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Complex Interplay of Heme-Copper Oxidases with Nitrite and Nitric Oxide.
Chen, J, Xie, P, Huang, Y, Gao, H
International journal of molecular sciences. 2022;(2)
Abstract
Nitrite and nitric oxide (NO), two active and critical nitrogen oxides linking nitrate to dinitrogen gas in the broad nitrogen biogeochemical cycle, are capable of interacting with redox-sensitive proteins. The interactions of both with heme-copper oxidases (HCOs) serve as the foundation not only for the enzymatic interconversion of nitrogen oxides but also for the inhibitory activity. From extensive studies, we now know that NO interacts with HCOs in a rapid and reversible manner, either competing with oxygen or not. During interconversion, a partially reduced heme/copper center reduces the nitrite ion, producing NO with the heme serving as the reductant and the cupric ion providing a Lewis acid interaction with nitrite. The interaction may lead to the formation of either a relatively stable nitrosyl-derivative of the enzyme reduced or a more labile nitrite-derivative of the enzyme oxidized through two different pathways, resulting in enzyme inhibition. Although nitrite and NO show similar biochemical properties, a growing body of evidence suggests that they are largely treated as distinct molecules by bacterial cells. NO seemingly interacts with all hemoproteins indiscriminately, whereas nitrite shows high specificity to HCOs. Moreover, as biologically active molecules and signal molecules, nitrite and NO directly affect the activity of different enzymes and are perceived by completely different sensing systems, respectively, through which they are linked to different biological processes. Further attempts to reconcile this apparent contradiction could open up possible avenues for the application of these nitrogen oxides in a variety of fields, the pharmaceutical industry in particular.
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Nitrate- and Nitrite-Sensing Histidine Kinases: Function, Structure, and Natural Diversity.
Gushchin, I, Aleksenko, VA, Orekhov, P, Goncharov, IM, Nazarenko, VV, Semenov, O, Remeeva, A, Gordeliy, V
International journal of molecular sciences. 2021;(11)
Abstract
Under anaerobic conditions, bacteria may utilize nitrates and nitrites as electron acceptors. Sensitivity to nitrous compounds is achieved via several mechanisms, some of which rely on sensor histidine kinases (HKs). The best studied nitrate- and nitrite-sensing HKs (NSHKs) are NarQ and NarX from Escherichia coli. Here, we review the function of NSHKs, analyze their natural diversity, and describe the available structural information. In particular, we show that around 6000 different NSHK sequences forming several distinct clusters may now be found in genomic databases, comprising mostly the genes from Beta- and Gammaproteobacteria as well as from Bacteroidetes and Chloroflexi, including those from anaerobic ammonia oxidation (annamox) communities. We show that the architecture of NSHKs is mostly conserved, although proteins from Bacteroidetes lack the HAMP and GAF-like domains yet sometimes have PAS. We reconcile the variation of NSHK sequences with atomistic models and pinpoint the structural elements important for signal transduction from the sensor domain to the catalytic module over the transmembrane and cytoplasmic regions spanning more than 200 Å.
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Therapeutic value of stimulating the nitrate-nitrite-nitric oxide pathway to attenuate oxidative stress and restore nitric oxide bioavailability in cardiorenal disease.
Carlstrom, M, Montenegro, MF
Journal of internal medicine. 2019;(1):2-18
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Abstract
Cardiovascular disorders including hypertension and associated renal disease are major health problems affecting more than 1.5 billion people worldwide. Apart from nonmodifiable factors such as ageing, family history and gender, both sedentary lifestyle and unhealthy dietary habits are considered as major risk factors. The disorders are interrelated suggesting common pathological pathways. Mechanistically, oxidative stress and compromised function of the nitric oxide synthase (NOS) system leading to endothelial dysfunction and reduction in nitric oxide (NO) bioavailability have been widely implicated and associated with development and progression of disease. New strategies that correct this redox imbalance and increase NO bioactivity may have major clinical implications. The inorganic anions, nitrate and nitrite, are endogenously formed by oxidization of NOS-derived NO, but there are also high amounts of nitrate in our daily diet. In this regard, accumulated evidence over the past two decades demonstrates that these anions can be recycled back to NO and other bioactive nitrogen oxides, thus offering an attractive alternative strategy for therapeutic exploitation. In this review, we describe how dietary stimulation of the nitrate-nitrite-NO pathway affects cardiovascular and renal functions in health and disease via modulation of oxidative stress and NO bioavailability. Clinical studies addressing potential effects on the renal system are still limited, but blood pressure-lowering effects of nitrate supplementation have been demonstrated in healthy and hypertensive subjects as well as in patients with chronic kidney disease. However, larger clinical studies are warranted to reveal whether chronic nitrate treatment can slow-down the progression of cardiorenal disease and associated complications.
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A Review of the In Vivo Evidence Investigating the Role of Nitrite Exposure from Processed Meat Consumption in the Development of Colorectal Cancer.
Crowe, W, Elliott, CT, Green, BD
Nutrients. 2019;(11)
Abstract
The World Cancer Research Fund (WCRF) 2007 stated that the consumption of processed meat is a convincing cause of colorectal cancer (CRC), and therefore, the public should avoid it entirely. Sodium nitrite has emerged as a putative candidate responsible for the CRC-inducing effects of processed meats. Sodium nitrite is purported to prevent the growth of Clostridium botulinum and other food-spoiling bacteria, but recent, contradictory peer-reviewed evidence has emerged, leading to media reports questioning the necessity of nitrite addition. To date, eleven preclinical studies have investigated the effect of consuming nitrite/nitrite-containing meat on the development of CRC, but the results do not provide an overall consensus. A sizable number of human clinical studies have investigated the relationship between processed meat consumption and CRC risk with widely varying results. The unique approach of the present literature review was to include analysis that limited the human studies to those involving only nitrite-containing meat. The majority of these studies reported that nitrite-containing processed meat was associated with increased CRC risk. Nitrite consumption can lead to the formation of N-nitroso compounds (NOC), some of which are carcinogenic. Therefore, this focused perspective based on the current body of evidence links the consumption of meat containing nitrites and CRC risk.
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Enhancing mainstream nitrogen removal by employing nitrate/nitrite-dependent anaerobic methane oxidation processes.
Liu, T, Hu, S, Guo, J
Critical reviews in biotechnology. 2019;(5):732-745
Abstract
Due to serious eutrophication in water bodies, nitrogen removal has become a critical stage for wastewater treatment plants (WWTPs) over past decades. Conventional biological nitrogen removal processes are based on nitrification and denitrification (N/DN), and are suffering from several major drawbacks, including substantial aeration consumption, high fugitive greenhouse gas emissions, a requirement for external carbon sources, excessive sludge production and low energy recovery efficiency, and thus unable to satisfy the escalating public needs. Recently, the discovery of anaerobic ammonium oxidation (anammox) bacteria has promoted an update of conventional N/DN-based processes to autotrophic nitrogen removal. However, the application of anammox to treat domestic wastewater has been hindered mainly by unsatisfactory effluent quality with nitrogen removal efficiency below 80%. The discovery of nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) during the last decade has provided new opportunities to remove this barrier and to achieve a robust system with high-level nitrogen removal from municipal wastewater, by utilizing methane as an alternative carbon source. In the present review, opportunities and challenges for nitrate/nitrite-dependent anaerobic methane oxidation are discussed. Particularly, the prospective technologies driven by the cooperation of anammox and n-DAMO microorganisms are put forward based on previous experimental and modeling studies. Finally, a novel WWTP system acting as an energy exporter is delineated.
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6.
Nitrite-induced acute kidney injury with secondary hyperparathyroidism: Case report and literature review.
Peng, T, Hu, Z, Yang, X, Gao, Y, Ma, C
Medicine. 2018;(8):e9889
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Abstract
RATIONALE Acute kidney injury (AKI) with hyperparathyroidism caused by nitrite was rare, and renal function and parathyroid hormone (PTH) decreased to normal range after therapy. PATIENT CONCERNS Acute kidney injury was diagnosed in a 40-year-old male with hyperparathyroidism and cyanosis of his hands and both forearms. DIAGNOSES The patient ate some recently pickled vegetables, and he experienced nausea, vomiting and diarrhoea without oliguria or anuria; Additionally, his hands and both forearms had a typical blue ash appearance. After admission, the laboratory findings indicated theincreasing serum creatinine (Scr) and parathyroid hormone (PTH). He was diagnosed as acute kidney injury with hyperparathyroidism caused by nitrite. INTERVENTIONS The patient stopped eating the pickled vegetables and was given rehydration, added calories and other supportive therapy without any glucocorticoids. OUTCOMES According to his clinical manifestations, laboratory findings and imaging results, the patient was diagnosed with acute kidney injury with secondary hyperparathyroidism. He was given symptomatic supportive care therapy. After one week, the serum creatinine, parathyroid hormone (PTH), hypercalcemia, hyperphosphatemia, proteinuria, and urine red blood cell values decreased to normal range. LESSONS Nitrite-induced acute kidney injury with secondary hyperparathyroidism was relatively rare. After therapy, the function of the kidney and parathyroid returned to normal. This case suggests that detailed collection of medical history, physical examination and correct symptomatic treatment is very important.
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Mechanisms of the bactericidal effects of nitrate and nitrite in cured meats.
Majou, D, Christieans, S
Meat science. 2018;:273-284
Abstract
For cured meat products, nitrite is recognized for its antimicrobial effects against pathogenic bacteria, even though the specific inhibitory mechanisms are not well known. Nitrite contributes to oxidative stress by being the precursor of peroxynitrite (ONOO-), which is the major strong oxidant. Thus, bacterial stress (highly pH-very low partial pressure of oxygen-dependent) is enhanced by the nitrate-nitrite-peroxynitrite system which is also highly pH- and low partial pressure of oxygen-dependent. Nitrite is a hurdle technology which effectiveness depends on several other hurdle technologies including sodium chloride (accelerating the autoxidation of oxymyoglobin and promote peroxynitrite formation), ascorbate (increasing ONOO- synthesis), and Aw. In this environment, certain species are more resistant than others to acidic, oxidative, and nitrative stresses. The most resistant are gram-negative aerobic/facultative anaerobic bacteria (Escherichia coli, Salmonella), and the most fragile are gram-positive anaerobic bacteria (Clostridium botulinum). This position review highlights the major chemical mechanisms involved, the active molecules and their actions on bacterial metabolisms in the meat ecosystem.
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Special Lecture.
Nihon saikingaku zasshi. Japanese journal of bacteriology. 2017;(1):3
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Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm.
Loudon, BL, Noordali, H, Gollop, ND, Frenneaux, MP, Madhani, M
British journal of pharmacology. 2016;(12):1911-24
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Abstract
Many conditions culminate in heart failure (HF), a multi-organ systemic syndrome with an intrinsically poor prognosis. Pharmacotherapeutic agents that correct neurohormonal dysregulation and haemodynamic instability have occupied the forefront of developments within the treatment of HF in the past. Indeed, multiple trials aimed to validate these agents in the 1980s and early 1990s, resulting in a large and robust evidence-base supporting their use clinically. An established treatment paradigm now exists for the treatment of HF with reduced ejection fraction (HFrEF), but there have been very few notable developments in recent years. HF remains a significant health concern with an increasing incidence as the population ages. We may indeed be entering the surgical era for HF treatment, but these therapies remain expensive and inaccessible to many. Newer pharmacotherapeutic agents are slowly emerging, many targeting alternative therapeutic pathways, but with mixed results. Metabolic modulation and manipulation of the nitrate/nitrite/nitric oxide pathway have shown promise and could provide the answers to fill the therapeutic gap between medical interventions and surgery, but further definitive trials are warranted. We review the significant evidence base behind the current medical treatments for HFrEF, the physiology of metabolic impairment in HF, and discuss two promising novel agents, perhexiline and nitrite.
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Nitrate- and nitrite-dependent anaerobic oxidation of methane.
Welte, CU, Rasigraf, O, Vaksmaa, A, Versantvoort, W, Arshad, A, Op den Camp, HJ, Jetten, MS, Lüke, C, Reimann, J
Environmental microbiology reports. 2016;(6):941-955
Abstract
Microbial methane oxidation is an important process to reduce the emission of the greenhouse gas methane. Anaerobic microorganisms couple the oxidation of methane to the reduction of sulfate, nitrate and nitrite, and possibly oxidized iron and manganese minerals. In this article, we review the recent finding of the intriguing nitrate- and nitrite-dependent anaerobic oxidation of methane (AOM). Nitrate-dependent AOM is catalyzed by anaerobic archaea belonging to the ANME-2d clade closely related to Methanosarcina methanogens. They were named 'Candidatus Methanoperedens nitroreducens' and use reverse methanogenesis with the key enzyme methyl-coenzyme M (methyl-CoM) reductase for methane activation. Their major end product is nitrite which can be taken up by nitrite-dependent methanotrophs. Nitrite-dependent AOM is performed by the NC10 bacterium 'Candidatus Methylomirabilis oxyfera' that probably utilizes an intra-aerobic pathway through the dismutation of NO to N2 and O2 for aerobic methane activation by methane monooxygenase, yet being a strictly anaerobic microbe. Environmental distribution, physiological and biochemical aspects are discussed in this article as well as the cooperation of the microorganisms involved.