ADMA

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ASYMMETRIC DIMETHYL ARGININE (ADMA)
M.Prasad Naidu MSc Medical Biochemistry, Ph.D.Rese
arch Scholar
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• 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

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Arginine

• Basic semi-essential amino acid
• Glucogenic
• Sources Exogenous sources
• 
  - Plant sources
• 
  - Animal sources
• - Endogenous sources

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Endogenous source of Arginine Urea Cycle
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• 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.

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• 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

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Synthesis of ADMA
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• 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

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• 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

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INTERACTIONS BETWEEN OXIDATIVE STRESS, DIMETHYL
ARGININE, DIMETHYL AMINO HYDROLASE (DDAH) AND A
SYMMETRIC DIMETHYL ARGININE (ADMA) AND NITRIC
OXIDE SYNTHASE (NOS).
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• CLINICAL ASSOCIATIONS
• ADMA is associated with cardiovascular risk
  factors
• Hypercholesterolaemia
• ADMA concentrations are increased approximately
  two fold in diet induced Hypercholesterolaemia
• LDL cholesterol gt4.1mmol/L was associated with
  reduced No synthesis

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• 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.

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• 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

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• 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
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  - Peripheral arterial disease
  - Chronic heart failure

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• 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.

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Evidence from prospective studies showing ADMA as
prognostic marker
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METHODS FOR MEASUREMENT OF ADMA
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• Thank you