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Reduction Of Nω-hydroxy-l-arginine To L-arginine By Pig Liver Microsomes, Mitochondria, And Human Liver Microsomes

B. Clement, T. Kunze, Sabine Heberling
Published 2006 · Biology

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Abstract N ω -Hydroxy- l -arginine, the intermediate in nitric oxide formation from l -arginine catalyzed by NO synthase, can be released into the extracellular space. It has been suggested that it can circulate and exert paracrine effects. Since it cannot only be used as substrate by NO synthases, but can also be oxidized by cytochrome P450 and other hemoproteins in a superoxide-dependent manner, it has been proposed that it can serve as NO donor. In the present study, the in vitro reduction of N ω -hydroxy- l -arginine was examined. Pig and human liver microsomes as well as pig liver mitochondria were capable of reducing N ω -hydroxy- l -arginine to l -arginine in an oxygen-insensitive enzymatic reaction. These results demonstrate that this metabolic pathway has to be considered when suggesting N ω -hydroxy- l -arginine as NO-precursor. The reconstituted liver microsomal system of a pig liver CYP2D enzyme, the benzamidoxime reductase, was unable to replace microsomes to produce l -arginine from N ω -hydroxy- l -arginine.
This paper references
N omega-hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine.
D. Stuehr (1991)
10.1074/JBC.271.19.11462
Endothelial Nitric-oxide Synthase
I. Rodríguez-Crespo (1996)
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)
10.1016/0003-2697(85)90442-7
Measurement of protein using bicinchoninic acid.
P. Smith (1985)
10.1016/S0076-6879(78)52024-7
The measurement of difference spectra: application to the cytochromes of microsomes.
R. Estabrook (1978)
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)
10.1021/BI980742T
Substrate Specificity of NO Synthases: Detailed Comparison of l-Arginine, Homo-l-arginine, Their Nω-Hydroxy Derivatives, and Nω-Hydroxynor-l-arginine†
C. Moali (1998)
THE CARBON MONOXIDE-BINDING PIGMENT OF LIVER MICROSOMES. I. EVIDENCE FOR ITS HEMOPROTEIN NATURE.
T. Omura (1964)
10.1096/fasebj.6.12.1381691
Nitric oxide as a secretory product of mammalian cells
C. Nathan (1992)
10.1152/AJPHEART.1996.271.5.H1988
Arginase activity in endothelial cells: inhibition by NG-hydroxy-L-arginine during high-output NO production.
G. Buga (1996)
10.1021/TX9502047
Microsomal catalyzed N-hydroxylation of guanabenz and reduction of the N-hydroxylated metabolite: characterization of the two reactions and genotoxic potential of guanoxabenz.
B. Clement (1996)
10.1016/0014-2999(95)00046-N
Increase in serum NG-hydroxy-L-arginine in rats treated with bacterial lipopolysaccharide.
M. Hecker (1995)
10.1016/0005-2736(90)90036-N
Improved methods to isolate and subfractionate rat liver mitochondria. Lipid composition of the inner and outer membrane.
R. Hovius (1990)
Nitric oxide: physiology, pathophysiology, and pharmacology.
S. Moncada (1991)
10.1016/0300-9084(96)88181-8
On the mechanism of nitric oxide formation upon oxidative cleavage of C = N(OH) bonds by NO-synthases and cytochromes P450.
D. Mansuy (1995)
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)
10.1016/S0076-6879(78)52011-9
[9] Detergent-solubilized NADH-cytochrome b5 reductase
K. Mihara (1978)
10.1136/ard.56.5.330
Increased serum NG-hydroxy-l-arginine in patients with rheumatoid arthritis and systemic lupus erythematosus as an index of an increased nitric oxide synthase activity
R. Wigand (1997)
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)
10.1002/ARDP.19883211228
Enzymatic Reduction of Benzamidoxime to Benzamidoxine
B. Clement (1988)
10.1006/BBRC.1993.2429
N omega-hydroxy-L-arginine, a reactional intermediate in nitric oxide biosynthesis, induces cytostasis in human and murine tumor cells.
B. Chénais (1993)
Some properties of a detergent-solubilized NADPH-cytochrome c(cytochrome P-450) reductase purified by biospecific affinity chromatography.
Y. Yasukochi (1976)
10.1021/TX000043T
Reduction of amphetamine hydroxylamine and other aliphatic hydroxylamines by benzamidoxime reductase and human liver microsomes.
B. Clement (2000)
10.1081/DMR-120005643
REDUCTION OF N-HYDROXYLATED COMPOUNDS: AMIDOXIMES (N-HYDROXYAMIDINES) AS PRO-DRUGS OF AMIDINES
B. Clement (2002)
10.1016/S1357-2725(96)00089-1
Possible mechanism of nitric oxide production from N(G)-hydroxy-L-arginine or hydroxylamine by superoxide ion.
P. Vetrovsky (1996)



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