Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2

Background: Nitrite reduction pathways are critical for biological NO production under hypoxia. Results: The mitochondrial enzyme mARC reduces nitrite to NO using cytochrome b5 as electron donor. Conclusion:mARCforms an electron transfer chain withNADH,cytochrome b5, and cytochrome b5 reductase to reduce nitrite to NO. Significance: mARC proteins may constitute a new pathway for hypoxic NO production in vivo. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A

From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications

Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N′-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients.Fil: Stanfill, Stephen B.. National Center For Environmental Health; Estados UnidosFil: Hecht, Stephen S.. University of Minnesota; Estados UnidosFil: Joerger, Andreas C.. Goethe Universitat Frankfurt; AlemaniaFil: González, Pablo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; ArgentinaFil: Maia, Luisa B.. Universidade Nova de Lisboa; PortugalFil: Rivas, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; ArgentinaFil: Moura, José J. G.. Universidade Nova de Lisboa; PortugalFil: Gupta, Alpana K.. Independent Research Consultant; IndiaFil: Le Brun, Nick E.. University of East Anglia; Reino UnidoFil: Crack, Jason C.. University of East Anglia; Reino UnidoFil: Hainaut, Pierre. Universite Grenoble Alpes; FranciaFil: Sparacino Watkins, Courtney. Univeristy of Pittsburgh. School of Medicine; Estados Unidos. Vascular Medicine Institute; Estados UnidosFil: Tyx, Robert E.. National Center For Environmental Health; Estados UnidosFil: Pillai, Suresh D.. Texas A&M University; Estados UnidosFil: Zaatari, Ghazi S.. American University Of Beirut; LíbanoFil: Henley, S. Jane. Centers for Disease Control and Prevention; Estados UnidosFil: Blount, Benjamin C.. National Center For Environmental Health; Estados UnidosFil: Watson, Clifford H.. National Center For Environmental Health; Estados UnidosFil: Kaina, Bernd. University Medical Center; AlemaniaFil: Mehrotra, Ravi. Innovation And Policy Foundation; Indi

Established and proposed roles of xanthine oxidoreductase in oxidative and reductive pathways in plants

Xanthine oxidoreductase (XOR) is among the most-intensively studied enzymes known to participate in the consumption of oxygen in cells. However, it attracted the attention of researchers due its participation in free radical production in vivo, mainly through the production of superoxide radicals. In plants, XOR is a key enzyme in purine degradation where it catalyzes the oxidation of hypoxanthine to xanthine and of xanthine to uric acid. Both reactions are accompanied by electron transfer to either NAD+ with simultaneous formation of NADH or to molecular oxygen, which results in formation of superoxides. Characterization of plant XOR mutants and isolated XOR proteins from various plant species provided evidence that the enzyme plays significant roles in plant growth, leaf senescence, fruit size, synthesis of nitrogen storage compounds, and plant-pathogen interactions. Moreover, the ability of XOR to carry out redox reactions as NADH oxidase and to produce reactive oxygen species and nitric oxide, together with a possible complementary role in abscisic acid synthesis have raised further attention on the importance of this enzyme. Based on these established and proposed functions, XOR is discussed as regulator of different processes of interest in plant biology and agriculture.The authors acknowledge the support of the research grants AGL2010-16167 to J.F.M. from the Spanish Ministry of Science and Innovation and Bi 1075/5-1 to F.B. by the Deutsche Forschungsgemeinschaft. R.E. received a JAE-Doctor grant from the Spanish Research Council (CSIC).