{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:06:51Z","timestamp":1792084011179,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,12,22]],"date-time":"2008-12-22T00:00:00Z","timestamp":1229904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Patients with vitiligo accumulate up to 10<jats:sup>\u22123<\/jats:sup> mol\/L concentrations of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> in their epidermis, which in turn affects many metabolic pathways in this compartment, including the synthesis and recycling of the cofactor (6<jats:italic>R<\/jats:italic>)\u2010<jats:sc>l<\/jats:sc>\u2010erythro\u20105,6,7,8\u2010tetrahydrobiopterin (6BH<jats:sub>4<\/jats:sub>). <jats:italic>De novo<\/jats:italic> synthesis of 6BH<jats:sub>4<\/jats:sub> is dependent on the rate\u2010limiting enzyme GTP cyclohydrolase I (GTPCHI) together with its feedback regulatory protein (GFRP). This step is controlled by 6BH<jats:sub>4<\/jats:sub> and the essential amino acid <jats:sc>l<\/jats:sc>\u2010phenylalanine. In the study presented here we wanted to investigate whether H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> affects the GTPCHI\/GFRP cascade in these patients. Our results demonstrated concentration\u2010dependent regulation of rhGTPCHI where 100 \u03bcmol\/L H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> was the optimum concentration for the activation of the enzyme and &gt;300 \u03bcmol\/L resulted in a decrease in activity. Oxidation of GFRP and GTPCHI does not affect feedback regulation via <jats:sc>l<\/jats:sc>\u2010phenylalanine and 6BH<jats:sub>4<\/jats:sub>. In vitiligo a constant upregulation of 6BH<jats:sub>4<\/jats:sub><jats:italic>de novo<\/jats:italic> synthesis results from epidermal build up of <jats:sc>l<\/jats:sc>\u2010phenylalanine that is not controlled by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. Taking the results together, 6BH<jats:sub>4<\/jats:sub><jats:italic>de novo<\/jats:italic> synthesis is controlled by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> in a concentration\u2010dependent manner, but H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010mediated oxidation does not affect the functionality of the GTPCHI\/GFRP complex.<\/jats:p>","DOI":"10.1007\/s10545-008-0971-1","type":"journal-article","created":{"date-parts":[[2008,12,19]],"date-time":"2008-12-19T20:57:58Z","timestamp":1229720278000},"page":"86-94","source":"Crossref","is-referenced-by-count":7,"title":["H<sub>2<\/sub>O<sub>2<\/sub> increases <i>de novo<\/i> synthesis of (6<i>R<\/i>)\u2010<scp>L<\/scp>\u2010erythro\u20105,6,7,8\u2010tetrahydrobiopterin via GTP cyclohydrolase I and its feedback regulatory protein in vitiligo"],"prefix":"10.1002","volume":"32","author":[{"given":"B.","family":"Chavan","sequence":"first","affiliation":[{"name":"Clinical and Experimental Dermatology\/Department of Biomedical Sciences University of Bradford Bradford BD7 1DP UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Beazley","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Dermatology\/Department of Biomedical Sciences University of Bradford Bradford BD7 1DP UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"Wood","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Dermatology\/Department of Biomedical Sciences University of Bradford Bradford BD7 1DP UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Rokos","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Dermatology\/Department of Biomedical Sciences University of Bradford Bradford BD7 1DP UK"},{"name":"Institute for Pigmentary Disorders in Association with EM Arndt University of Greifswald\/Germany and University of Bradford Bradford BD7 1DP UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Ichinose","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics, Institute for Comprehensive Medical Science Fujita Health University Toyoake, Aichi 470\u20131192 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. U.","family":"Schallreuter","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Dermatology\/Department of Biomedical Sciences University of Bradford Bradford BD7 1DP UK"},{"name":"Institute for Pigmentary Disorders in Association with EM Arndt University of Greifswald\/Germany and University of Bradford Bradford BD7 1DP UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,12,22]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-2960-6_72"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8502995"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202X.2004.22230.x"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(77)90173-7"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.11.004"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.1968.15"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.022646999"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409440200"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrs.887"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2002.6727"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrs.1968"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2007.04.010"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2007.01.028"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8128228"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jidsp.5640189"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2001.00220.x"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.07.082"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.01.082"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2005.07.023"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0906-6705.2005.0266j.x"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5701100"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0732510.x"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.10.185"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.38501"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-008-0971-1","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1007\/s10545-008-0971-1","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-008-0971-1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T18:26:23Z","timestamp":1694802383000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-008-0971-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,12,22]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,2]]}},"alternative-id":["10.1007\/s10545-008-0971-1"],"URL":"https:\/\/doi.org\/10.1007\/s10545-008-0971-1","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,12,22]]}}}