32 P]orthophosphate demonstrates that in primary mast cells and in transfected RBL-2H3 cells overexpressing GTP cyclohydrolase I, the enzyme exists in a phosphorylated form. Antigen binding to the high affinity receptor for IgE triggers an additional and transient phosphorylation of GTP cyclohydrolase I with a concomitant rise in its activity, and in consequence, cellular tetrahydrobiopterin levels increase. These events culminate 8 min after stimulation and can be mimicked by phorbol ester. The hyperphosphorylation is greatly reduced by the protein kinase C inhibitor Ro-31-8220. In vitro phosphorylation studies indicate that GTP cyclohydrolase I is a substrate for both casein kinase II and protein kinase C.

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Tetrahydro‐6‐biopterin is associated with tetrahydro‐7‐biopterin in primary murine mast cells

Cited by 17 publications

References 19 publications

Development of the Pteridine Pathway in the Zebrafish,Danio rerio

Development of the Pteridine Pathway in the Zebrafish,Danio rerio

A novel mechanism in control of human pigmentation by β-melanocyte-stimulating hormone and 7-tetrahydrobiopterin

Phosphorylation of GTP Cyclohydrolase I and Modulation of Its Activity in Rodent Mast Cells

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