Accurate quantification of dimethylamine (DMA) in human urine by gas chromatography–mass spectrometry as pentafluorobenzamide derivative: Evaluation of the relationship between DMA and its precursor asymmetric dimethylarginine (ADMA) in health and disease

Plasma homoarginine, arginine, asymmetric dimethylarginine and total homocysteine interrelationships in rheumatoid arthritis, coronary artery disease and peripheral artery occlusion disease

“…This is close to the DMA excretion rate of 60 ± 12 mmol DMA/mol creatinine measured in another cohort of 28 patients with rheumatic diseases including RA (Chobanyan-Jürgens et al 2011). Similar excretion rates of DMA (53 ± 2.65 mmol DMA/mol creatinine, n = 49) were also observed in patients suffering from CAD (Tsikas et al 2007). Thus, although patients suffering from RA, PAOD or CAD utilise several times more SAM than healthy subjects to produce ADMA, hCys synthesis seems to be independent of ADMA synthesis in these diseases.…”

“…As neither placebo nor verum changed significantly the plasma concentration of hArg, ADMA and thCys, the combined data are presented here for the whole population. Note the logarithmic scale on the y axis Table 1 Spearman correlation between the indicated analyte pairs before (0) and after 12 weeks (12) of supplementation in the rheumatoid patients studied in this work Data from the placebo and verum groups were combined a P = 0.000003 creatinine (Tsikas et al 2007). This rough calculation suggests that the guanidinoacetate methyltransferase (GAMT)-catalysed synthesis of creatine utilises approximately 100 times more SAM than the PRMT-catalysed synthesis of ADMA in healthy humans (Fig.…”

Association of homoarginine and methylarginines with liver dysfunction and mortality in chronic liver disease

“…The present work extends the current knowledge on ADMA and liver dysfunction by confirming previous data on the association of ADMA with Child-Pugh score (Lluch et al 2004), and by demonstrating for the first time that ADMA is positively correlated with the MELD score. These latter results are likewise the consequence of liver dysfunction related to reduced DDAH activity and probably also increased arginine methylation by type 1 protein arginine N-methyltransferase (PRMT-1) activity, which both contribute to higher circulating ADMA levels (Richir et al 2008;Siroen et al 2004Siroen et al , 2005Nijveldt et al 2003b;Tsikas et al 2007;Becker et al 2009). Elevated ADMA levels in chronic liver disease may have deleterious consequences via inhibition of NO synthesis and consecutive intrahepatic NO deficiency contributing to portal hypertension as well as systemic NO deficiency, which may in turn increase cardiovascular risk (Vizzutti et al 2007;Meinitzer et al 2011b;Nijveldt et al 2003a;Karakurt et al 2009).…”

“…ADMA and SDMA are endogenous inhibitors of nitric oxide (NO) synthase (Tsikas et al 2000a, b) and can thereby contribute to intrahepatic NO deficiency, an important factor for the development of portal hypertension (Laleman et al 2005;Vizzutti et al 2007). Previous studies suggest that liver dysfunction is associated with excess ADMA levels due to both, increased ADMA production by high protein methylation and decreased ADMA degradation by low hepatic DDAH activity (Mookerjee et al 2007a;Richir et al 2008;Siroen et al 2005;Laleman et al 2005;Tsikas et al 2003Tsikas et al , 2007Kasumov et al 2011;Vizzutti et al 2007;Becker et al 2009). By contrast, SDMA levels are considered to be mainly determined by renal SDMA excretion; however, findings in 24 patients undergoing hepatic resection suggest that the liver may also contribute to SDMA elimination (Siroen et al 2005).…”

Asymmetrical Dimethylarginine, Oxidative Stress, and Atherosclerosis

“…In patients with chronic inflammatory rheumatic diseases, serum nitrite concentrations were lower compared with healthy subjects but higher in the patients' synovial fluid, suggesting impaired endothelial NO synthase activity but increased inducible NO synthase activity in the inflamed joint. 2 In coronary artery disease patients without rheumatoid arthritis, 3 as well as in rheumatoid arthritis patients without coronary artery disease, both ADMA synthesis and dimethylarginine dimethylaminohydrolase activity are severalfold elevated compared with healthy controls ( Figure A). Dimethylamine (rϭ0.66; Pϭ0.07) and ADMA (rϭϪ0.79; Pϭ0.02) correlated with 3-nitrotyrosine ( Figure B), a potential biomarker of myeloperoxidase activity.…”