ADMA

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Information about ADMA
Health & Medicine

Published on March 27, 2014

Author: mprasadnaidu

Source: slideshare.net

Description

ASYMMETRIC DIMETHYL ARGININE (ADMA)

ASYMMETRIC DIMETHYL ARGININE (ADMA) M.Prasad Naidu MSc 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 µmol 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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