{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:09:37Z","timestamp":1781712577697,"version":"3.54.5"},"reference-count":131,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T00:00:00Z","timestamp":1574726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK104770 and R03DK099427"],"award-info":[{"award-number":["R01DK104770 and R03DK099427"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Wilson disease (WD) is a genetic copper overload condition characterized by hepatic and neuropsychiatric symptoms with a not well-understood pathogenesis. Dysregulated methionine cycle is reported in animal models of WD, though not verified in humans. Choline is essential for lipid and methionine metabolism. Defects in neurotransmitters as acetylcholine, and biogenic amines are reported in WD; however, less is known about their circulating precursors. We aimed to study choline, methionine, aromatic amino acids, and phospholipids in serum of WD subjects. Hydrophilic interaction chromatography-quadrupole time-of-flight mass spectrometry was employed to profile serum of WD subjects categorized as hepatic, neurologic, and pre-clinical. Hepatic transcript levels of genes related to choline and methionine metabolism were verified in the Jackson Laboratory toxic milk mouse model of WD (tx-j). Compared to healthy subjects, choline, methionine, ornithine, proline, phenylalanine, tyrosine, and histidine were significantly elevated in WD, with marked alterations in phosphatidylcholines and reductions in sphingosine-1-phosphate, sphingomyelins, and acylcarnitines. In tx-j mice, choline, methionine, and phosphatidylcholine were similarly dysregulated. Elevated choline is a hallmark dysregulation in WD interconnected with alterations in methionine and phospholipid metabolism, which are relevant to hepatic steatosis. The elevated phenylalanine, tyrosine, and histidine carry implications for neurologic manifestations and are worth further investigation.<\/jats:p>","DOI":"10.3390\/ijms20235937","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T10:57:27Z","timestamp":1574765847000},"page":"5937","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Dysregulated Choline, Methionine, and Aromatic Amino Acid Metabolism in Patients with Wilson Disease: Exploratory Metabolomic Profiling and Implications for Hepatic and Neurologic Phenotypes"],"prefix":"10.3390","volume":"20","author":[{"given":"Tagreed A.","family":"Mazi","sequence":"first","affiliation":[{"name":"Department of Nutrition, University of California Davis, 3135 Meyer Hall, One Shields Avenue, Davis, CA 95616, USA"},{"name":"Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav V.","family":"Sarode","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of California Davis, 4150 V Street, Suite 3500 Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Czlonkowska","sequence":"additional","affiliation":[{"name":"Second Department of Neurology, Institute of Psychiatry and Neurology, 02 957 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-9651","authenticated-orcid":false,"given":"Tomasz","family":"Litwin","sequence":"additional","affiliation":[{"name":"Second Department of Neurology, Institute of Psychiatry and Neurology, 02 957 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoungmi","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Department of Public Health Sciences, University of California Davis, One Shields Avenue, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noreene M.","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of California Davis, 4150 V Street, Suite 3500 Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Medici","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of California Davis, 4150 V Street, Suite 3500 Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0168-8278(00)00028-3","article-title":"The Wilson\u2019s disease gene and phenotypic diversity","volume":"34","author":"Riordan","year":"2001","journal-title":"J. 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