Online citations, reference lists, and bibliographies.
← Back to Search

Nδ-Methylated L-arginine Derivatives And Their Effects On The Nitric Oxide Generating System

J. Kotthaus, Dennis Schade, Katrin Töpker-Lehmann, E. Beitz, B. Clement
Published 2008 · Chemistry

Cite This
Download PDF
Analyze on Scholarcy
Share
Abstract So far N δ -methyl- l -arginine (MA) is only detected in yeast cells. Assuming that MA also exists in mammalians we examined possible physiological effects of N δ -methylated l -arginine derivatives on the nitric oxide generating system, that is, nitric oxide synthase (NOS), arginase and dimethylarginine dimethylaminohydrolase (DDAH). N δ -methyl- l -citrulline (MC) turned out to be a weak non-specific inhibitor of nitric oxide synthases. Moreover, MA is hydroxylated by all human NOS isoforms to N ω -hydroxy- N δ -methyl- l -arginine (NHAM) but not converted further. This hydroxylated intermediate, however, was detected to be a potent inhibitor of bovine liver arginase with a K i of 17.1 ± 2.2 μM.
This paper references
Reactions and significance of cytochrome P-450 enzymes.
F. Guengerich (1991)
10.1074/jbc.272.10.6114
Mutation of Glu-361 in Human Endothelial Nitric-oxide Synthase Selectively Abolishes L-Arginine Binding without Perturbing the Behavior of Heme and Other Redox Centers*
P. Chen (1997)
10.1021/BI981175C
Microsomal cytochrome P450 dependent oxidation of N-hydroxyguanidines, amidoximes, and ketoximes: mechanism of the oxidative cleavage of their C=N(OH) bond with formation of nitrogen oxides.
A. Jousserandot (1998)
10.1111/j.1524-6175.2006.06025.x
Nitric Oxide in the Pathogenesis of Cardiac Disease
L. Raij (2006)
10.1074/jbc.274.2.814
S-Adenosylmethionine-dependent Methylation in Saccharomyces cerevisiae
A. Niewmierzycka (1999)
10.1161/01.HYP.0000146907.82869.f2
Upregulation of Vascular Arginase in Hypertension Decreases Nitric Oxide–Mediated Dilation of Coronary Arterioles
C. Zhang (2004)
10.1042/bj3570593
Nitric oxide synthases: structure, function and inhibition.
W. K. Alderton (2001)
10.1021/JM970550G
Potent and selective inhibition of neuronal nitric oxide synthase by N(ω)-propyl-L-arginine
H. Q. Zhang (1997)
10.1111/j.1476-5381.1996.tb16010.x
2‐Amino‐4‐methylpyridine as a potent inhibitor of inducible NO synthase activity in vitro and in vivo
W. S. Faraci (1996)
10.1136/BMJ.1.5011.149-A
ADVANCES IN PHARMACOLOGY
J. H. Burn (1957)
10.1096/fj.04-2317fje
Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension
W. Xu (2004)
10.1074/jbc.272.31.19615
Isolation and Characterization of the Protein Components of the Liver Microsomal O2-insensitive NADH-Benzamidoxime Reductase*
B. Clement (1997)
10.1016/J.NUMECD.2005.11.012
Endothelial dysfunction and oxidative stress in arterial hypertension.
P. Ferroni (2006)
10.1074/jbc.273.45.29283
δ-N-Methylarginine Is a Novel Posttranslational Modification of Arginine Residues in Yeast Proteins*
P. Zobel-Thropp (1998)
10.1006/BBRC.1993.1380
Particular ability of liver P450s3A to catalyze the oxidation of N omega-hydroxyarginine to citrulline and nitrogen oxides and occurrence in no synthases of a sequence very similar to the heme-binding sequence in P450s.
J. P. Renaud (1993)
10.1016/J.PHARMTHERA.2004.11.011
Nitric oxide and penile erectile function.
N. Toda (2005)
10.1002/CBER.187901201117
Bemerkungen zu der Abhandlung der HH. Weselsky und Benedikt „Ueber einige Azoverbindungen”
P. Griess (1879)
10.1007/s007750050025
Nω-Hydroxyamino-α-amino acids as a new class of very strong inhibitors of arginases
J. Custot (1996)
10.1021/JA970285O
The new alpha-amino acid N-omega-hydroxy-nor-L-arginine: A high-affinity inhibitor of arginase well adapted to bind to its manganese cluster
J. Custot (1997)
Purification and properties of a new enzyme, NG,NG-dimethylarginine dimethylaminohydrolase, from rat kidney.
T. Ogawa (1989)
10.1006/BBRC.1994.1909
Inhibition of rat liver arginase by an intermediate in NO biosynthesis, NG-hydroxy-L-arginine: implications for the regulation of nitric oxide biosynthesis by arginase.
F. Daghigh (1994)
10.1016/0006-291X(92)91279-Y
Cytochrome P450 catalyzes the oxidation of N omega-hydroxy-L-arginine by NADPH and O2 to nitric oxide and citrulline.
J. L. Boucher (1992)
10.1021/JM050187A
Selective substrate-based inhibitors of mammalian dimethylarginine dimethylaminohydrolase.
S. Rossiter (2005)
10.1074/jbc.274.36.25218
l-Arginine Binding to Nitric-oxide Synthase
B. R. Babu (1999)
10.1006/BBRC.2000.2474
A potent inhibitor of inducible nitric oxide synthase, ONO-1714, a cyclic amidine derivative.
M. Naka (2000)
10.1006/BBRC.1994.2371
N omega-hydroxyl-L-arginine, an intermediate in the L-arginine to nitric oxide pathway, is a strong inhibitor of liver and macrophage arginase.
J. L. Boucher (1994)
10.1016/S0006-2952(99)00102-1
Microsomal formation of nitric oxide and cyanamides from non-physiological N-hydroxyguanidines: N-hydroxydebrisoquine as a model substrate.
B. Clement (1999)
10.1016/S0021-9673(99)00942-5
Retention/quantitation properties of the o-phthaldialdehyde-3-mercaptopropionic acid and the o-phthaldialdehyde-N-acetyl-L-cysteine amino acid derivatives in reversed-phase high-performance liquid chromatography.
A. Vasanits (2000)
10.1021/BI010783G
Classical and slow-binding inhibitors of human type II arginase.
D. M. Colleluori (2001)
10.1016/0006-2952(93)90616-5
Cytochrome P450 dependent N-hydroxylation of a guanidine (debrisoquine), microsomal catalysed reduction and further oxidation of the N-hydroxy-guanidine metabolite to the urea derivative. Similarity with the oxidation of arginine to citrulline and nitric oxide.
B. Clement (1993)
10.1021/JM00033A004
Synthesis of L-thiocitrulline, L-homothiocitrulline, and S-methyl-L-thiocitrulline: a new class of potent nitric oxide synthase inhibitors.
K. Narayanan (1994)
10.1016/J.BMCL.2005.05.088
L-arginine analogs as alternate substrates for nitric oxide synthase.
Scott D. Luzzi (2005)
10.1161/01.CIR.0000142867.26182.32
Thrombin Stimulates Human Endothelial Arginase Enzymatic Activity via RhoA/ROCK Pathway: Implications for Atherosclerotic Endothelial Dysfunction
X. Ming (2004)
10.1007/s000180050352
Nitric oxide biosynthesis, nitric oxide synthase inhibitors and arginase competition for L-arginine utilization
J. L. Boucher (1999)
10.1016/0378-4347(88)80031-8
Determination of agmatine, arginine, citrulline and ornithine by reversed-phase liquid chromatography using automated pre-column derivatization with o-phthalaldehyde.
M. Patchett (1988)
10.1016/J.BBRC.2006.08.123
Reduction of Nω-hydroxy-l-arginine to l-arginine by pig liver microsomes, mitochondria, and human liver microsomes
B. Clement (2006)
10.1021/TX0001068
Oxidations of N(omega)-hydroxyarginine analogues and various N-hydroxyguanidines by NO synthase II: key role of tetrahydrobiopterin in the reaction mechanism and substrate selectivity.
C. Moali (2001)
10.1042/BJ3200193
Identification of the 4-amino analogue of tetrahydrobiopterin as a dihydropteridine reductase inhibitor and a potent pteridine antagonist of rat neuronal nitric oxide synthase.
E. Werner (1996)
10.1021/BI00088A020
NG-methyl-L-arginine functions as an alternate substrate and mechanism-based inhibitor of nitric oxide synthase.
N. M. Olken (1993)



This paper is referenced by
10.1002/cbic.201200499
Dimethylarginine‐Dimethylaminohydrolase‐2 (DDAH‐2) Does Not Metabolize Methylarginines
Karin S Altmann (2012)
10.1002/ardp.200900060
Arylazoamidoximes and Related Compounds as NO‐modulators
A. Schroeder (2010)
10.1039/c0ob01117g
Prodrug design for the potent cardiovascular agent Nω-hydroxy-L-arginine (NOHA): synthetic approaches and physicochemical characterization.
D. Schade (2011)
10.3109/14756366.2011.573480
Designing modulators of dimethylarginine dimethylaminohydrolase (DDAH): A focus on selectivity over arginase
J. Kotthaus (2012)
10.1016/j.jprot.2013.01.003
MS³ fragmentation patterns of monomethylarginine species and the quantification of all methylarginine species in yeast using MRM³.
T. Lakowski (2013)
10.1021/bi301571v
Methylated N(ω)-hydroxy-L-arginine analogues as mechanistic probes for the second step of the nitric oxide synthase-catalyzed reaction.
Kristin Jansen Labby (2013)
10.1042/BJ20100960
Reduction of N(ω)-hydroxy-L-arginine by the mitochondrial amidoxime reducing component (mARC).
J. Kotthaus (2011)
10.1016/j.pharmthera.2010.02.005
Modulating the NO generating system from a medicinal chemistry perspective: current trends and therapeutic options in cardiovascular disease.
D. Schade (2010)
10.1038/s41598-017-13366-4
Arginase Structure and Inhibition: Catalytic Site Plasticity Reveals New Modulation Possibilities
J. Mortier (2017)
10.1016/j.ab.2015.10.001
First detection and quantification of N(δ)-monomethylarginine, a structural isomer of N(G)-monomethylarginine, in humans using MS(3).
J. Martens-Lobenhoffer (2016)
10.1016/j.bmc.2008.10.058
Structure-activity relationship of novel and known inhibitors of human dimethylarginine dimethylaminohydrolase-1: alkenyl-amidines as new leads.
J. Kotthaus (2008)
10.1007/s10337-016-3197-7
Separation of the Structural Isomers of Monomethylarginine in Human Plasma by 2-D-HPLC and MS–MS Detection
J. Martens-Lobenhoffer (2016)
Semantic Scholar Logo Some data provided by SemanticScholar