{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T19:47:01Z","timestamp":1778960821403,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[1997,11,1]],"date-time":"1997-11-01T00:00:00Z","timestamp":878342400000},"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":[[1997,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations P225L and P225R were identified in codon 225 of the gene for ornithine transcarbamylase (OTC) in two patients with the neonatal form of OTC deficiency. The mutations occur at a CpG dinucleotide and eliminate a unique MspI restriction site in exon 7 of the OTC gene. They do not alter existing splice sites or create new sites, as judged from the nucleotide sequence. Both mutations are associated with undetectable levels of OTC antigen in liver homogenates, and with either complete lack of OTC activity (P225R mutation) or very small residual activity (0.15% of normal in the P225L mutation). The residual activity observed with P225L exhibits normal pH dependence, little or no increases in the Km values for ornithine and carbamoyl phosphate and normal stability at either 37\u00b0C or, in the presence of 0.66 mol\/L urea, at 0\u00b0C. The latter conditions were used to examine whether the P225L mutation favours dissociation of the active OTC trimer. Given the normal stability and lack of tendency to dissociation of the mutant enzyme, it appears likely that the dramatic reduction in the level of OTC protein is due to inefficient conversion of the mutant OTC precursor polypeptide (pOTC) into the correctly localized, appropriately folded, mature enzyme trimer, suggesting degradation of pOTC in transit to the mitochondria.<\/jats:p>","DOI":"10.1023\/a:1005363600268","type":"journal-article","created":{"date-parts":[[2002,12,21]],"date-time":"2002-12-21T21:48:34Z","timestamp":1040507314000},"page":"769-777","source":"Crossref","is-referenced-by-count":8,"title":["Missense mutations in codon 225 of ornithine transcarbamylase (OTC) result in decreased amounts of OTC protein: A hypothesis on the molecular mechanism of the OTC deficiency"],"prefix":"10.1002","volume":"20","author":[{"given":"M. A.","family":"Garc\u00eda\u2010P\u00e9rez","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Citol\u00f3gicas Fundaci\u00f3n Valenciana de Investigaciones Biom\u00e9dicas and CSIC  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Climent","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Citol\u00f3gicas Fundaci\u00f3n Valenciana de Investigaciones Biom\u00e9dicas and CSIC  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Briones","sequence":"additional","affiliation":[{"name":"Institut de Bioqu\u00edmica Cl\u00ednica Corporaci\u00f3 Sanit\u00e0ria and CSIC  Cerdanyola de Vall\u00e9s Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. A.","family":"Vilaseca","sequence":"additional","affiliation":[{"name":"Institut de Bioqu\u00edmica Cl\u00ednica Corporaci\u00f3 Sanit\u00e0ria and CSIC  Cerdanyola de Vall\u00e9s Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Rod\u00e9s","sequence":"additional","affiliation":[{"name":"Institut de Bioqu\u00edmica Cl\u00ednica Corporaci\u00f3 Sanit\u00e0ria and CSIC  Cerdanyola de Vall\u00e9s Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Rubio","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Citol\u00f3gicas Fundaci\u00f3n Valenciana de Investigaciones Biom\u00e9dicas and CSIC  Valencia Spain"},{"name":"Instituto de Investigaciones Citol\u00f3gicas  C\/Amadeo de Saboya, 4 Valencia 46010 Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[1997,11]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4838(82)90136-4"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50731-1"},{"key":"e_1_2_1_4_1","first-page":"1187","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Brusilow SW","year":"1995"},{"key":"e_1_2_1_5_1","first-page":"371","article-title":"A rapid, batch method for purifying ornithine transcarbamylase based on affinity chromatography using immobilized transition\u2010state analog","volume":"3","author":"De Martinis ML","year":"1981","journal-title":"Biochem Int"},{"key":"e_1_2_1_6_1","volume-title":"Enzymes","author":"Dixon M","year":"1979"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00209398"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a122265"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00206063"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6372096"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90466-6"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)71513-5"},{"key":"e_1_2_1_13_1","volume-title":"Immunochemistry in Practice","author":"Johnstone A","year":"1987"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)34781-6"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.4049\/jimmunol.115.6.1617","article-title":"Rapid isolation of antigens from cells with a staphylococcal protein A\u2010antibody adsorbent","volume":"115","author":"Kessler SW","year":"1975","journal-title":"J Immunol"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-516301-9.50009-7"},{"key":"e_1_2_1_17_1","first-page":"284","article-title":"A single amino acid substitution within the mature sequence of ornithine aminotransferase obstructs mitochondrial entry of the precursor","volume":"57","author":"Kobayasi T","year":"1995","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-022X(84)90040-X"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/227680a0"},{"key":"e_1_2_1_20_1","first-page":"325","volume-title":"The Urea Cycle","author":"Nuzum CT","year":"1976"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/15.17.7155"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00849a004"},{"key":"e_1_2_1_23_1","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.4049\/jimmunol.135.5.3354","article-title":"Antibodies to the \u03b1\u2010subunit of insulin receptor from eggs of immunized hens","volume":"135","author":"Song CS","year":"1985","journal-title":"J Immunol"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380020304"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380050404"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380040109"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.32.9.680"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02185751"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.23.10762"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1385\/0-89603-126-8:427"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1023%2FA%3A1005363600268","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1023\/A%3A1005363600268","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T03:55:08Z","timestamp":1694750108000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1023\/A%3A1005363600268"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,11]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1997,11]]}},"alternative-id":["10.1023\/A:1005363600268"],"URL":"https:\/\/doi.org\/10.1023\/a:1005363600268","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,11]]}}}