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The NuGOwiki Metabolite Database is a joint initiative of NuGO and HMDB
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| Arginine | |
|---|---|
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| Chemical Name | 2-amino-5- (diaminomethylideneamino) pentanoic acid |
| Chemical Formula | C6H14N4O2 |
| CAS Number | 74-79-3 |
| Chemical Information | HMDB00517 |
| Biochemical Taxonomy | amino acid |
| Functional Taxonomy | antioxidant free radical growth hydrolysis oxidant |
| Nutritional Taxonomy | conditionally essential amino acid |
| Metabolic Pathways | Amino Acid Metabolism |
| Biofluid Location | urine, plasma |
| Tissue Location | |
| Normal Biofluid Concentrations | Urine: 0.6579-5.921 umol/mmol creatinine 0-18.95 umol/mmol creatinine 1.67 +/- 0.62 umol/mmol creatinine (n = 7, male adults) Plasma: 23.33 +/- 36.27 uM 60.6 +/- 18.3 umol/L (n=14, adults) CSF: 20.5 uM (range = 15.7-25.3 uM) |
| Normal Tissue Concentrations | 140 uM (range = 50-230 uM) - concentrations from Hexamita inflata (Protozoon) |
| Diseases / Conditions Related to Nutrition | atherosclerosis cancer hypertension |
| Other (Monogenic Disorders) | |
| Abnormal Biofluid Concentrations | Urine: 902.30 +/- 2,011.18 umol/mmol creatinine Argininosuccinic Aciduria (asl): decreased/normal Argininemia, Hyperargininemia, Arginase Deficiency: 65.79-98.68 umol/mmol creatinine Argininemia, Hyperargininemia, Arginase Deficiency: increased Delta-pyrrolidine-5-carboxylate Synthase Deficiency: decreased Hyperdibasic Aminoaciduria I: 1.316-6.579 umol/mmol creatinine Hyperdibasic Aminoaciduria II, Lysinuric Protein Intolerance: 1.316-6.579 umol/mmol creatinine Cystinuria: 200-800 umol/mmol creatinine Hyperornithinemia with Gyrate Atrophy (hoga): increased Plasma: Delta-prolidine-5-carboxylate Synthase Deficiency: decreased Argininemia, Hyperargininemia, Arginase Deficiency: 1000.00-1500.00 uM Argininemia, Hyperargininemia, Arginase Deficiency: increased Argininosuccinic Aciduria (asl): decreased/normal CSF: Argininemia, Hyperargininemia, Arginase Deficiency: increased Argininemia, Hyperargininemia, Arginase Deficiency: increased |
| Abnormal Tissue Concentrations | |
| Physiological Processes | |
| Authors: | |
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Contents |
Introduction
guidelines
L-Arginine is a semi-essential amino acid involved in numerous areas of human physiology, including production of nitric oxide (NO) – a key messenger molecule involved in vascular regulation, immune activity, and endocrine function. Arginine is also involved in protein production, wound healing, erectile function, and fertility.
Arginine is not considered essential because humans can synthesize it de novo from glutamine, glutamate, and proline, which are substrates for the synthesis of citrulline in the small intestine. Citrulline is then released into the blood circulation, where it is extracted primarily by the kidneys for conversion to arginine (intestinal-renal axis of arginine synthesis). Arginine is then released into the blood circulation (Wu G, 1998).
It must be mentioned, however, that dietary intake remains the primary determinant of plasma arginine levels, since the rate of arginine biosynthesis does not compensate for depletion or inadequate supply. Arginine is the most abundant nitrogen carrier in humans, containing four nitrogen atoms per molecule. Arginine is not a major inter-organ nitrogen shuttle; instead, it plays an important role in nitrogen metabolism and ammonia detoxification as an intermediate in the urea cycle.
Biological Function
guidelines
The main importance of arginine is attributed to its role as a precursor for the synthesis of nitric oxide (NO). NO has important functional roles in a variety of physiological systems. The vasculoprotective roles of NO include regulation of blood pressure and vascular tone, inhibition of platelet aggregation and leukocyte adhesion, and inhibition of proliferation of vascular smooth muscle cells (Napoli C, 2006). NO is involved in the regulation of apoptosis (Li CQ, 2005), and inflammation (Guzik TJ, 2003).
As arginine is also a precursor for other molecules, like creatine and polyamines, the biological functions of arginine are related with the functions of its metabolites. Polyamines, for example, are in multiple ways involved in cell growth and the maintenance of cell viability, so arginine is indirectly also involved in these processes.
Arginine plays an important role in the clearance of ammonia via arginase, the final enzyme of the hepatic urea cycle. This cycle is the major metabolic pathway by which waste nitrogen, generated mainly from protein and amino acid metabolism, is converted to urea that can excreted via urine.
Catabolism
guidelines
Arginine transport across the plasma membrane from various cells is the starting point in the catabolism of arginine, and can be regulated by various stimuli. For example, lipopolysaccharide increases arginine transport in intestinal epithelial cells (Meng Q, 2005), and tumour necrosis factor can induce uptake of arginine in liver cells (Pacitti AJ, 1992). Once inside the cell, arginine can be metabolised via several enzymes thereby producing essential molecules for proper cell function and cell growth.
1. First, arginine can be hydrolysed to urea (HMDB00294) and ornithine (HMDB00214) by arginase. There are two forms known of arginase, namely arginase I and arginase II, encoded by two distinct genes, and expressed in different tissues with a different subcellular localization (Jenkinson CP, 1996). Arginase I is a cytosolic enzyme which is primarily expressed in the periportal hepatocyte, and is thought to be mainly involved in the urea cycle. Minor expression is also observed in brains, small intestine and red blood cells of primates. Arginase II is a mitochondrial enzyme and is more widely expressed, with the highest expression in kidney and prostate (Vockley JG, 1996). This enzyme is thought to be involved in all other functions that arginase might have, like the biosynthesis of polyamines, glutamate and proline, and the modulation of NO synthesis (Cederbaum SD, 2004). Ornithine production, which coincides with arginase activity, can subsequently be used for polyamine synthesis by ornithine decarboxylase.
2. Another arginine-metabolising enzyme is NO synthase (NOS) which converts arginine to NO (HMDB03378) and citrulline (HMDB00904). Arginine is the only precursor for NO production, thus processes that regulate arginine availability can play an important role in regulating NO synthesis. Three isoforms of NOS are known, namely endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS). NO production is quite low compared to overall arginine catabolism, and this is probably due to its function, including signal transduction, cytotoxicity, vascular tone, and inflammation.
3. Arginine is also used for creatine synthesis via the enzyme arginine:glycine amidinotransferase, an enzyme predominantly present in the renal tubules and pancreas. The enzyme transfers the guanidino group from arginine to glycine, with the formation of guanidinoacetate and ornithine. The kidneys are the main site for guanidinoacetate formation, whereas methylation of this molecule occurs mainly in the liver and the pancreas, yielding creatine (HMDB00064) which is released in the blood circulation (Wu G, 1998).
4. Arginine decarboxylase activity, converting arginine to agmatine (HMDB01432) and CO2, has been identified in brain, liver, kidney. Agmatine is hydrolysed by the mitochondrial enzyme agmatinase with the formation of urea and putrescine (HMDB01414), and hence this is an alternate route of polyamine synthesis (Wu G, 1998).
5. Last but not least, arginine serves as a substrate for protein synthesis in the form of arginyl-tRNA.
Diseases / Conditions Related to Nutrition
guidelines
Septic patients show decreased plasma arginine levels compared with control hospital patient, hence sepsis might be regarded as an arginine deficiency state, in which supplementation with this amino acid may be required (Luiking YC, 2004).
Lower plasma arginine concentrations are also observed in cancer patients (Vissers YL, 2005). Preterm infants suffer also from hypoargininemia, probably by the limited citrulline and arginine synthesis owing to the limited gene expression of the key enzymes (Wu G, 2004).
NO is involved in the condition of the respiratory system (Ricciardolo FL, 2004), and the arginine-arginase balance plays a role in asthma and lung inflammation (Zimmermann N, 2006). Arginine plays a role in vascular pathology as a precursor for NO.
Associated decreased protein/metabolite profile
Associated increased protein/metabolite profile
Other (Monogenic) Disorders
guidelines
Liver arginase (arginase I) deficiency exists in humans, but it was shown that these patients exhibit a compensatory up-regulation of the arginase II activity in the kidney in response to elevated arginine levels in the serum (Spector EB, 1983). This results in a less severe clinical disorder (Crombez EA, 2005), as compared with other urea cycle disorders.
Arginine:glycine amidinotransferase deficiency results in defects in the creatine synthesis and phenotypic expression of the disease, being mental retardation and epilepsy, can be prevented effectively by creatine supplementation (Battini R, 2006).
Nutritional Information
guidelines
There are no established nutritional guidelines for daily arginine intake.
In a large-scale cross-sectional study in the United States, almost 50% of the participants had an average arginine intake of 2.5-5 g per day, and 20% had an intake of 5-7.5 g per day (Wells BJ, 2005). Arginine is found commonly in many foods. The most common sources of arginine in the United States diet are meat, poultry and fish, dairy products, and cereal (Visek WJ, 1986).
A study in an elderly population (about 70 years of age) in The Netherlands showed an average arginine intake of 4.4 g per day, of which meat contributed the most to the total arginine intake, followed by bread and milk products (Oomen CM, 2000).
Approximately 2.3 g of arginine per day is required to maintain creatine homeostasis in adult humans (Wu G, 1998).