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Urea cycle disorders (UCDs) are inborn errors of metabolism causing impaired ureagenesis, leading to neurotoxic accumulation of ammonia and brain glutamine. Treatment includes dietary protein restriction and oral \u201cammonia scavengers.\u201d These scavengers chemically combine with glutamine and glycine to yield excretable products, creating an alternate pathway of waste nitrogen disposal. The amino acid transporter SLC6A19 is responsible for &gt;95% of absorption and reabsorption of free neutral amino acids in the small intestine and kidney, respectively. Genetic SLC6A19 deficiency causes massive neutral aminoaciduria but is typically benign. We hypothesized that inhibiting SLC6A19 would open a novel and effective alternate pathway of waste nitrogen disposal. To test this, we crossed SLC6A19 knockout (KO) mice with <jats:italic>spf<\/jats:italic><jats:sup><jats:italic>ash<\/jats:italic><\/jats:sup> mice, a model of ornithine transcarbamylase (OTC) deficiency. Loss of SLC6A19 in <jats:italic>spf<\/jats:italic><jats:sup><jats:italic>ash<\/jats:italic><\/jats:sup> mice normalized plasma ammonia and brain glutamine and increased median survival in response to a high protein diet from 7 to 97\u2009days. While induced excretion of amino acid nitrogen is likely the primary therapeutic mechanism, reduced intestinal absorption of dietary free amino acids, and decreased muscle protein turnover due to loss of SLC6A19 may also play a role. In summary, the results suggest that SLC6A19 inhibition represents a promising approach to treating UCDs and related aminoacidopathies.<\/jats:p>","DOI":"10.1002\/jimd.12568","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T02:24:08Z","timestamp":1665541448000},"page":"55-65","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Excretion of excess nitrogen and increased survival by loss of <scp>SLC6A19<\/scp> in a mouse model of ornithine transcarbamylase deficiency"],"prefix":"10.1002","volume":"46","author":[{"given":"Adam J.","family":"Belanger","sequence":"first","affiliation":[{"name":"Rare &amp; Neurologic Diseases Sanofi  Cambridge USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Gefteas","sequence":"additional","affiliation":[{"name":"Rare &amp; Neurologic Diseases Sanofi  Cambridge 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