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Research Article Open access CC BY 4.0

Nitrate Metabolism: A Curse or Blessing to Humanity?

Daniel A. Nnate, Ngozi K. Achi

Journal of Scientific Research and Reports · pp. 1–19 · Published 24 Jul 2016

10.9734/JSRR/2016/26773

Abstract

Nitrate (NO3ˉ) is a metabolic waste produced in humans during the detoxification of nitric oxide (NO). Nitric oxide is responsible for the regulation of blood flow, cell signaling and host defense in a number of mammalian tissues. Shortly after synthesis, nitric oxide is oxidized to nitrate in order to terminate its effect. NO can also be synthesized by an alternative mechanism that relies on the sequential reduction of nitrate to nitrite (NO2ˉ); thereby making nitrite a storage pool that can be reduced to NO under appropriate condition with a concomitant increase in the methemoglobin (metHb) concentration. The NO and metHb produced can result to adverse health effects if not detoxified. NADH-methemoglobin reductase accounts for most metHb reduction. Nitric oxide dioxygenases (NODs) catalyze the conversion of NO to NO3ˉ­­­­­ which help to protect cells from NO poisoning. Nitrate and its reduction products are involved in the modification of the body’s physiological functions. We are exposed to nitrate from dietary intake and nitric oxide oxidation. Nitrate metabolism becomes a threat when nitrate is consumed in excess and the body lacks the enzymes that catalyze the detoxification of its byproducts. During such condition, the hemoglobin, nucleic acids, dietary amines and glycoproteins acts as the primary molecule that mediates its effects. Nitrate is a potential therapeutic agent in the prevention of cardiovascular diseases and improving cell viability. This review serves to reevaluate nitrate metabolism in human with the intentions of understanding its role in NO homeostasis and its metabolic effect due to excess intake.

Nitrite nitric oxide nitrogen dioxide methemoglobin peroxynitrite nitric oxide dioxygenase dietary amines

References (82)

  1. 1 Nitric oxide: physiology, pathophysiology, and pharmacology. [DOI]
  2. 2 Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly [DOI]
  3. 3 Principles of biochemistry [DOI]
  4. 4 Nitric oxide as a secretory product of mammalian cells [DOI]
  5. 5 DNA damage and mutation in human cells exposed to nitric oxide in vitro. [DOI]
  6. 6 Formation of N-nitroso compounds: Chemistry, kinetics, and in vivo occurrence [DOI]
  7. 7 Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury. [DOI]
  8. 8 Superoxide Generation from Endothelial Nitric-oxide Synthase [DOI]
  9. 9 Deoxymyoglobin Is a Nitrite Reductase That Generates Nitric Oxide and Regulates Mitochondrial Respiration [DOI]
  10. 10 Cobalamin‐dependent methionine synthase [DOI]
  11. 11 Complex Inhibitory Effects of Nitric Oxide on Autophagy [DOI]
  12. 12 Chemical synthesis of nitric oxide in the stomach from dietary nitrate in humans. [DOI]
  13. 13 Cobalamin Deficiency: Clinical Picture and Radiological Findings [DOI]
  14. 14 Kinetics and mechanism of the oxidation of human deoxyhemoglobin by nitrites. [DOI]
  15. 15 Formation of 8-nitroguanine by the reaction of guanine with peroxynitrite in vitro [DOI]
  16. 16 Nitric oxide dioxygenase function and mechanism of flavohemoglobin, hemoglobin, myoglobin and their associated reductases [DOI]
  17. 17 Production of nitric oxide and superoxide by activated macrophages and killing of Leishmania major [DOI]
  18. 18 Nitric Oxide and Myoglobins [DOI]
  19. 19 Nitrite: A physiological store of nitric oxide and modulator of mitochondrial function [DOI]
  20. 20 Oxidant/Antioxidant Imbalance and the Risk of Alzheimer's Disease [DOI]
  21. 21 Acceleration of Peroxynitrite Oxidations by Carbon Dioxide [DOI]
  22. 22 Nitric Oxide Induces Oxidative Damage in Addition to Deamination in Macrophage DNA [DOI]
  23. 23 Flavohemoglobin Detoxifies Nitric Oxide in Aerobic, but Not Anaerobic, Escherichia coli [DOI]
  24. 24 Competition for hydrogen between sulphate‐reducing bacteria and methanogenic bacteria from the human large intestine [DOI]
  25. 25 Nitric Oxide Fully Protects against UVA-induced Apoptosis in Tight Correlation with Bcl-2 Up-regulation [DOI]
  26. 26 Myoglobin: cytochrome b5 interactions and the kinetic mechanism of metmyoglobin reductase. [DOI]
  27. 27 Reaction of Human Hemoglobin with Peroxynitrite [DOI]
  28. 28 Kinetics of N-Nitrosation in Oxygenated Nitric Oxide Solutions at Physiological pH: Role of Nitrous Anhydride and Effects of Phosphate and Chloride [DOI]
  29. 29 Localization of metmyoglobin-reducing enzyme (NADH-cytochrome b5 reductase) system components in bovine skeletal muscle [DOI]
  30. 30 Physiological and Molecular Aspects of Cobalamin Transport [DOI]
  31. 31 Nitric Oxide-dependent Processing of Heparan Sulfate in Recycling S-Nitrosylated Glypican-1 Takes Place in Caveolin-1-containing Endosomes [DOI]
  32. 32 The Blue Baby Syndrome [DOI]
  33. 33 Integral membrane heparan sulfate proteoglycans [DOI]
  34. 34 Role of myoglobin in the oxygen supply to red skeletal muscle [DOI]
  35. 35 Peroxynitrite Causes DNA Nicks in Plasmid pBR322 [DOI]
  36. 36 Cholesteryl Ester Is Transported from Caveolae to Internal Membranes as Part of a Caveolin-Annexin II Lipid-Protein Complex [DOI]
  37. 37 Dissimilatory nitrate reduction by a strain ofDesulfovibrio desulfuricans [DOI]
  38. 38 Constitutive and Adaptive Detoxification of Nitric Oxide in Escherichia coli [DOI]
  39. 39 Redox reactivity of iron(III) porphyrins and heme proteins with nitric oxide. Nitrosyl transfer to carbon, oxygen, nitrogen and sulfur [DOI]
  40. 40 Effects of Phenoxyherbicides and Glyphosate on the Hepatic and Intestinal Biotransformation Activities in the Rat [DOI]
  41. 41 Nitrosyl-Heme Complexes Are Formed in the Ischemic Heart [DOI]
  42. 42 Definition and distinction between assimilatory, dissimilatory and respiratory pathways [DOI]
  43. 43 In search of an enzyme: the β-secretase of Alzheimer's disease is an aspartic proteinase [DOI]
  44. 44 The impact of nitrite and antioxidants on ultraviolet-A-induced cell death of human skin fibroblasts [DOI]
  45. 45 Elucidations of the Catalytic Cycle of NADH-Cytochrome b5 Reductase by X-ray Crystallography: New Insights into Regulation of Efficient Electron Transfer [DOI]
  46. 46 Clinical and MRI manifestations of nitrous oxide induced vitamin B12 deficiency: A case report.
  47. 47 Characterization of the purified NADH-cytochrome b5 reductase of human erythrocytes as a FAD-containing enzyme. [DOI]
  48. 48 Infantile methemoglobinemia associated with acute diarrheal illness [DOI]
  49. 49 Receptor‐mediated endocytosis of the intrinsic factor—cobalamin complex in HT 29, a human colon carcinoma cell line [DOI]
  50. 50 The chemistry of nitric oxide-induced deamination and cross-linking of DNA
  51. 51 Autophagy in the Pathogenesis of Disease [DOI]
  52. 52 The L-Arginine-Nitric Oxide Pathway [DOI]
  53. 53 Functions of Cell Surface Heparan Sulfate Proteoglycans [DOI]
  54. 54 Oxidative Stress and the Pathogenesis of Alzheimer's Disease [DOI]
  55. 55 Intragastric nitric oxide production in humans: measurements in expelled air. [DOI]
  56. 56 Prokaryotic Nitrate Reduction: Molecular Properties and Functional Distinction among Bacterial Nitrate Reductases [DOI]
  57. 57 Nitric oxide dioxygenase: An enzymic function for flavohemoglobin [DOI]
  58. 58 Myoglobin function reassessed [DOI]
  59. 59 Vitamin B12Deficiency [DOI]
  60. 60 NO sensing by FNR: regulation of the Escherichia coli NO‐detoxifying flavohaemoglobin, Hmp [DOI]
  61. 61 Disrupted Autophagy Leads to Dopaminergic Axon and Dendrite Degeneration and Promotes Presynaptic Accumulation of α-Synuclein and LRRK2 in the Brain [DOI]
  62. 62 Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases [DOI]
  63. 63 Respiratory Detoxification of Nitric Oxide by the Cytochromec Nitrite Reductase of Escherichia coli [DOI]
  64. 64 Nitrite Curing of Meat: The N-Nitrosamine Problem and Nitrite Alternatives
  65. 65 Mechanism of Carbon Dioxide-Catalyzed Oxidation of Tyrosine by Peroxynitrite [DOI]
  66. 66 Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer's β-secretase [DOI]
  67. 67 Molecular genetics of mucopolysaccharidosis type IIIA and IIIB: Diagnostic, clinical, and biological implications [DOI]
  68. 68 Protection against oral and gastrointestinal diseases: Importance of dietary nitrate intake, oral nitrate reduction and enterosalivary nitrate circulation [DOI]
  69. 69 Hemoglobin: A Nitric-Oxide Dioxygenase [DOI]
  70. 70 Evidence for Mutagenesis by Nitric Oxide during Nitrate Metabolism in Escherichia coli [DOI]
  71. 71 Formation and metabolism of N-nitrosamines
  72. 72 Nitrosative stress in Escherichia coli: reduction of nitric oxide [DOI]
  73. 73 Kinetic and spectroscopic characterization of an intermediate peroxynitrite complex in the nitrogen monoxide induced oxidation of oxyhemoglobin [DOI]
  74. 74 Reactions of nitric oxide with methemoglobin [DOI]
  75. 75 The effects of nitrous oxide on cobalamins, folates, and on related events [DOI]
  76. 76 The metabolism of dietary nitrites and nitrates [DOI]
  77. 77 The Role of Photolabile Dermal Nitric Oxide Derivates in Ultraviolet Radiation (UVR)-Induced Cell Death [DOI]
  78. 78 Reclassification of the sulfate- and nitrate-reducing bacterium Desulfovibrio vulgaris subsp. oxamicus as Desulfovibrio oxamicus sp. nov., comb. nov. [DOI]
  79. 79 Is Endothelial Nitric Oxide Synthase a Moonlighting Protein Whose Day Job is Cholesterol Sulfate Synthesis? Implications for Cholesterol Transport, Diabetes and Cardiovascular Disease [DOI]
  80. 80 Residues in the Distal Heme Pocket of Arabidopsis Non-Symbiotic Hemoglobins: Implication for Nitrite Reductase Activity [DOI]
  81. 81 Nitric Oxide and Inflammatory Bowel Disease: Evidence for Local Intestinal Production in Children with Active Colonic Disease [DOI]
  82. 82 Nitrates and Nitrites: Ingestion, Pharmacodynamics, and Toxicology [DOI]

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