Radical reactions of nitric oxide synthases

2004 ◽  
Vol 71 ◽  
pp. 39-49 ◽  
Author(s):  
Dennis J. Stuehr ◽  
Chin-Chuan Wei ◽  
Jerome Santolini ◽  
Zhi- Qiang Wang ◽  
Mika Aoyagi ◽  
...  

NOSs (nitric oxide synthases) are flavohaem enzymes that function broadly in human health and disease. We are combining mutagenesis, crystallographic and rapid kinetic methods to understand their mechanism and regulation. The NOSs create a transient tetrahydrobiopterin radical within the enzyme to generate their free radical product (NO). Recent work is revealing how critically important this process is at all levels of catalysis. This article will synthesize four seemingly disparate but related aspects of NOS tetrahydrobiopterin radical formation: (i) how it enables productive O2 activation by providing an electron to the enzyme haem, (ii) what structural features help to regulate this electron transfer, (iii) how it enables NOS to synthesize NO from its diamagnetic substrate and (iv) how it allows NOS to release NO after each catalytic cycle instead of other nitorgen oxide-containing products.

2001 ◽  
Vol 276 (23) ◽  
pp. 20116-20124 ◽  
Author(s):  
Clinton R. Nishida ◽  
Paul R. Ortiz de Montellano

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17508-e17508
Author(s):  
Natalia V. Chernikova ◽  
Irina A. Goroshinskaya ◽  
Elena M. Frantsiyants ◽  
Ekaterina V. Verenikina ◽  
Yuriy A. Poryvaev ◽  
...  

e17508 Background: Cervical cancer (CC) is one of the main causes of death among patients with gynecological tumors. As a rule, patients die from relapses and metastases which rates reach 30-45%. According to research data, treatment of patients with distant metastases is ineffective, and half of them die within 9.7 months, while the average survival is 15.9±0.26 months. The development of many pathological processes is considered to be associated with an increase in free-radical reactions leading to oxidative damage to various biomolecules. The purpose of the study was to analyze some characteristics of the free-radical oxidation and antioxidant defence in metastasizing CC. Methods: The study included 56 patients aged 29-73 years with stage IIB-IV CC after antitumor treatment. The main group – 27 patients who developed metastases within 4 months to 8 years after the CC diagnosis; controls – 29 patients with non-metastatic CC; donors – 19 healthy women aged 27-61 years. The accumulation of carbonyl derivatives in blood plasma proteins was detected in the reaction with 2, 4-dinitrophenylhydrazine. The induced oxidative modification of proteins was stimulated with Fenton's reagent. Free-radical processes was evaluated by the intensity of peroxide-induced luminol-dependent plasma chemiluminescence and the content of nitric oxide metabolites; the intensity of lipid peroxidation - by the content of malondialdehyde (MDA); the activity of catalase and ceruloplasmin was also studied. Results: CC progression was accompanied by increasing lipid peroxidation and spontaneous oxidation of blood plasma proteins. MDA levels in patients with metastases increased by 57.8% compared to donors and by 34.3% compared to patients without metastases (p < 0.05). The concentration of 2, 4-dinitrophenylhydrozones increased on average by 4 times compared to donors and by almost 2 times compared to patients without metastases. Patients with metastasizing CC demonstrated elevated levels of products of the interaction of nitric oxide and its derivatives with proteins and peptides - 3-nitrotyrosine and nitrosoglutathione, compared to both donors (by 31.4% and 55.3%) and patients in remission (by 38.1% and 34.5%). Chemiluminescence activity increased by 54.5% compared to donors (p < 0.05) and by 93% (p < 0.01) compared to controls. Catalase activity in the blood plasma of patients with metastases increased by 54.1% compared to donors, but was lower than the values in the control group (by 22.1%). Ceruloplasmin activity was increased only in patients without metastases (by 33%). Conclusions: The process of CC metastasis is accompanied by a greater intensity of oxidative processes of both proteins and lipids, as well as depletion of the adaptive capabilities of the body's antioxidant system.


1977 ◽  
Vol 67 (3) ◽  
pp. 1211 ◽  
Author(s):  
William A. Bernhard ◽  
David M. Close ◽  
Jürgen Hüttermann ◽  
Herbert Zehner

2014 ◽  
Vol 130 ◽  
pp. 130-140 ◽  
Author(s):  
Changjian Feng ◽  
Li Chen ◽  
Wenbing Li ◽  
Bradley O. Elmore ◽  
Wenhong Fan ◽  
...  

1978 ◽  
Vol 6 (5) ◽  
pp. 962-964 ◽  
Author(s):  
A. INGALL ◽  
K. A. K. LOTT ◽  
T. F. SLATER ◽  
S. FINCH ◽  
A. STIER

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