ASYMMETRIC DIMETHYL ARGININE (ADMA)

M.Prasad NaiduMSc Medical Biochemistry,Ph.D.Research Scholar

INTRODUCTION

The endothelium play a crucial role in the regulation of

vascular tone and structure and its dysfunction is or integral

part of the processes leading to atherosclerosis

A symmetric dimethyl arginine (ADMA) is an endogenous

competitive inhibitor of nitric oxide synthase and an important

cause of endothelial dysfunction

Basic semi-essential amino acid Glucogenic Sources : Exogenous sources – - Plant sources - Animal

sources - Endogenous sources

ADMA SYNTHESIS

Is a metabolic by product of continual protein modification

process is a naturally occurring chemical found in blood

plasma

The guanidino nitrogen of arginine residuces cretin protein

are methylaled by a group of enzymes called protein arginine

methyl transferases (PRMTS) yielding mono and di-methyl

arginines.

PRMTS (Protein arginine methyl transferases)

Are two types

- Type 1 PRMTS

- Type 2 PRMTS

ADMA is the major product of type 1 PRMTS

Type1PRMTS: Found mainly in endothelial and smooth muscle

cells in cytoplasm of all human cells

Type2 PRMTS : Central Nervous System

Synthesis of ADMA

CLEARANCE OF ADMA

Humans generate approximately 300 mol of ADMA/day. A small amount of which (10%) is excreted unchanged into the

urine 90% is metabolized by the enzyme dimethyl arginine dimethyl

amino hydrolase (DDAH) to yield citrulline and

dimethlyamine.

DDAH

2 Distinct Isoforms:

DDAH-1

DDAH-2

DDAH-1: Found mainly in tissues expressing neuronal nitric

oxide synthase

Liver

Kidney cortex

Lung

DDAH-2: Found mainly in those tissue expressing-endothelial Nos (eNoS)

Inducible In endothelium and smooth muscle cells of cardio vascular

system Also highly expressed in the kidney

INTERACTIONS BETWEEN OXIDATIVE STRESS, DIMETHYL ARGININE,

DIMETHYL AMINO HYDROLASE (DDAH) AND A SYMMETRIC DIMETHYL

ARGININE (ADMA) AND NITRIC OXIDE SYNTHASE (NOS).

CLINICAL ASSOCIATIONS

ADMA is associated with cardiovascular risk factors

Hypercholesterolaemia

ADMA concentrations are increased approximately two fold in

diet induced Hypercholesterolaemia

LDL cholesterol >4.1mmol/L was associated with reduced No

synthesis

INSULIN

ADMA play role in insulin resistance and decreased NO availability

help to drive insulin resistance.

Hyper glycerin impairs DDAH activity in human cells

Plasma ADMA concentration is increased in patients with type 2

diabetes mellitus.

Chronic kidney Disease (CKD)

Is a risk factor for cardio vascular disease.

Plasma ADMA concentration increase patient with end-stage renal

failure (ESRF).

Hypertension

In essential hypertension, ADMA concentration is increased two fold

and is associated with reduced levels of urinary NO metabolites

ADMA and Cardio Vascular Disease

ADMA concentration is associated with the presence and extent of

atherosclerotic vascular disease.

Increased ADMA concentration can predict

-

-Acute coronary events

- Myocardial infarction

- Peripheral arterial disease

- Chronic heart failure

ADMA in critical illness

ADMA concentration independently predicts mortality in critically

ill patients in the intensive care unit (ICU)

ADMA contributes to the development of multiple organ failure in

critical illness.

METHODS FOR MEASUREMENT OF ADMA

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