In many pathological circumstances, asymmetric dimethylarginine is a sign of endothelial dysfunction and an endogenous activator of nitric oxide synthase (NOS). When HIV-1 is present, there is an increase in asymmetric dimethylarginine (ADMA) [1].

Metabolism / Metabolites
Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.

Toxicity Summary
Uremic toxins such as asymmetric dimethylarginine are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869).

[1]. The cardiovascular risk marker asymmetric dimethylarginine is elevated in asymptomatic, untreated HIV-1 infection and correlates with markers of immune activation and disease progression. Ann Clin Biochem. 2014 Sep;51(Pt 5):568-75.

N(omega),N(omega)-dimethyl-L-arginine is a L-arginine derivative having two methyl groups both attached to the primary amino moiety of the guanidino group. It has a role as an EC 1.14.13.39 (nitric oxide synthase) inhibitor. It is a non-proteinogenic L-alpha-amino acid, a member of guanidines, a L-arginine derivative and a dimethylarginine. It is a conjugate base of a N(omega),N(omega)-dimethyl-L-argininium(1+).
Asymmetric dimethylarginine (ADMA) is a naturally occurring chemical found in blood plasma. It is a metabolic by-product of continual protein modification processes in the cytoplasm of all human cells which is closely related to L-arginine, a conditionally-essential amino acid. ADMA interferes with L-arginine in the production of nitric oxide, a key chemical to endothelial and hence cardiovascular health.
N,N-dimethylarginine has been reported in Drosophila melanogaster, Schizosaccharomyces pombe, and other organisms with data available.
Asymmetric Dimethylarginine is a dimethylated derivative of L-arginine where the two methyl groups are attached to arginine in an asymmetrical configuration. Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of nitric oxide synthase (NOS) that is formed when S-adenosylmethionine protein N-methyltransferases transfer two methyl groups from S-adenosylmethionine to one of the two guanidine nitrogen groups of an arginine residue in a protein. ADMA is released when the protein is degraded and is a substrate for dimethylarginine dimethylaminohydrolase (DDAH). Free ADMA in plasma competes with the L-arginine for binding to the heme in NOS and inhibits nitric oxide (NO) synthesis. Decreased synthesis of NO inhibits vasodilation and leads to endothelial dysfunction. Elevated plasma levels of ADMA are seen in certain types of cancer, cardiovascular disease, hypertension, hyperlipidemia, type 2 diabetes mellitus, and increased oxidative stress.
Asymmetric dimethylarginine is a uremic toxin. Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and 3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.
Asymmetric dimethylarginine (ADMA) is a naturally occurring chemical found in blood plasma. It is a metabolic by-product of continual protein modification processes in the cytoplasm of all human cells. It is closely related to L-arginine, a conditionally-essential amino acid. ADMA interferes with L-arginine in the production of nitric oxide, a key chemical to endothelial and hence cardiovascular health. Asymmetric dimethylarginine is created in protein methylation, a common mechanism of post-translational protein modification. This reaction is catalyzed by an enzyme set called S-adenosylmethionine protein N-methyltransferases (protein methylases I and II). The methyl groups transferred to create ADMA are derived from the methyl group donor S-adenosylmethionine, an intermediate in the metabolism of homocysteine. (Homocysteine is an important blood chemical, because it is also a marker of cardiovascular disease). After synthesis, ADMA migrates into the extracellular space and thence into blood plasma. Asymmetric dimethylarginine is measured using high performance liquid chromatography.
Dimethyl-L-arginine is a metabolite found in or produced by Saccharomyces cerevisiae.

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Pharmacodynamics
Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is formed by methylation of arginine residues in proteins and released after proteolysis. In this reaction, S-adenosylmethionine is methyldonor and S-adenosylhomocysteine the demethylated product. ADMA and homocysteine are thus biochemically linked. Both plasma homocysteine and ADMA concentrations are increased in patients with renal dysfunction, probably as a result of an impairment in their metabolic, but not urinary, clearance. Hyperhomocysteinemia has been associated with an increased risk of cardiovascular disease in end-stage renal disease, especially in patients without malnutrition and inflammation. Also, plasma ADMA levels have been associated with cardiovascular disease in renal failure patients. Both homocysteine and ADMA are thought to mediate their adverse vascular effects by impairing endothelial, nitric oxide-dependent function resulting in decreased vasodilatation, increased smooth muscle cell proliferation, platelet dysfunction and increased monocyte adhesion.

C8H18N4O2

202.25412

202.143

30315-93-6

Asymmetric-dimethylarginine-d6 dihydrochloride;1313730-20-9;Asymmetric dimethylarginine dihydrochloride;220805-22-1;Asymmetric dimethylarginine-d7 hydrochloride hydrate

123831

White to off-white solid powder

1.239g/cm3

372.555°C at 760 mmHg

195 - 197 °C

179.115°C

0.455

3

4

6

14

215

1

CN(C)C(=NCCC[C@@H](C(=O)O)N)N

YDGMGEXADBMOMJ-LURJTMIESA-N

InChI=1S/C8H18N4O2/c1-12(2)8(10)11-5-3-4-6(9)7(13)14/h6H,3-5,9H2,1-2H3,(H2,10,11)(H,13,14)/t6-/m0/s1

(2S)-2-amino-5-[[amino(dimethylamino)methylidene]amino]pentanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~494.44 mM)
H2O : ~100 mg/mL (~494.44 mM)

Solubility in Formulation 1: 100 mg/mL (494.44 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)