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H 2 O 2 increases de novo synthesis of (6 R )‐ <scp>L</scp> ‐erythro‐5,6,7,8‐tetrahydrobiopterin via GTP cyclohydrolase I and its feedback regulatory protein in vitiligo
- Source :
- Journal of Inherited Metabolic Disease. 32:86-94
- Publication Year :
- 2008
- Publisher :
- Wiley, 2008.
-
Abstract
- Patients with vitiligo accumulate up to 10(-3) mol/L concentrations of H(2)O(2) in their epidermis, which in turn affects many metabolic pathways in this compartment, including the synthesis and recycling of the cofactor (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (6BH(4)). De novo synthesis of 6BH(4) is dependent on the rate-limiting enzyme GTP cyclohydrolase I (GTPCHI) together with its feedback regulatory protein (GFRP). This step is controlled by 6BH(4) and the essential amino acid L-phenylalanine. In the study presented here we wanted to investigate whether H(2)O(2) affects the GTPCHI/GFRP cascade in these patients. Our results demonstrated concentration-dependent regulation of rhGTPCHI where 100 micromol/L H(2)O(2) was the optimum concentration for the activation of the enzyme and >300 micromol/L resulted in a decrease in activity. Oxidation of GFRP and GTPCHI does not affect feedback regulation via L-phenylalanine and 6BH(4). In vitiligo a constant upregulation of 6BH(4) de novo synthesis results from epidermal build up of L-phenylalanine that is not controlled by H(2)O(2). Taking the results together, 6BH(4) de novo synthesis is controlled by H(2)O(2) in a concentration-dependent manner, but H(2)O(2)-mediated oxidation does not affect the functionality of the GTPCHI/GFRP complex.
Details
- ISSN :
- 15732665 and 01418955
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Journal of Inherited Metabolic Disease
- Accession number :
- edsair.doi...........b2ba8459660a183ee3b3cf86862e85ce
- Full Text :
- https://doi.org/10.1007/s10545-008-0971-1