ADMA-Arginine ELISA Kit

There are three types of methylated arginine in eukaryotes, including NG-monomethyl-L-arginine (L-NMMA), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). They are all formed by methylation modification of some intracellular arginine residue-containing proteins by protein arginine methyltransferase (PRMT). PRMT is divided into type I and type II, with the former mainly promoting the formation of ADMA and L-NMMA and the latter mainly generating SDMA and L-NMMA. ADMA is a nitric oxide synthase (NOS) inhibitor that inhibits nitric oxide (NO) production by competing with L-arginine for the active NOS binding site. ADMA has three metabolic pathways, dimethylarginine dimethylaminehydrolase (DDAH) hydrolysis, metabolism by alanine-glyoxylate aminotransferase (AGXT2) and renal excretion. Most of ADMA is specifically hydrolysed by DDAH to produce citrulline and dimethylamine, and the remainder is metabolised by AGXT2 hydrolysis and renal clearance. DDAH1 is predominantly distributed in tissues expressing neurogenic NOS, such as brain and kidney, whereas DDAH2 is predominantly distributed in tissues expressing endothelial NOS, such as blood vessels and heart.

Figure 1. Schema outlining the synthesis and metabolism of ADMA and SDMA
(Source: Tain YL, et al. 2017)

ADMA reduces mitochondrial biosynthesis and lowers mitochondrial membrane potential. Decrease in mitochondrial membrane potential is an early manifestation of apoptosis. Once the mitochondrial membrane potential decreases, it will lead to loss of coupling of the oxidative phosphorylation chain of the respiratory chain, swelling and rupture of the mitochondrial matrix, release of pro-apoptotic proteins, and the cell enters into an irreversible apoptotic process. A variety of cardiovascular risk factors have been found to induce a decrease in cellular mitochondrial membrane potential, leading to cell death. In addition, the researchers used cultured cardiomyocytes to demonstrate that ADMA can directly cause a decrease in cellular mitochondrial membrane potential, resulting in impaired mitochondrial function. ADMA promotes oxidative stress. Increased oxidative stress in diseases such as hyperlipidemia, atherosclerosis and diabetes mellitus is closely associated with elevated plasma ADMA.

ADMA is considered a new predictor of cardiovascular disease. Competitive inhibition of NOS by ADMA reduces NO levels and causes vascular endothelial dysfunction. Impaired vascular endothelial function can disrupt the balance between endothelial cell synthesis and secretion of vasodilatory and vasoconstrictive substances, inducing vascular equilibrium muscle proliferation and thrombus formation, thereby accelerating atherosclerosis and arterial plaque formation. Some researchers have found that injecting ADMA into mice for 4 weeks promotes the formation of coronary atherosclerotic plaques. In a clinical trial analysing patients with early-onset coronary artery disease, the investigators found that ADMA concentrations were significantly higher in the group of patients with coronary artery disease than in the control group, and that ADMA concentrations correlated with lesion severity.

Asymmetric dimethylarginine-Arginine