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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1419.)
© 2006 American Heart Association, Inc.

Editorials

New Tricks From an Old Dog

Nitric Oxide-Independent Effects of Dimethylarginine Dimethylaminohydrolase

James Leiper; Patrick Vallance

From The British Heart Foundation Laboratories, Division of Medicine, University College London, UK.

Correspondence to James Leiper, The British Heart Foundation Laboratories, Division of Medicine, University College London, London, UK. E-mail james.leiper@ucl.ac.uk

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The enzyme dimethylarginine dimethylaminohydrolase (DDAH) metabolizes asymmetrically methylated arginine (namely L-N monomethylarginine [L-NMMA] and asymmetrical dimethylarginine [ADMA]) residues to citrulline and methylamine.¹ Considerable interest has been focused on the biology of DDAH after the discovery that asymmetrically methylated arginines (in particular ADMA) are competitive inhibitors of all 3 isoforms of nitric oxide synthase (NOS).² The observations that plasma ADMA levels are elevated in a range of cardiovascular disorders, some of which are associated with impaired NO generation, has led to the suggestion that inhibition of NOS activity by endogenously produced ADMA represents a novel mechanism to regulate NO production in vivo.^3,4 Furthermore, it has been suggested that DDAH activity might be required to maintain ADMA levels below the concentration at which NOS inhibition would occur or might act to fine tune NOS activity by maintaining tonic inhibition of NOS^3,4 (Figure).

View larger version (31K): [in this window] [in a new window]   The DDAH/ADMA pathway. Methylation of arginine residues (R) in proteins and subsequent proteolysis results in the liberation of free methylarginines, including asymmetrical dimethylarginine (ADMA), an inhibitor of nitric oxide synthases (NOS). ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) to citrulline (CIT) and dimethylamine (MA). ADMA is recognized as a plasma marker of increased cardiovascular risk, but it is unclear whether it ever accumulates to sufficient levels to affect NO pathways. DDAH might also exert biological effects through protein-protein interactions. DDAH1 has previously been shown to interact with neurofibromin 1 (NF1) and promote it’s phosphorylation (P). The physiological effect of this interaction remains to be determined (?). In . . . [Full Text of this Article]

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				F. Palm, M. L. Onozato, Z. Luo, and C. S. Wilcox Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3227 - H3245. [Abstract] [Full Text] [PDF]