ADMA - Asymmetrical Dimethylarginine | Elisa - Clia - Antibody - Protein

Background

Asymmetrical dimethylarginine (ADMA) is an endogenous compound derived from the breakdown of proteins containing methylated arginine residues. ADMA is a methylated derivative of the amino acid arginine. It contains two methyl groups attached asymmetrically to one of the nitrogen atoms in the guanidino group of arginine. ADMA is primarily metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which converts ADMA into dimethylamine and L-citrulline. DDAH activity influences ADMA levels, and alterations in DDAH expression or activity can affect ADMA concentrations in the body. ADMA is considered an endogenous inhibitor of nitric oxide synthase (NOS), the enzyme responsible for synthesizing nitric oxide (NO) from arginine. Increased ADMA levels can impair NO production by competing with arginine for NOS binding, leading to endothelial dysfunction, impaired vasodilation, and increased vascular tone. Therefore, ADMA is implicated in the pathogenesis of various cardiovascular diseases, including hypertension, atherosclerosis, and endothelial dysfunction.Elevated ADMA levels have been associated with several cardiovascular risk factors and diseases, including hypertension, coronary artery disease, heart failure, stroke, and chronic kidney disease. ADMA levels are considered a biomarker for endothelial dysfunction and cardiovascular risk, and measuring ADMA concentrations may help assess disease severity and prognosis in certain conditions.

Protein Structure

ADMA itself is a modified amino acid rather than a protein, consisting of an L-arginine molecule with two methyl groups attached to one of its terminal nitrogen atoms. It is structurally characterized by:

• L-Arginine Core: The basic structure of arginine.
• Methyl Groups: Two methyl groups asymmetrically attached to one of the terminal nitrogen atoms (dimethylation).

Classification and Subtypes

ADMA belongs to a group of methylated arginine derivatives, which includes:

• Asymmetrical Dimethylarginine (ADMA)
• Symmetrical Dimethylarginine (SDMA): Does not inhibit NOS and is excreted in the urine.
• NG-Monomethyl-L-arginine (L-NMMA): Another NOS inhibitor but less potent than ADMA.

Function and Biological Significance

ADMA has several key roles in biological systems:

1. NOS Inhibition: ADMA competes with L-arginine for NOS, reducing NO production, which affects vasodilation and vascular tone.
2. Regulation of Vascular Function: By modulating NO levels, ADMA influences endothelial function, vascular resistance, and blood pressure.
3. Cellular Signaling: ADMA can modulate signaling pathways involved in cell growth, apoptosis, and inflammation through its effects on NO production.

Interactions

ADMA interacts with various molecules and pathways:

1. Nitric Oxide Synthase (NOS): ADMA inhibits NOS activity, reducing NO production.
2. Dimethylarginine Dimethylaminohydrolase (DDAH): This enzyme degrades ADMA into citrulline and dimethylamine, regulating its levels in the body.
3. Endothelial Function: ADMA affects endothelial cells by modulating NO availability, impacting vascular health.

Clinical Significance

1. Cardiovascular Diseases: Elevated ADMA levels are associated with endothelial dysfunction, hypertension, atherosclerosis, and coronary artery disease. ADMA is considered a biomarker for cardiovascular risk.
2. Chronic Kidney Disease: Impaired renal function leads to decreased clearance of ADMA, contributing to cardiovascular complications in patients with kidney disease.
3. Diabetes: Higher ADMA levels are observed in patients with diabetes, correlating with vascular complications.
4. Pulmonary Hypertension: ADMA contributes to the pathophysiology of pulmonary hypertension by reducing NO availability in pulmonary vessels.
5. Metabolic Syndrome: Elevated ADMA levels are linked to components of metabolic syndrome, including insulin resistance and dyslipidemia.

Summary

Asymmetrical Dimethylarginine (ADMA) is a naturally occurring inhibitor of nitric oxide synthase (NOS), playing a crucial role in regulating NO production and vascular function. Structurally, ADMA is a dimethylated form of L-arginine. It interacts with NOS to inhibit NO synthesis and is degraded by the enzyme DDAH. Clinically, elevated ADMA levels are associated with cardiovascular diseases, chronic kidney disease, diabetes, pulmonary hypertension, and metabolic syndrome. As a biomarker and potential therapeutic target, ADMA is significant in understanding and managing various health conditions related to endothelial dysfunction and vascular health.