ArticleNature medicine2011
Requirement of argininosuccinate lyase for systemic nitric oxide production.
Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03064048 (Effect of Nitric Oxide), which is not on this map. Cited by 124 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Nitric Oxide (NO) Supplementation on Neurocognitive Measures in Argininosuccinate Lyase Deficiency (ASLD)
Who cites it
124 citing papers in PubMed, 1 synthesis or guideline pooled it, 223 citations in OpenAlex.
- The Association Between Concentrations of Arginine, Ornithine, Citrulline and Major Depressive Disorder: A Meta-Analysis.Frontiers in psychiatry · 2021Pooled it
- Trial
- Biomarkers for liver disease in urea cycle disorders.Molecular genetics and metabolism · 2021Trial
- Nitric oxide modulates bone anabolism through regulation of osteoblast glycolysis and differentiation.The Journal of clinical investigation · 2021Trial
- Argininosuccinate Lyase Deficiency Causes an Endothelial-Dependent Form of Hypertension.American journal of human genetics · 2018Trial
- Low plasma citrulline levels are associated with acute respiratory distress syndrome in patients with severe sepsis.Critical care (London, England) · 2013Trial
- A randomized controlled trial to evaluate the effects of high-dose versus low-dose of arginine therapy on hepatic function tests in argininosuccinic aciduria.Molecular genetics and metabolism · 2012Trial
- Article
- Serum Argininosuccinic Acid Is Associated with Diabetes in Patients with Coronary Artery Disease: An Exploratory Targeted LC-MS/MS Study.International journal of molecular sciences · 2026Article
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Sarcopenia in Pediatric Intoxication Type Inborn Errors of Metabolism: A Frequent and Underrecognized Condition.Journal of inherited metabolic disease · 2026Article
- L-Citrulline: Novel Pharmacotherapy to Improve Outcomes in Infants and Children at Risk of Systemic or Pulmonary Vascular Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Nitrogen Isotope Effects in Urea Metabolism: From Biochemistry toInternational journal of molecular sciences · 2026Review
- Impact of long-term nitrogen scavenger therapy on clinical outcome in individuals with urea cycle disorders.Scientific reports · 2026Article
- Predicting epistasis across proteins by structural logic.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The role of abnormal amino acid metabolism in the occurrence and development of tumors.Frontiers in oncology · 2026Review
- Arginine amino acid, nano particles of zinc oxide, and stock density: Effect on growth performance, intestinal morphology, blood indices, and meat quality in broiler chickens.Poultry science · 2026Article
- Current Treatment Modalities for Urea Cycle Disorders.Paediatric drugs · 2025Review
- Clinical, biochemical and genetic characteristics of patients with argininosuccinate lyase deficiency from a single center cohort in China.Orphanet journal of rare diseases · 2025Article
- Prevalence of fibrosis in hepatic explants and biopsies from individuals with urea cycle disorders.Molecular genetics and metabolism · 2025Article
64 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 10 institutions in 1 country.
Funding
Abstract
Nitric oxide (NO) is crucial in diverse physiological and pathological processes. We show that a hypomorphic mouse model of argininosuccinate lyase (encoded by Asl) deficiency has a distinct phenotype of multiorgan dysfunction and NO deficiency. Loss of Asl in both humans and mice leads to reduced NO synthesis, owing to both decreased endogenous arginine synthesis and an impaired ability to use extracellular arginine for NO production. Administration of nitrite, which can be converted into NO in vivo, rescued the manifestations of NO deficiency in hypomorphic Asl mice, and a nitric oxide synthase (NOS)-independent NO donor restored NO-dependent vascular reactivity in humans with ASL deficiency. Mechanistic studies showed that ASL has a structural function in addition to its catalytic activity, by which it contributes to the formation of a multiprotein complex required for NO production. Our data demonstrate a previously unappreciated role for ASL in NOS function and NO homeostasis. Hence, ASL may serve as a target for manipulating NO production in experimental models, as well as for the treatment of NO-related diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.