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In this study, we compared the role of the plant urea cycle and its relationships to polyamine metabolism in ammonium-fed and nitrate-fed Medicago truncatula plants. High ammonium resulted in the accumulation of ammonium and pathway intermediates, particularly glutamine, arginine, ornithine, and putrescine. Arginine decarboxylase activity was decreased in roots, suggesting that the ornithine decarboxylase-dependent production of putrescine was important in situations of ammonium stress. The activity of copper amine oxidase, which releases ammonium from putrescine, was significantly decreased in both shoots and roots. In addition, physiological concentrations of ammonium inhibited copper amine oxidase activity in in vitro assays, supporting the conclusion that high ammonium accumulation favors putrescine synthesis. Moreover, early supplementation of plants with putrescine avoided ammonium toxicity. The levels of transcripts encoding urea-cycle-related proteins were increased and transcripts involved in polyamine catabolism were decreased under high ammonium concentrations. We conclude that the urea cycle and associated polyamine metabolism function as important protective mechanisms limiting ammonium toxicity in M. truncatula. These findings demonstrate the relevance of the urea cycle to polyamine metabolism in higher plants.<\/jats:p>","DOI":"10.1093\/jxb\/erac235","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T11:29:24Z","timestamp":1653391764000},"page":"5581-5595","source":"Crossref","is-referenced-by-count":33,"title":["The importance of the urea cycle and its relationships to polyamine metabolism during ammonium stress in\n                    <i>Medicago truncatula<\/i>"],"prefix":"10.1093","volume":"73","author":[{"given":"Marina","family":"Urra","sequence":"first","affiliation":[{"name":"Institute for Multidisciplinary Research in Applied Biology (IMAB), Department of Sciences, Public University of Navarre (UPNA) , Avda. de Pamplona 123, 31192 Mutilva , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Buezo","sequence":"additional","affiliation":[{"name":"Institute for Multidisciplinary Research in Applied Biology (IMAB), Department of Sciences, Public University of Navarre (UPNA) , Avda. de Pamplona 123, 31192 Mutilva , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Royo","sequence":"additional","affiliation":[{"name":"Institute for Multidisciplinary Research in Applied Biology (IMAB), Department of Sciences, Public University of Navarre (UPNA) , Avda. de Pamplona 123, 31192 Mutilva , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Cornejo","sequence":"additional","affiliation":[{"name":"Institute for Advanced Materials and Mathematics (INAMAT2), Department of Sciences, Public University of Navarre (UPNA) , Campus de Arrosad\u00eda, 31006 Pamplona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"L\u00f3pez-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Institute for Multidisciplinary Research in Applied Biology (IMAB), Department of Sciences, Public University of Navarre (UPNA) , Avda. de Pamplona 123, 31192 Mutilva , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Cerd\u00e1n","sequence":"additional","affiliation":[{"name":"Institute for Multidisciplinary Research in Applied Biology (IMAB), Department of Sciences, Public University of Navarre (UPNA) , Avda. de Pamplona 123, 31192 Mutilva , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Esteban","sequence":"additional","affiliation":[{"name":"Department of Plant Biology and Ecology, University of the Basque Country (UPV\/EHU) , Sarriena s\/n, Apdo. 644, 48080 Bilbao , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Mart\u00ednez-Merino","sequence":"additional","affiliation":[{"name":"Institute for Advanced Materials and Mathematics (INAMAT2), Department of Sciences, Public University of Navarre (UPNA) , Campus de Arrosad\u00eda, 31006 Pamplona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Gogorcena","sequence":"additional","affiliation":[{"name":"Department of Pomology, Aula Dei Experimental Station, Consejo Superior de Investigaciones Cient\u00edficas (CSIC) , Avda. de Monta\u00f1ana 1005, 50059 Zaragoza , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paraskevi","family":"Tavladoraki","sequence":"additional","affiliation":[{"name":"Department of Science, University Roma Tre , 00146 Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6621-6961","authenticated-orcid":false,"given":"Jose Fernando","family":"Moran","sequence":"additional","affiliation":[{"name":"Institute for Multidisciplinary Research in Applied Biology (IMAB), Department of Sciences, Public University of Navarre (UPNA) , Avda. de Pamplona 123, 31192 Mutilva , 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