{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:46:19Z","timestamp":1791333979409,"version":"4.3.1"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,11,12]],"date-time":"2012-11-12T00:00:00Z","timestamp":1352678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NSF","award":["EF-1038593"],"award-info":[{"award-number":["EF-1038593"]}]},{"name":"NIH","award":["R01 ES019876"],"award-info":[{"award-number":["R01 ES019876"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec>\n                    <jats:title>Scope<\/jats:title>\n                    <jats:p>Folate status and the status of the methionine cycle are typically assessed by measuring folate and metabolites in the plasma. It is assumed that plasma metabolite levels are proportional to their levels in tissues, but there is little information to support this assumption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We developed a mathematical model, based on known kinetics of the methionine cycle in the liver and tissues, and the transport kinetics of metabolites into and out of the plasma. We use the model to explore the relationship between folate status and metabolite values in the plasma, the relationships between metabolite values and methylation capacity, the response to a methionine load, and the half\u2010life of folate in plasma and tissues. We also use the model to study the effects of Down syndrome and oxidative stress on metabolite values in plasma and tissues. The model accurately reproduces measured metabolite values pre\u2010 and post\u2010folate fortification. The model shows that a high acute intake of folate remains largely restricted to the plasma and is rapidly excreted; only a prolonged exposure to increased folate elevates tissue folate significantly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The model accurately reproduces experimental and clinical findings and can serve as a platform to study, in silico, the relationships between metabolite values in tissues and plasma, and how these vary with methionine and B vitamin input, and with mutations in the genes for enzymes in the methionine cycle.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mnfr.201200125","type":"journal-article","created":{"date-parts":[[2012,11,12]],"date-time":"2012-11-12T07:34:30Z","timestamp":1352705670000},"page":"628-636","source":"Crossref","is-referenced-by-count":40,"title":["The relationship between intracellular and plasma levels of folate and metabolites in the methionine cycle: A model"],"prefix":"10.1002","volume":"57","author":[{"given":"Tanya M.","family":"Duncan","sequence":"first","affiliation":[{"name":"Department of Biology Duke University  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael. C.","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Mathematics Duke University  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Frederik","family":"Nijhout","sequence":"additional","affiliation":[{"name":"Department of Biology Duke University  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,11,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/153537020422901002"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2009.10.010"},{"issue":"9","key":"e_1_2_7_4_1","first-page":"825","article-title":"A polymorphism of the methionine synthase gene: association with plasma folate, vitamin B12, homocyst(e)ine, and colorectal cancer risk","volume":"8","author":"Ma J.","year":"1999","journal-title":"Cancer Epidemiology Biomarkers Prev."},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.49.1.31"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000522"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/80.6.1611"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/131.11.2811"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.19.1.217"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.325.7354.1"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4682-5-8"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-07-2937"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.2005.067371"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/136.1.153"},{"key":"e_1_2_7_15_1","first-page":"43","volume-title":"Folate in Health and Disease","author":"Lindenbaum J.","year":"1995"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1993.03510220049033"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1521-6616(03)00204-3"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/137.2.311"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002725200"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.22.120701.083554"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-4526(08)60021-2"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/65.1.53"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.200900167"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.1.2.2677"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410818200"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/136.1.189"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-152CO"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/87.3.517"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/128.11.1907"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709487104"},{"key":"e_1_2_7_31_1","first-page":"1","volume-title":"Folate in Health and Disease","author":"Shane B.","year":"1995"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0910079"},{"key":"e_1_2_7_33_1","first-page":"473","article-title":"Plasma homocysteine, a risk factor for vascular disease: plasma levels in health, disease, and drug therapy","volume":"114","author":"Ueland P.","year":"1989","journal-title":"J. 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