Comparison of Substrate and Inhibitor Specificity of Arginase and Nitricm Oxide (NO) Synthase for Arginine Analogs and Related Compounds in Murine and Rat Macrophages

Hrabák, A.; Bajor, Tamás; Temesi, A

doi:10.1006/bbrc.1994.1029

Cited by 92 publications

(74 citation statements)

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“…[5][6][7][8] We found an inverse association between homoarginine and markers of impaired endothelial function (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), and we observed lower levels of homoarginine in patients with heart failure than in those without heart failure. In this context, it is of interest that the highest serum levels of homoarginine are found in states of enhanced vasodilation and increased NO production, such as in pregnant women (4.8Ϯ1.7 mol/L in the second trimester and 5.3Ϯ1.5 mol/L in the third trimester).…”

Section: Discussionmentioning

confidence: 48%

“…20 Given the structural similarities between lysine and homoarginine, it is likely that homoarginine inhibits arginase, thus increasing the availability of L-arginine for NO production by NO synthase (Figure 3). 5,20 This latter hypothesis appears to be supported by the observed correlation of homoarginine with an increased arginine-to-ornithine ratio, which is considered an indicator of low arginase activity. 18 However, homoarginine is a less potent inhibitor of arginase than ornithine.…”

Section: Discussionmentioning

confidence: 86%

“…Second, it potentially increases the intracellular concentration of L-arginine, the main substrate for NO synthase, by inhibiting the enzyme arginase, which competes with NO synthase for the key substrate L-arginine. [5][6][7][8] The significance of homoarginine to NO metabolism is not fully understood, but recent evidence suggests that homoarginine is positively related to endothelial function. 7 Homoarginine may exert further actions that are relevant to cardiovascular health, including inhibition of platelet aggregation and stimulation of insulin secretion.…”

Section: Clinical Perspective On P 975mentioning

confidence: 99%

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Homoarginine, Cardiovascular Risk, and Mortality

et al. 2010

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Background-Homoarginine is an amino acid derivative that may increase nitric oxide availability and enhance endothelial function. The effect of the level of homoarginine on cardiovascular outcome and mortality is unknown. Methods and Results-We assessed cardiovascular and all-cause mortality according to homoarginine levels in a cohort of 3305 subjects referred for coronary angiography from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) Study. After investigating the relation of homoarginine with kidney function and markers of endothelial dysfunction, we explored its effects on adverse outcomes in a second high-risk cohort of 1244 patients with type 2 diabetes mellitus receiving maintenance hemodialysis (4D study [Die Deutsche Diabetes Dialyse Studie]). In the LURIC study, mean serum homoarginine levels were 2.6Ϯ1.1 mol/L. During a median follow-up of 7.7 years, 766 patients died. After adjustments for age and sex, patients in the lowest quartile (Ͻ1.85 mol/L) had a Ͼ4-fold higher rate of dying of cardiovascular disease (hazard ratio 4.1, 95% confidence interval 3.0 to 5.7) than patients in the highest quartile (Ͼ3.1 mol/L). Lower homoarginine levels were associated with lower estimated glomerular filtration rate and higher levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Hemodialysed patients had lower mean homoarginine levels of 1.2Ϯ0.5 mol/L and experienced a 5-fold increased mortality rate compared with LURIC patients (608 deaths during a median follow-up of 4 years). Homoarginine consistently affected mortality, which was 2-fold higher in 4D study patients in the lowest quartile (Ͻ0.87 mol/L) than in patients in the highest quartile (Ͼ1.4 mol/L). Conclusions-Homoarginine levels are independently associated with cardiovascular and all-cause mortality in patients referred for coronary angiography and in patients undergoing hemodialysis. Future studies are needed to elucidate the underlying pathomechanisms. (Circulation. 2010;122:967-975.)

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Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 86%

Section: Clinical Perspective On P 975mentioning

confidence: 99%

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Homoarginine, Cardiovascular Risk, and Mortality

et al. 2010

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“…8 Several functional studies have demonstrated that L-homoarginine, in addition to L-arginine, can act as a substrate for NO production by NOS [17][18][19]38 (Fig 1) and pregnancy is associated with reprogramming of cell signalling in response to the increased consumption of NO. 39 Gerritsen et al have observed L-homocitrulline in the urine of newborns, but not in adults, and NOS enzyme is known to convert L-homoarginine to L-homocitrulline releasing NO.…”

Section: Discussionmentioning

confidence: 99%

Serum L-Homoarginine Concentration is Elevated During Normal Pregnancy and is Related to Flow-Mediated Vasodilatation

Valtonen

Laitinen

Lyyra-Laitinen

et al. 2008

Circ J

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“…Thus use of NOS inhibitors that are taken up via system y + may limit the availability of arginine for other enzymes that utilize this amino acid. It is important to note that N G -monomethyl--arginine, N G -nitro--arginine, N G -nitro--arginine methyl ester and aminoguanidine have no significant activity as direct inhibitors of arginase [176,177].…”

Section: Arginine Transportmentioning

confidence: 99%

Arginine metabolism: nitric oxide and beyond

Morris

1998

Biochemical Journal

2,424

2,036

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Arginine is one of the most versatile amino acids in animal cells, serving as a precursor for the synthesis not only of proteins but also of nitric oxide, urea, polyamines, proline, glutamate, creatine and agmatine. Of the enzymes that catalyse rate-controlling steps in arginine synthesis and catabolism, argininosuccinate synthase, the two arginase isoenzymes, the three nitric oxide synthase isoenzymes and arginine decarboxylase have been recognized in recent years as key factors in regulating newly identified aspects of arginine metabolism. In particular, changes in the activities of argininosuccinate synthase, the arginases, the inducible isoenzyme of nitric oxide synthase and also cationic amino acid transporters play major roles in determining the metabolic fates of arginine in health and disease, and recent studies have identified

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Comparison of Substrate and Inhibitor Specificity of Arginase and Nitricm Oxide (NO) Synthase for Arginine Analogs and Related Compounds in Murine and Rat Macrophages

Cited by 92 publications

References 0 publications

Homoarginine, Cardiovascular Risk, and Mortality

Homoarginine, Cardiovascular Risk, and Mortality

Serum L-Homoarginine Concentration is Elevated During Normal Pregnancy and is Related to Flow-Mediated Vasodilatation

Arginine metabolism: nitric oxide and beyond

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