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Journal of Parenteral and Enteral Nutrition
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*(L)-ARGININE
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*Liver Diseases
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The Prominent Role of the Liver in the Elimination of Asymmetric Dimethylarginine (ADMA) and the Consequences of Impaired Hepatic Function

Milan C. Richir, MD1,2, Roderick H. Bouwman1, Tom Teerlink, PhD3, Michiel P.C. Siroen, MD, PhD1, Theo P.G.M. de Vries, MD, PhD2 and Paul A.M. van Leeuwen, MD, PhD1

From the 1 Departments of Surgery,2 Clinical Pharmacology and Pharmacy, and3 Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.

Address correspondence to: Paul A.M. van Leeuwen, MD, PhD, VU University Medical Center, Department of Surgery, PO Box 7057, 1007 MB Amsterdam, The Netherlands; e-mail: pam.vleeuwen{at}vumc.nl.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS), the enzyme which converts the amino acid arginine into nitric oxide (NO). ADMA has been identified as an important risk factor for cardiovascular diseases. Besides the role of ADMA in cardiovascular diseases, it also seems to be an important determinant in the development of critical illness, (multiple) organ failure, and the hepatorenal syndrome. ADMA is eliminated from the body by urinary excretion, but it is mainly metabolized by the dimethylarginine dimethylaminohydrolase (DDAH) enzymes that convert ADMA into citrulline and dimethylamine. DDAH is highly expressed in the liver, which makes the liver a key organ in the regulation of the plasma ADMA concentration. The prominent role of the liver in the elimination of ADMA and the consequences of impaired hepatic function on ADMA levels will be discussed in this article.

Key Words: ADMA • arginine • DDAH • NO • liver

Journal of Parenteral and Enteral Nutrition, Vol. 32, No. 6, 613-621 (2008)
DOI: 10.1177/0148607108321702
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