{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:14:46Z","timestamp":1792649686366,"version":"4.5.0"},"reference-count":24,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:p> The stable isotopes of phenylalanine (Phe) and tyrosine (Tyr) are often used to study whole body protein metabolism in humans. Noncompartmental approaches give limited physiological insight in the compartmental characteristics. We therefore developed a compartmental mathematical model of Phe\/Tyr metabolism to describe protein fluxes by using stable tracer dynamic data in plasma following intravenous bolus of l-[ring-<jats:sup>13<\/jats:sup>C<jats:sub>6<\/jats:sub>]Phe and l-[ ring-<jats:sup>2<\/jats:sup>H<jats:sub>4<\/jats:sub>]Tyr in healthy subjects. The model consists of four compartments describing Phe\/Tyr kinetics. Because the model is a priori nonidentifiable, it is quantified in terms of two uniquely identifiable submodels representing two limit case scenarios, based on known physiology. The two submodels, identified by using the software SAAM II, fit well the experimental data of all individuals and provide an unbiased overview of the metabolic pathway in terms of intervals of validity of the non-uniquely identifiable variables. The model provides estimates of the flux from Phe to Tyr [4.1\u2009\u00b1\u20091.0 \u00b5mol\u00b7kg fat-free mass (FFM)<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup> (mean\u2009\u00b1\u2009SE)] and intervals of validity of the flux and pool estimates. Our preferred submodel yielded protein breakdown flux (50.5\u2009\u00b1\u20095.2 \u00b5mol\u00b7kg FFM<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup>), net protein breakdown (4.1\u2009\u00b1\u20091.0 \u00b5mol\u00b7kg FFM<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup>), Tyr from Phe hydroxylation (~12%), hydroxylated Phe (~8%), and flux ratio of Tyr to Phe arising from protein catabolism (0.68), consistent with available literature. The other submodel suggest that the assumptions made by noncompartmental analysis are consistently underestimated. Our accurate and detailed model for estimating Phe\/Tyr metabolic pathways in humans might be essential to applications in a variety of scenarios describing whole body protein synthesis and breakdown in health and disease. <\/jats:p>","DOI":"10.1152\/ajpendo.00362.2016","type":"journal-article","created":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T21:10:34Z","timestamp":1488921034000},"page":"E63-E74","source":"Crossref","is-referenced-by-count":29,"title":["A four-compartment compartmental model to assess net whole body protein breakdown using a pulse of phenylalanine and tyrosine stable isotopes in humans"],"prefix":"10.1152","volume":"313","author":[{"given":"Alvise","family":"Mason","sequence":"first","affiliation":[{"name":"Center for Translational Research in Aging &amp; Longevity, Department of Health and Kinesiology, Texas A&amp;M University, College Station, Texas;"},{"name":"Department of Information Engineering, Universita\u2019 degli Studi di Padova, Padua, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u00eblle P. K. J.","family":"Engelen","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Aging &amp; Longevity, Department of Health and Kinesiology, Texas A&amp;M University, College Station, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology, Texas A&amp;M University, College Station, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianna M.","family":"Toffolo","sequence":"additional","affiliation":[{"name":"Department of Information Engineering, Universita\u2019 degli Studi di Padova, Padua, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5845-6447","authenticated-orcid":false,"given":"Nicolaas E. P.","family":"Deutz","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Aging &amp; Longevity, Department of Health and Kinesiology, Texas A&amp;M University, College Station, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(81)90074-3"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(98)90064-6"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2007.07.002"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/dmr.5610050203"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1177\/0148607192016004305"},{"key":"B6","volume-title":"The Mathematical Modeling of Metabolic and Endocrine Systems: Model Formulation, Identification, and Validation","author":"Carson ER","year":"1983"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(82)90142-1"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1980.239.1.R7"},{"key":"B9","volume-title":"Tracer Kinetics in Biomedical Research: From Data to Model","author":"Cobelli C","year":"2000"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1991.261.4.E539"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/56.3.517"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(72)90442-1"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv271"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-08-034929-9.50005-4"},{"key":"B15","first-page":"525","volume":"50","author":"James WP","year":"1976","journal-title":"Clin Sci Mol Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1987.253.2.E173"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1042\/CS20140343"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/137.6.1549S"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1042\/bj2100811"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/B978-1-4832-3211-9.50016-4"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1995.269.1.E193"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1118\/1.3395579"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1989.256.5.E631"},{"key":"B24","volume-title":"Isotope Tracers in Metabolic Research: Principles and Practice of Kinetic Analysis","author":"Wolfe RR","year":"2005","edition":"2"}],"container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpendo.00362.2016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T01:48:59Z","timestamp":1567993739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpendo.00362.2016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,1]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,7,1]]}},"alternative-id":["10.1152\/ajpendo.00362.2016"],"URL":"https:\/\/doi.org\/10.1152\/ajpendo.00362.2016","relation":{},"ISSN":["0193-1849","1522-1555"],"issn-type":[{"value":"0193-1849","type":"print"},{"value":"1522-1555","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,1]]}}}