This document discusses asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase that is an important cause of endothelial dysfunction. It is a byproduct of protein methylation and is normally cleared from the body by dimethylarginine dimethylaminohydrolase (DDAH). However, increased levels of ADMA are associated with several cardiovascular risk factors like hypercholesterolemia, insulin resistance, chronic kidney disease, and hypertension. Higher ADMA concentrations also correlate with the presence of atherosclerosis and predict acute coronary events and mortality in critically ill patients. The document outlines the synthesis and clearance of ADMA and its interactions with oxidative stress and nitric oxide synthase.

1. ASYMMETRIC DIMETHYL ARGININE
(ADMA)
M.Prasad Naidu
MSc Medical Biochemistry,
Ph.D.Research Scholar

2. 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

3.  Basic semi-essential amino acid
 Glucogenic
 Sources : Exogenous sources –
- Plant sources
- Animal sources
- Endogenous sources

5.  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.

6. 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

7. Synthesis of ADMA

8. 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

9.  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

10. INTERACTIONS BETWEEN OXIDATIVE STRESS, DIMETHYL ARGININE,
DIMETHYL AMINO HYDROLASE (DDAH) AND A SYMMETRIC DIMETHYL
ARGININE (ADMA) AND NITRIC OXIDE SYNTHASE (NOS).

11. 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

12.  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.

13. 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

14.  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

15. 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.

18. METHODS FOR MEASUREMENT OF ADMA

19. Thank
you