{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:49:53Z","timestamp":1790999393328,"version":"4.1.0"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,4,1]]},"abstract":"<jats:p>A number of neurodegenerative diseases are mediated by mutation-induced protein misfolding. The resulting genetic defects, however, are expressed in varying phenotypes. Of the several well-established glycolytic enzyme deficiencies, triosephosphate isomerase (TPI) deficiency is the only one in which haemolytic anaemia is coupled with progressive, severe neurological disorder. In a Hungarian family with severe decrease in TPI activity, two germ line-identical but phenotypically differing compound heterozygote brothers inherited two independent (Phe240 \u2192 Leu and Glu145 \u2192 stop codon) mutations. We have demonstrated recently [Orosz, Ol\u00e1h, Alvarez, Keser\u00fc, Szab\u00f3, W\u00e1gner, Kov\u00e1ri, Hor\u00e1nyi, Bar\u00f3ti, Martial, Holl\u00e1n and Ov\u00e1di (2001) Blood 98, 3106\u20133112] that the mutations of TPI explain in themselves neither the severe decrease in the enzyme activity characteristic of TPI deficiency nor the enhanced ability of the mutant enzyme from haemolysate of the propositus to associate with subcellular particles. Here we present kinetic (flux analysis), thermodynamic (microcalorimetry and fluorescence spectroscopy), structural (in silico) and ultrastructural (immunoelectron microscopy) data for characterization of mutant isomerase structures and for the TPI-related metabolic processes in normal and deficient cells. The relationships between mutation-induced TPI misfolding and formation of aberrant protein aggregates are discussed.<\/jats:p>","DOI":"10.1042\/bst0300030","type":"journal-article","created":{"date-parts":[[2005,1,31]],"date-time":"2005-01-31T12:57:50Z","timestamp":1107176270000},"page":"30-38","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Triosephosphate isomerase deficiency: a neurodegenerative misfolding disease"],"prefix":"10.1042","volume":"30","author":[{"given":"Judit","family":"Ol\u00e1h","sequence":"first","affiliation":[{"name":"Institute of Enzymology, Hungarian Academy of Sciences, Budapest, H-1518, P.O. Box 7, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Orosz","sequence":"additional","affiliation":[{"name":"Institute of Enzymology, Hungarian Academy of Sciences, Budapest, H-1518, P.O. Box 7, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy M.","family":"Keser\u00fc","sequence":"additional","affiliation":[{"name":"Chemical Works of Gedeon Richter Ltd., Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Kov\u00e1ri","sequence":"additional","affiliation":[{"name":"Chemical Works of Gedeon Richter Ltd., Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of General Zoology, University of E\u00f6tv\u00f6s Lor\u00e1nd, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Holl\u00e1n","sequence":"additional","affiliation":[{"name":"National Institute of Blood Transfusion, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Ov\u00e1di","sequence":"additional","affiliation":[{"name":"Institute of Enzymology, Hungarian Academy of Sciences, Budapest, H-1518, P.O. Box 7, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Society Transactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/30\/2\/30\/530712\/bst0300030.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/30\/2\/30\/530712\/bst0300030.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T20:00:33Z","timestamp":1637179233000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article\/30\/2\/30\/63526\/Triosephosphate-isomerase-deficiency-a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,4,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2002,4,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bst0300030","relation":{},"ISSN":["0300-5127","1470-8752"],"issn-type":[{"value":"0300-5127","type":"print"},{"value":"1470-8752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,4,1]]}}}