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Role of L-Arginine in Nitric Oxide Synthesis and Health in Humans

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Amino Acids in Nutrition and Health

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1332))

Abstract

As a functional amino acid (AA), L-arginine (Arg) serves not only as a building block of protein but also as an essential substrate for the synthesis of nitric oxide (NO), creatine, polyamines, homoarginine, and agmatine in mammals (including humans). NO (a major vasodilator) increases blood flow to tissues. Arg and its metabolites play important roles in metabolism and physiology. Arg is required to maintain the urea cycle in the active state to detoxify ammonia. This AA also activates cellular mechanistic target of rapamycin (MTOR) and focal adhesion kinase cell signaling pathways in mammals, thereby stimulating protein synthesis, inhibiting autophagy and proteolysis, enhancing cell migration and wound healing, promoting spermatogenesis and sperm quality, improving conceptus survival and growth, and augmenting the production of milk proteins. Although Arg is formed de novo from glutamine/glutamate and proline in humans, these synthetic pathways do not provide sufficient Arg in infants or adults. Thus, humans and other animals do have dietary needs of Arg for optimal growth, development, lactation, and fertility. Much evidence shows that oral administration of Arg within the physiological range can confer health benefits to both men and women by increasing NO synthesis and thus blood flow in tissues (e.g., skeletal muscle and the corpora cavernosa of the penis). NO is a vasodilator, a neurotransmitter, a regulator of nutrient metabolism, and a killer of bacteria, fungi, parasites, and viruses [including coronaviruses, such as SARS-CoV and SARS-CoV-2 (the virus causing COVID-19). Thus, Arg supplementation can enhance immunity, anti-infectious, and anti-oxidative responses, fertility, wound healing, ammonia detoxification, nutrient digestion and absorption, lean tissue mass, and brown adipose tissue development; ameliorate metabolic syndromes (including dyslipidemia, obesity, diabetes, and hypertension); and treat individuals with erectile dysfunction, sickle cell disease, muscular dystrophy, and pre-eclampsia.

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Abbreviations

AA:

Amino acid

ADMA:

Asymmetric dimethylarginine

AMPK:

AMP-activated protein kinase

Arg:

L-arginine

BH4:

Tetrahydrobiopterin

BW:

Body weight

COVID-19:

Coronavirus disease-2019

eNOS:

Endothelial nitric oxide synthase

GTP-CH1:

GTP cyclohydrolase-I

NHANES:

National health and nutrition examination survey

iNOS:

Inducible nitric oxide synthase

NMMA:

NG-monomethylarginine

MTOR:

Mechanistic target of rapamycin

nNOS:

Neuronal nitric oxide synthase

NO:

Nitric oxide

PPAR:

Peroxisome proliferator-activated receptor

SARS-CoV:

Severe acute respiratory syndrome coronavirus

SARS-CoV-2:

Severe acute respiratory syndrome coronavirus 2

SCD:

Sickle cell disease

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Acknowledgements

We thank International Council of Amino Acid Science (Brussels, Belgium) for the financial support of our research on arginine safety and metabolism in adult humans.

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Authors and Affiliations

  1. Departments of Animal Science, Texas A&M University, College Station, Texas, 77843, USA

    Guoyao Wu & Fuller W. Bazer

  2. Medical Physiology, Texas A&M University, College Station, Texas, 77843, USA

    Guoyao Wu & Cynthia J. Meininger

  3. Faculty of Nutrition, Texas A&M University, College Station, Texas, 77843, USA

    Guoyao Wu

  4. Department of Internal Medicine, Baylor Scott & White Health, Temple, Texas, TX, 76508, USA

    Catherine J. McNeal

  5. Department of Pediatrics and Division of Gastroenterology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA

    J. Marc Rhoads

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  1. Guoyao Wu
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  4. Fuller W. Bazer
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Correspondence to Guoyao Wu .

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  1. Texas A&M Univesity, College Station, TX, USA

    Guoyao Wu

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Wu, G., Meininger, C.J., McNeal, C.J., Bazer, F.W., Rhoads, J.M. (2021). Role of L-Arginine in Nitric Oxide Synthesis and Health in Humans. In: Wu, G. (eds) Amino Acids in Nutrition and Health. Advances in Experimental Medicine and Biology, vol 1332. Springer, Cham. https://doi.org/10.1007/978-3-030-74180-8_10

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