{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:21:51Z","timestamp":1791148911797,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,4,13]],"date-time":"2005-04-13T00:00:00Z","timestamp":1113350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2005,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lesch\u2013Nyhan disease (LND) is a rare disorder caused by a defect of an enzyme in the purine salvage pathway, hypoxanthine phosphoribosyl transferase (HPRT). It is still unknown how the metabolic defect translates into the complex neuropsychiatric phenotype characterized by self\u2010injurious behavior, dystonia and mental retardation. There are abnormalities in purine and pyrimidine nucleotide content in HPRT\u2010deficient cells. We hypothesized that altered nucleotide concentrations in HPRT deficiency change G\u2010protein\u2010mediated signal transduction. Therefore, our original study aim was to examine the high\u2010affinity GTPase activity of G\u2010proteins in membranes from primary human skin and immortalized mouse skin fibroblasts, rat B103 neuroblastoma cells and mouse Neuro\u20102a neuroblastoma cells. Unexpectedly, in membranes from human fibroblasts, B103\u2010 and Neuro\u20102a cells, <jats:italic>V<\/jats:italic><jats:sub>max<\/jats:sub> of low\u2010affinity nucleoside 5\u2032\u2010triphosphatase (NTPase) activities was decreased up to 7\u2010fold in HPRT deficiency. In contrast, in membranes from mouse fibroblasts, HPRT deficiency increased NTPase activity up to 4\u2010fold. The various systems analyzed differed from each other in terms of <jats:italic>K<\/jats:italic><jats:sub>m<\/jats:sub> values for NTPs, absolute <jats:italic>V<\/jats:italic><jats:sub>max<\/jats:sub> values and <jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> values for nucleoside 5\u2032\u2010[\u03b2,\u03b3\u2010imido]triphosphates. Our data show that altered membrane NTPase activity is a biochemical hallmark of HPRT deficiency, but species and cell\u2010type differences have to be considered. Thus, future studies on biochemical changes in LND should be conducted in parallel in several HPRT\u2010deficient systems.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2005.03151.x","type":"journal-article","created":{"date-parts":[[2005,6,21]],"date-time":"2005-06-21T21:42:49Z","timestamp":1119390169000},"page":"1579-1586","source":"Crossref","is-referenced-by-count":15,"title":["Altered membrane NTPase activity in Lesch\u2013Nyhan disease fibroblasts: comparison with HPRT knockout mice and HPRT\u2010deficient cell lines"],"prefix":"10.1111","volume":"93","author":[{"given":"Cibele S.","family":"Pinto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyder A.","family":"Jinnah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L.","family":"Shirley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L.","family":"Nyhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Seifert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,5,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:14:1-2:087"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00484403"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(98)01202-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(01)00141-3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)02290-X"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb17157.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02619607"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20020148"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211292200"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204259200"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb03488.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1523\/JNEUROSCI.14-03-01164.1994","article-title":"Dopamine deficiency in a genetic mouse model of Lesch\u2013Nyhan disease","volume":"14","author":"Jinnah H. 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