Dimethylarginine dimethylaminohydrolase regulation

Carol Wadham, Arduino Aleksander Mangoni

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Asymmetric dimethylarginine (ADMA), an endogenous methylated form of the amino acid L-arginine, inhibits the activity of the enzyme endothelial nitric oxide synthase, with consequent reduced synthesis of nitric oxide. ADMA is metabolised to L-citrulline and dimethylamine by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). The modulation of DDAH activity and expression plays a pivotal role in regulating intracellular ADMA concentrations, with important effects on vascular homeostasis. For example, impairment in DDAH activity, resulting in elevated ADMA concentrations and reduced nitric oxide synthesis, can promote the onset and progression of atherosclerosis in experimental models. This review discusses the current role of ADMA and DDAH in vascular health and disease, the techniques used to assess DDAH activity and expression, and the results of recent studies on pharmacological and biological agents modulating DDAH activity and expression. Suggestions for future basic and clinical research directions are also discussed.
Original languageEnglish
Pages (from-to)303-319
Number of pages17
JournalExpert Opinion on Drug Metabolism and Toxicology
Volume5
Issue number3
DOIs
Publication statusPublished - 1 Mar 2009

Fingerprint

Nitric Oxide
Citrulline
Nitric Oxide Synthase Type III
Biological Factors
Enzymes
Vascular Diseases
Blood Vessels
Arginine
dimethylargininase
Atherosclerosis
Homeostasis
Theoretical Models
Modulation
N,N-dimethylarginine
Health
Pharmacology
Amino Acids
Research
dimethylamine
Direction compound

Keywords

  • Amidohydrolases
  • Animals
  • Arginine
  • Cardiovascular Agents
  • Cardiovascular Diseases
  • Disease Progression
  • Drug Delivery Systems
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Nitric Oxide
  • asymmetric dimethylarginine
  • atherosclerosis
  • dimethylarginine dimethylaminohydrolase
  • endothelium
  • nitric oxide

Cite this

Dimethylarginine dimethylaminohydrolase regulation. / Wadham, Carol; Mangoni, Arduino Aleksander.

In: Expert Opinion on Drug Metabolism and Toxicology, Vol. 5, No. 3, 01.03.2009, p. 303-319.

Research output: Contribution to journalArticle

Wadham, Carol ; Mangoni, Arduino Aleksander. / Dimethylarginine dimethylaminohydrolase regulation. In: Expert Opinion on Drug Metabolism and Toxicology. 2009 ; Vol. 5, No. 3. pp. 303-319.
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