Non-enzymatic nitric oxide synthesis in biological systems

被引:308
作者
Zweier, JL
Samouilov, A
Kuppusamy, P
机构
[1] Johns Hopkins Med Inst, Johns Hopkins Bayview Med Ctr, Mol & Cellular Biophys Labs, Dept Med,Div Cardiol, Baltimore, MD 21224 USA
[2] Johns Hopkins Med Inst, Johns Hopkins Bayview Med Ctr, Electron Paramagnet Resonance Ctr, Baltimore, MD 21224 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS | 1999年 / 1411卷 / 2-3期
关键词
nitric oxide synthesis; nitrite disproportionation; electron paramagnetic resonance; nitric oxide imaging; ischemia; acidosis;
D O I
10.1016/S0005-2728(99)00018-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nitric oxide (NO) is an important regulator of a variety of biological functions, and also has a role in the pathogenesis of cellular injury. It had been generally accepted that NO is solely generated in biological tissues by specific nitric oxide synthases (NOS) which metabolize arginine to citrulline with the formation of NO. However, NO call also be generated in tissues by either direct disproportionation or reduction of nitrite to NO under the acidic and highly reduced conditions which occur in disease states, such as ischemia. This NO formation is not blocked by NOS inhibitors and with long periods of ischemia progressing to necrosis, this mechanism of NO formation predominates. In postischemic tissues, NOS-independent NO generation has been observed to result in cellular injury with a loss of organ function. The kinetics and magnitude of nitrite disproportionation have been recently characterized and the corresponding rate law of NO formation derived. It was observed that the generation and accumulation of NO from typical nitrite concentrations found in biological tissues increases 100-fold when the pH falls from 7.4 to 5.5. It was also observed that ischemic cardiac tissue contains reducing equivalents which reduce nitrite to NO, further increasing the rate of NO formation more than 40-fold. Under these conditions, the magnitude of enzyme-independent NO generation exceeds that which call be generated by tissue concentrations of NOS. The existence of this enzyme-independent mechanism of NO formation has important implications in our understanding of the pathogenesis and treatment of tissue injury. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:250 / 262
页数:13
相关论文
共 39 条
[1]  
AMBROSIO G, 1993, J BIOL CHEM, V268, P18532
[2]   APPARENT HYDROXYL RADICAL PRODUCTION BY PEROXYNITRITE - IMPLICATIONS FOR ENDOTHELIAL INJURY FROM NITRIC-OXIDE AND SUPEROXIDE [J].
BECKMAN, JS ;
BECKMAN, TW ;
CHEN, J ;
MARSHALL, PA ;
FREEMAN, BA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (04) :1620-1624
[3]   STOMACH NO SYNTHESIS [J].
BENJAMIN, N ;
ODRISCOLL, F ;
DOUGALL, H ;
DUNCAN, C ;
SMITH, L ;
GOLDEN, M ;
MCKENZIE, H .
NATURE, 1994, 368 (6471) :502-502
[4]   NITRIC-OXIDE, A NOVEL NEURONAL MESSENGER [J].
BREDT, DS ;
SNYDER, SH .
NEURON, 1992, 8 (01) :3-11
[5]   CLONED AND EXPRESSED NITRIC-OXIDE SYNTHASE STRUCTURALLY RESEMBLES CYTOCHROME-P-450 REDUCTASE [J].
BREDT, DS ;
HWANG, PM ;
GLATT, CE ;
LOWENSTEIN, C ;
REED, RR ;
SNYDER, SH .
NATURE, 1991, 351 (6329) :714-718
[6]   THE OBLIGATORY ROLE OF ENDOTHELIAL-CELLS IN THE RELAXATION OF ARTERIAL SMOOTH-MUSCLE BY ACETYLCHOLINE [J].
FURCHGOTT, RF ;
ZAWADZKI, JV .
NATURE, 1980, 288 (5789) :373-376
[7]   ENDOTHELIUM-DERIVED RELAXING AND CONTRACTING FACTORS [J].
FURCHGOTT, RF ;
VANHOUTTE, PM .
FASEB JOURNAL, 1989, 3 (09) :2007-2018
[8]   SELECTIVE-INHIBITION OF CONSTITUTIVE NITRIC-OXIDE SYNTHASE BY L-N(G)-NITROARGININE [J].
FURFINE, ES ;
HARMON, MF ;
PAITH, JE ;
GARVEY, EP .
BIOCHEMISTRY, 1993, 32 (33) :8512-8517
[10]   GLUTAMATE, NITRIC-OXIDE AND CELL CELL SIGNALING IN THE NERVOUS-SYSTEM [J].
GARTHWAITE, J .
TRENDS IN NEUROSCIENCES, 1991, 14 (02) :60-67