{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:36:06Z","timestamp":1784640966047,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,10,19]],"date-time":"2016-10-19T00:00:00Z","timestamp":1476835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,10,19]],"date-time":"2016-10-19T00:00:00Z","timestamp":1476835200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The mainstay of therapy for phenylketonuria (PKU) remains dietary protein restriction. Developmental and neurocognitive outcomes for patients, however, remain suboptimal. We tested the hypothesis that mice with PKU receiving protein\u2010restricted diets would reveal disruptions of brain amino acids that shed light on these neurocognitive deficits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Phenylalanine hydroxylase\u2010deficient (PKU) mice and parallel controls (both wild\u2010type and heterozygous) were fed custom diets containing 18, 6, and 4 % protein for 3 weeks, after which tissues (brain, liver, sera) were collected for amino acid analysis profiling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Phenylalanine (phe) was increased in all tissues (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) of PKU mice and improved with protein restriction. In sera, decreased tyrosine (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) was corrected (defined as not significantly different from the level in control mice receiving 18 % chow) with protein restriction, whereas protein restriction significantly <jats:italic>increased<\/jats:italic> many other amino acids. A similar trend for increased amino acid levels with protein restriction was also observed in liver. In brain, the effects of protein restriction on large neutral amino acids (LNAAs) were variable, with some deficit correction (threonine, methionine, glutamine) and no correction of tyrosine under any dietary paradigm. Protein restriction (4 % diet) in PKU mice significantly <jats:italic>decreased<\/jats:italic> lysine, arginine, taurine, glutamate, asparagine, and serine which had been comparable to control mice under 18 % protein intake.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Depletion of taurine, glutamate, and serine in the brain of PKU mice with dietary protein restriction may provide new insight into neurocognitive deficits of PKU.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10545-016-9984-3","type":"journal-article","created":{"date-parts":[[2016,10,19]],"date-time":"2016-10-19T07:11:58Z","timestamp":1476861118000},"page":"227-235","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Multicompartment analysis of protein\u2010restricted phenylketonuric mice reveals amino acid imbalances in brain"],"prefix":"10.1002","volume":"40","author":[{"given":"Kara R.","family":"Vogel","sequence":"first","affiliation":[{"name":"Division of Experimental and Systems Pharmacology, College of Pharmacy Washington State University Pharmaceutical and Biomedical Sciences Building, Room 347, 412 E. Spokane Falls Blvd Spokane WA 99204 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erland","family":"Arning","sequence":"additional","affiliation":[{"name":"Kimberly H. Courtwright and Joseph W. Summers Institute of Metabolic Disease Baylor Research Institute Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodoro","family":"Bottiglieri","sequence":"additional","affiliation":[{"name":"Kimberly H. Courtwright and Joseph W. Summers Institute of Metabolic Disease Baylor Research Institute Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Michael","family":"Gibson","sequence":"additional","affiliation":[{"name":"Division of Experimental and Systems Pharmacology, College of Pharmacy Washington State University Pharmaceutical and Biomedical Sciences Building, Room 347, 412 E. Spokane Falls Blvd Spokane WA 99204 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,10,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.10"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2015.12.004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.03.023"},{"issue":"2","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1093\/brain\/awh354","article-title":"Long\u2010term changes in glutamatergic synaptic transmission in phenylketonuria","volume":"128","author":"Glushakov AV","year":"2005","journal-title":"Brain"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00024.2014"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2011.568655"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1026847"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2005.06.014"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0410-6"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-15126-7_31"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.01.015"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/rej.2014.1630"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","unstructured":"SchreiberJM PearlPL DustinI WiggsE BarriosE WassermannEM GibsonKM TheodoreWH(2016)Biomarkers in a taurine trial for succinic semialdehyde dehydrogenase deficiency.JIMD Rep.doi:10.1007\/8904_2015_524","DOI":"10.1007\/8904_2015_524"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2015.08.001"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-014-2458-4"},{"issue":"12","key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"e0143833","DOI":"10.1371\/journal.pone.0143833","article-title":"Large neutral amino acid supplementation exerts its effect through three synergistic mechanisms: proof of principle in phenylketonuria mice","volume":"10","author":"Vliet D","year":"2015","journal-title":"PLoS ONE"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.08.004"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9524-8"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2015.03.009"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2016.03.003"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0160892"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10545-016-9984-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10545-016-9984-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10545-016-9984-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-016-9984-3","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T08:49:04Z","timestamp":1694767744000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-016-9984-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,19]]},"references-count":21,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["10.1007\/s10545-016-9984-3"],"URL":"https:\/\/doi.org\/10.1007\/s10545-016-9984-3","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,19]]}}}