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Asymmetric dimethylarginine, endothelial dysfunction and renal disease.

Aldámiz-Echevarría L, Andrade F - Int J Mol Sci (2012)

Bottom Line: Most ADMA is degraded by dimethylarginine dimethyaminohydrolase (DDAH), distributed widely throughout the body and regulates ADMA levels and, therefore, NO synthesis.In recent years, several studies have suggested that increased ADMA levels are a marker of atherosclerotic change, and can be used to assess cardiovascular risk, consistent with ADMA being predominantly absorbed by endothelial cells.These factors contribute to endothelial dysfunction, oxidative stress and the progression of renal damage, but there are treatments that may effectively reduce ADMA levels in patients with kidney disease.

View Article: PubMed Central - PubMed

Affiliation: Division of Metabolism, Cruces University Hospital, Barakaldo, Basque Country 48903, Spain; E-Mail: fernando.andradelodeiro@osakidetza.net.

ABSTRACT
l-Arginine (Arg) is oxidized to l-citrulline and nitric oxide (NO) by the action of endothelial nitric oxide synthase (NOS). In contrast, protein-incorporated Arg residues can be methylated with subsequent proteolysis giving rise to methylarginine compounds, such as asymmetric dimethylarginine (ADMA) that competes with Arg for binding to NOS. Most ADMA is degraded by dimethylarginine dimethyaminohydrolase (DDAH), distributed widely throughout the body and regulates ADMA levels and, therefore, NO synthesis. In recent years, several studies have suggested that increased ADMA levels are a marker of atherosclerotic change, and can be used to assess cardiovascular risk, consistent with ADMA being predominantly absorbed by endothelial cells. NO is an important messenger molecule involved in numerous biological processes, and its activity is essential to understand both pathogenic and therapeutic mechanisms in kidney disease and renal transplantation. NO production is reduced in renal patients because of their elevated ADMA levels with associated reduced DDAH activity. These factors contribute to endothelial dysfunction, oxidative stress and the progression of renal damage, but there are treatments that may effectively reduce ADMA levels in patients with kidney disease. Available data on ADMA levels in controls and renal patients, both in adults and children, also are summarized in this review.

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(a) Arginine-nitric oxide metabolic pathway. The abbreviations stand for the following compounds: nitric oxide synthase (NOS), asymmetric dimethylarginine (ADMA), nitric oxide (NO), protein arginine methyltransferase (PRMT) and dimethylarginine dimethylaminohydrolase (DDAH); (b) Molecular diagram illustrating the inhibitory role of asymmetric dimethylarginine (ADMA) on nitric oxide (NO) production.
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f2-ijms-13-11288: (a) Arginine-nitric oxide metabolic pathway. The abbreviations stand for the following compounds: nitric oxide synthase (NOS), asymmetric dimethylarginine (ADMA), nitric oxide (NO), protein arginine methyltransferase (PRMT) and dimethylarginine dimethylaminohydrolase (DDAH); (b) Molecular diagram illustrating the inhibitory role of asymmetric dimethylarginine (ADMA) on nitric oxide (NO) production.

Mentions: l-arginine (Arg) can be broken down by several metabolic pathways: apart from its transformation into guanidinoacetate and creatine, it can be oxidized to l-citrulline (Citr) and NO by endothelial NOS (its main substrate) (Figure 2a). In line with this, acute or chronic administration of Arg increases the production of endothelial nitric oxide and improves endothelial function, decreasing the risk of atherothrombosis [15].


Asymmetric dimethylarginine, endothelial dysfunction and renal disease.

Aldámiz-Echevarría L, Andrade F - Int J Mol Sci (2012)

(a) Arginine-nitric oxide metabolic pathway. The abbreviations stand for the following compounds: nitric oxide synthase (NOS), asymmetric dimethylarginine (ADMA), nitric oxide (NO), protein arginine methyltransferase (PRMT) and dimethylarginine dimethylaminohydrolase (DDAH); (b) Molecular diagram illustrating the inhibitory role of asymmetric dimethylarginine (ADMA) on nitric oxide (NO) production.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472745&req=5

f2-ijms-13-11288: (a) Arginine-nitric oxide metabolic pathway. The abbreviations stand for the following compounds: nitric oxide synthase (NOS), asymmetric dimethylarginine (ADMA), nitric oxide (NO), protein arginine methyltransferase (PRMT) and dimethylarginine dimethylaminohydrolase (DDAH); (b) Molecular diagram illustrating the inhibitory role of asymmetric dimethylarginine (ADMA) on nitric oxide (NO) production.
Mentions: l-arginine (Arg) can be broken down by several metabolic pathways: apart from its transformation into guanidinoacetate and creatine, it can be oxidized to l-citrulline (Citr) and NO by endothelial NOS (its main substrate) (Figure 2a). In line with this, acute or chronic administration of Arg increases the production of endothelial nitric oxide and improves endothelial function, decreasing the risk of atherothrombosis [15].

Bottom Line: Most ADMA is degraded by dimethylarginine dimethyaminohydrolase (DDAH), distributed widely throughout the body and regulates ADMA levels and, therefore, NO synthesis.In recent years, several studies have suggested that increased ADMA levels are a marker of atherosclerotic change, and can be used to assess cardiovascular risk, consistent with ADMA being predominantly absorbed by endothelial cells.These factors contribute to endothelial dysfunction, oxidative stress and the progression of renal damage, but there are treatments that may effectively reduce ADMA levels in patients with kidney disease.

View Article: PubMed Central - PubMed

Affiliation: Division of Metabolism, Cruces University Hospital, Barakaldo, Basque Country 48903, Spain; E-Mail: fernando.andradelodeiro@osakidetza.net.

ABSTRACT
l-Arginine (Arg) is oxidized to l-citrulline and nitric oxide (NO) by the action of endothelial nitric oxide synthase (NOS). In contrast, protein-incorporated Arg residues can be methylated with subsequent proteolysis giving rise to methylarginine compounds, such as asymmetric dimethylarginine (ADMA) that competes with Arg for binding to NOS. Most ADMA is degraded by dimethylarginine dimethyaminohydrolase (DDAH), distributed widely throughout the body and regulates ADMA levels and, therefore, NO synthesis. In recent years, several studies have suggested that increased ADMA levels are a marker of atherosclerotic change, and can be used to assess cardiovascular risk, consistent with ADMA being predominantly absorbed by endothelial cells. NO is an important messenger molecule involved in numerous biological processes, and its activity is essential to understand both pathogenic and therapeutic mechanisms in kidney disease and renal transplantation. NO production is reduced in renal patients because of their elevated ADMA levels with associated reduced DDAH activity. These factors contribute to endothelial dysfunction, oxidative stress and the progression of renal damage, but there are treatments that may effectively reduce ADMA levels in patients with kidney disease. Available data on ADMA levels in controls and renal patients, both in adults and children, also are summarized in this review.

Show MeSH
Related in: MedlinePlus