Urinary excretion of methylarginine in human disease

Carnegie, P. R.; Fellows, Florence C. I.; Symington, G.

doi:10.1016/0026-0495(77)90097-x

Cited by 39 publications

(21 citation statements)

References 20 publications

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“…Unfortunately, the potential role of the liver in the metabolism of dimethylarginines has been underexposed. Carnegie and coworkers 15 pointed out the potential role of the liver in the metabolism of ADMA by reporting an increased urinary excretion of ADMA in patients with liver disease. However, no precise data on the hepatic metabolism of ADMA can be derived from this study, because only urinary concentrations were measured.…”

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confidence: 99%

The human liver clears both asymmetric and symmetric dimethylarginine

et al. 2005

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Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) inhibit production of nitric oxide. The concentration of both dimethylarginines is regulated by urinary excretion, although ADMA, but not SDMA, is also subject to degradation by dimethylarginine dimethylaminohydrolase, which is highly expressed in the liver but also present in the kidney. The exact roles of the human liver and kidney in the metabolism of dimethylarginines are currently unknown. Therefore, we aimed to investigate renal and hepatic handling of ADMA and SDMA in detail in 24 patients undergoing hepatic surgery. To calculate net organ fluxes and fractional extraction (FE) rates, blood was collected from an arterial line, the portal vein, hepatic vein, and renal vein, and blood flow of the hepatic artery, portal vein, and renal vein was determined using Doppler ultrasound techniques. Results showed a significant net uptake ( . FE rates of ADMA for the liver and kidney were 5.0% (3.5%-7.4%) and 8.4% (1.3%-13.9%), respectively. For SDMA, hepatic and renal FE rates were 3.4% (2.1%-7.5%) and 12.5% (3.6%-16.2%), respectively. In conclusion, this study gives a detailed description of the hepatic and renal elimination of dimethylarginines and shows that the clearing of SDMA is not only confined to the kidney, but the human liver also takes up substantial amounts of SDMA from the portal and systemic circulation. (HEPATOLOGY 2005;41:559-565.)

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The human liver clears both asymmetric and symmetric dimethylarginine

et al. 2005

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“…Urinary excretion of methylated arginines in demethylating human diseases Multiple sclerosis is one of the demyelinating diseases in humans. Under the conditions, MBP is dissociated from the membrane, and MBPfragments formed by intracellular proteolysis (Whitaker and Heinemann, 1983;Bever and Whitaker, 1985) and free amino acids find their way into the body fluids (Kakimoto and Akazawa, 1970;Carnegie et al, 1977;Lou, 1979;Yudkoff et al, 1984). Furthermore, Park et al (1989) showed the presence of MBPspecific PM1 as well as its endogenous substrate in human cerebrospinal fluid.…”

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Biological methylation of myelin basic protein: Enzymology and biological significance

Kim

Lim

Park

et al. 1997

The International Journal of Biochemistry & Cell Biology

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“…In 1977, Car negie and co-workers [1] pointed out the potential role of the liver in the metabolism of asymmetric dimethylarginine (ADMA) by reporting an increased urinary excretion of ADMA in patients with liver disease. Later, it was shown in an organ balance study in rats that the liver takes up substantial amounts of ADMA, thereby suggesting a crucial role for the liver in regulating systemic ADMA concentrations [2] .…”

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confidence: 99%

Transjugular intrahepatic portosystemic shunt-placement increases arginine/asymmetric dimethylarginine ratio in cirrhotic patients

Siroen¹,

Wiest²,

Richir³

et al. 2008

WJG

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AIM:To analyze the change of dimethylarginine plasma levels in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt (TIPS). METHODS: To determine arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and nitric oxide (NO) plasma levels, blood samples were collected from the superior cava, hepatic, and portal vein just before, directly after, and 3 mo after TIPS-placement. RESULTS: A significant increase in the arginine/ADMA ratio after TIPS placement was shown. Moreover, TIPS placement enhanced renal function and thereby decreased systemic SDMA levels. In patients with renal dysfunction before TIPS placement, both the arginine/ ADMA ratio and creatinine clearance rate increased significantly, while this was not the case in patients with normal renal function before TIPS placement. Hepatic function did not change significantly after TIPS placement and no significant decline in ADMA plasma levels was measured. CONCLUSION:The increase of the arginine/ADMA ratio after TIPS placement suggests an increase in intracellular NO bioavailability. In addition, this study suggests that TIPS placement does not alter dimethylarginine dimethylaminohydrolase (DDAH) activity and confirms the major role of the liver as an ADMA clearing organ.

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Urinary excretion of methylarginine in human disease

Cited by 39 publications

References 20 publications

The human liver clears both asymmetric and symmetric dimethylarginine

The human liver clears both asymmetric and symmetric dimethylarginine

Biological methylation of myelin basic protein: Enzymology and biological significance

Transjugular intrahepatic portosystemic shunt-placement increases arginine/asymmetric dimethylarginine ratio in cirrhotic patients

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