Arginine metabolism and nutrition in growth, health and disease
Open accessAbstract
L-Arginine (Arg) is synthesised from glutamine, glutamate, and proline via the intestinal-renal axis in humans and most other mammals (including pigs, sheep and rats). Arg degradation occurs via multiple pathways that are initiated by arginase, nitric-oxide synthase, Arg:glycine amidinotransferase, and Arg decarboxylase. These pathways produce nitric oxide, polyamines, proline, glutamate, creatine, and agmatine with each having enormous biological importance. Arg is also required for the detoxification of ammonia, which is an extremely toxic substance for the central nervous system. There is compelling evidence that Arg regulates interorgan metabolism of energy substrates and the function of multiple organs. The results of both experimental and clinical studies indicate that Arg is a nutritionally essential amino acid (AA) for spermatogenesis, embryonic survival, fetal and neonatal growth, as well as maintenance of vascular tone and hemodynamics. Moreover, a growing body of evidence clearly indicates that dietary supplementation or intravenous administration of Arg is beneficial in improving reproductive, cardiovascular, pulmonary, renal, gastrointestinal, liver and immune functions, as well as facilitating wound healing, enhancing insulin sensitivity, and maintaining tissue integrity. Additionally, Arg or L-citrulline may provide novel and effective therapies for obesity, diabetes, and the metabolic syndrome. The effect of Arg in treating many developmental and health problems is unique among AAs, and offers great promise for improved health and wellbeing of humans and animals.
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In the cardiovascular system, increased free iron and/or copper can be related to aging or hemolytic disease.
“In the cardiovascular system, this can be related to aging (122) or hemolytic disease (1026).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [1026]
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Activities of arginase I and II are limiting for endothelial cell proliferation
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Self-citationReduced l-arginine Level and Decreased Placental eNOS Activity in Preeclampsia
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Developmental Changes in Polyamine Levels and Synthesis in the Ovine Conceptus1
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Self-citationde Jonge, W. J., Kwikkers, K. L., Velde, A. A. T., van Deventer, S. J. H., Nolte, M. A., Mebius, R. E., Ruijter, J. M., Lamers, M. C., & Lamers, W. H. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0216143 · Cited by 103 · see citing works
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Arginine and ornithine kinetics in severely burned patients: increased rate of arginine disposal
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Arginase I: a limiting factor for nitric oxide and polyamine synthesis by activated macrophages?
Kepka‐Lenhart, D., Mistry, S. K., Wu, G., & Morris, S. M. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.279.6.r2237 · Cited by 99 · see citing works
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l ‐Arginine treatment for asymmetric fetal growth restriction
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Arginine degradation in developing porcine enterocytes
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Self-citationArginine catabolism in lactating porcine mammary tissue2
O'Quinn, P. R., Knabe, D. A., & Wu, G. (2002) · Journal of Animal Science · doi:10.2527/2002.802467x · Cited by 87 · see citing works
Self-citationEffects of low‐dose <scp>l</scp>‐arginine on insulin‐mediated vasodilatation and insulin sensitivity
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“Similar results have been reported for obese humans with type-II diabetes receiving oral (Lucotti et al. 2006) or intravenous (Wascher et al. 1997) administration of Arg.”
ResultUnusual Abundance of Arginine and Ornithine in Porcine Allantoic Fluid1
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Regulation of L-arginine synthesis from L-citrulline by L-glutamine in endothelial cells
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Self-citationGlucocorticoid regulation of amino acid and polyamine metabolism in the small intestine
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Transport of amino acids through the placenta and their role
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Regulation of apoptosis by protein S-nitrosylation
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Self-citationL-Arginine Supplementation in Patients with Gestational Hypertension: A Pilot Study
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Dietary l-arginine prevents fetal growth restriction in rats
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Decreased systemic bioavailability of L-arginine in patients with cystic fibrosis
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A cortisol surge mediates the enhanced polyamine synthesis in porcine enterocytes during weaning
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Effect of L-Arginine Infusion on Infants with Persistent Pulmonary Hypertension of the Newborn
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Liver I/R injury is improved by the arginase inhibitor, Nω-hydroxy-nor- l -arginine (nor-NOHA)
Reid, K. M., Tsung, A., Kaizu, T., Jeyabalan, G., Ikeda, A., Shao, L., Wu, G., Murase, N., & Geller, D. A. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00227.2006 · Cited by 57 · see citing works
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Functional genomics and SNP analysis of human genes encoding proline metabolic enzymes
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Arginase blockade protects against hepatic damage in warm ischemia-reperfusion
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Self-citationKidney growth, hypertrophy and the unifying mechanism of diabetic complications
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Nitric oxide extends the oocyte temporal window for optimal fertilization
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Objective evidence of endothelial dysfunction in preeclampsia
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Lactate inhibits citrulline and arginine synthesis from proline in pig enterocytes
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Intestinal ribosomal p70 S6K signaling is increased in piglet rotavirus enteritis
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Self-citationEffects of NO synthase inhibitors, arginine-deficient diet, and amiloride in pregnant rats
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Healing of diabetic foot ulcers in l-arginine-treated patients
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Enhanced metabolism of arginine and glutamine in enterocytes of cortisol-treated pigs
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Self-citationThe effect of l ‐arginine administration on muscle force and power in postmenopausal women
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Polyamine synthesis inhibition induces S phase cell cycle arrest in vascular smooth muscle cells
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Self-citationThe Arginine Requirement of the Infant
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Self-citationL-Arginine infusion reduces preterm uterine contractions
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Níveis plasmáticos de vitamina A em crianças carentes com pneumonia na fase aguda e após recuperação
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Inhibition of nitric oxide synthesis causes preterm delivery in the mouse
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The Effects ofl-Arginine on Crypt Cell Hyperproliferation in Colorectal Cancer
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Studies on arginine in human semen
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Self-citationArginine and fetal growth in ovine models of intrauterine growth restriction
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Amino acids: Metabolism, functions, and nutrition
Wu, G. (2009) · Amino Acids · doi:10.1007/s00726-009-0269-0 · Cited by 3,004 · see citing works
Self-citationNitric oxide synthase in innate and adaptive immunity: an update
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Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
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Morris, S. M. (2016) · The Journal of Nutrition · doi:10.3945/jn.115.226621 · Cited by 435 · see citing works
McKnight, J. R., Satterfield, M. C., Jobgen, W. S., Smith, S. B., Spencer, T. E., Meininger, C. J., McNeal, C. J., & Wu, G. (2010) · Amino Acids · doi:10.1007/s00726-010-0598-z · Cited by 376 · see citing works
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Self-citationUtilization of amino acids by bacteria from the pig small intestine
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Self-citationIntestinal nitrogen recycling and utilization in health and disease
Bergen, W. G., & Wu, G. (2009) · The Journal of Nutrition · doi:10.3945/jn.109.104497 · Cited by 183 · see citing works
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Safety of dietary supplementation with arginine in adult humans
McNeal, C. J., Meininger, C. J., Wilborn, C. D., Tekwe, C. D., & Wu, G. (2018) · Amino Acids · doi:10.1007/s00726-018-2594-7 · Cited by 72 · see citing works
Self-citation“Nutraceuticals” in relation to human skeletal muscle and exercise
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NRF3 activates mTORC1 arginine-dependently for cancer cell viability
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- Authors
- Wu, G., Bazer, F. W., Davis, T. A., Kim, S. W., Li, P., Marc Rhoads, J., Carey Satterfield, M., Smith, S. B., Spencer, T. E., & Yin, Y.
- Affiliations
- Chinese Academy of Sciences (CN)
- Texas A&M University (US)
- Baylor College of Medicine (US)
- North Carolina State University (US)
- Corresponding author
- Wu, Guoyao
- ORCID
- Venue
- Amino Acids
- Published
- 2008-11-23
- Volume
- 37
- Issue
- 1
- Pages
- 153-168
- ISSN
- 0939-4451 (ISSN-L)
- 1438-2199
- PMC
- PMC2677116
- OpenAlex
- W2087285715
- Cited by
- 1,362
- References
- 177
- Citations by year
- 2026: 69 · 2025: 114 · 2024: 127 · 2023: 66 · 2022: 101 · 2021: 95 · 2020: 101 · 2019: 82 · 2018: 70 · 2017: 59 · 2016: 75 · 2015: 80 · 2014: 57 · 2013: 64 · 2012: 61
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Amino Acids (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- National Institutes of Health (5r21hd049449-02)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR044474)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21 HD049449, 1R21 HD049449)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- arginine metabolism, L-arginine, essential amino acids, nitric oxide, polyamines, agmatine, creatine, ammonia detoxification, spermatogenesis, embryonic development, vascular tone, dietary supplementation, citrulline, obesity, diabetes mellitus, metabolic syndrome, wound healing, insulin sensitivity, immune function, reproductive function
- MeSH terms
- Animals, Arginine, Cystic Fibrosis, Humans, Neoplasms, Nutritional Requirements, Obesity, Reproduction, Wounds and Injuries, Muscle, Skeletal, Metabolic Syndrome, Fetal Development
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