Nitrite And Hemoglobin: The Role Of Nitrite In Hemoglobin-mediated Hypoxic Vasodilation

Discussion in 'Scientific Studies' started by md_a, Apr 21, 2020.

  1. md_a

    md_a Member

    Aug 31, 2015
    The reaction between nitrite and hemoglobin: the role of nitrite in hemoglobin-mediated hypoxic vasodilation


    The reaction between nitrite and hemoglobin has been studied for over a century. However, recent evidence indicating nitrite is a latent vasodilatory agent that can be activated by its reaction with deoxyhemoglobin has led to renewed interest in this reaction. In this review we survey, in the context of our own recent studies, the chemical reactivity of nitrite with oxyhemoglobin, deoxyhemoglobin and methemoglobin, and place these reactions in both a physiological and pharmacological/therapeutic context.

    1. Introduction

    Recent evidence suggests that plasma nitrite anion represents a latent substance that can be activated by hemoglobin in areas of hypoxia to elicit vasodilation

    [1]. The mechanisms by which activation and vasodilation occur are currently uncertain and are under intense study.

    . The chemistry of the nitrite/hemoglobin reaction

    2.1. The reaction between nitrite and oxyhemoglobin

    Ask most researchers in the nitric oxide or hemoglobin fields ‘‘what happens when you mix nitrite with oxyHb’’ and they will say the same thing: nitrite gets oxidized to nitrate and the hemoglobin gets oxidized to the ferric form (methemoglobin or metHb). Ask these same researchers for the mechanism and you will likely also get the same answer: ‘‘It’s complicated!’’ Nevertheless there is often an underlying assumption that this reaction must be responsible for the oxidation of nitrite to nitrate in the blood stream, is perhaps the most important factor in determining why nitrate and not nitrite is the predominant metabolite of nitric oxide in vivo, and is why plasma nitrite is maintained at low- to sub-micromolar levels.

    Summary and conclusions

    Fig. 2 summarizes the essential features of the nitrite/ hemoglobin hypothesis. The interaction of nitrite with deoxyHb and not oxyHb generates a diffusible vasodilator with the properties of nitric oxide. The barrier to diffusion that exists at the red cell membrane will limit the ability of red cells to destroy NO generated in the extracellular space and allow diffusion of red-cell generated NO to the smooth muscle tissue. The major fundamental differences of the nitrite/hemoglobin hypothesis and the S-nitrosohemoglobin hypothesis are that hemoglobin does not carry the vasodilatory agent and that NO release is dependent upon the differential reactivity of nitrite with hemoglobin in the oxygenated and deoxygenated state, rather than on an oxygen-dependent conformational change that affects the reactivity of hemoglobin bound S-nitrosothiol. There are many unanswered questions in the nitrite/hemoglobin story.

    The complex mechanisms of reaction are not fully understood, even in simple chemical systems devoid of the complexity of oxygen gradients, allosteric effectors and additional cellular constituents. Until these mechanisms have been established several puzzles will remain – the major one being that if NO is made by hemoglobin how does it escape the huge NO scavenging potential of the interior of the red cell? However, the physiological in vitro and in vivo studies all point to the fact that this interaction generates a diffusible vasodilator that may have a crucial role in the physiology and pathology of hypoxia.

    The reaction between nitrite and hemoglobin: the role of nitrite in hemoglobin-mediated hypoxic vasodilation. - PubMed - NCBI

    Methemoglobin (British: methaemoglobin) (pronounced "met-hemoglobin") is a hemoglobin in the form of metalloprotein, in which the iron in the heme group is in the Fe3+ (ferric) state, not the Fe2+ (ferrous) of normal hemoglobin. Methemoglobin cannot bind oxygen, which means it cannot carry oxygen to tissues. It is bluish chocolate-brown in color. In human blood a trace amount of methemoglobin is normally produced spontaneously, but when present in excess the blood becomes abnormally dark bluish brown. The NADH-dependent enzyme methemoglobin reductase (a type of diaphorase) is responsible for converting methemoglobin back to hemoglobin.

    Normally one to two percent of a person's hemoglobin is methemoglobin; a higher percentage than this can be genetic or caused by exposure to various chemicals and depending on the level can cause health problems known as methemoglobinemia. A higher level of methemoglobin will tend to cause a pulse oximeter to read closer to 85% regardless of the true level of oxygen saturation. An abnormal increase of methemoglobin will increase the oxygen binding affinity of normal hemoglobin, resulting in a decreased unloading of oxygen to the tissues. [2]

    Methemoglobin - Wikipedia


    Oxyhemoglobin is the normal, oxygen-carrying form of hemoglobin in which iron is in the reduced (ferrous) state. Methemoglobin is a nonfunctional form of hemoglobin in which ferrous iron is oxidized to ferric iron. Methemoglobin is nonfunctional because it cannot bind oxygen. In healthy animals, approximately 1% of oxyhemoglobin is converted to methemoglobin daily. Methemoglobin reductase reduces methemoglobin back to oxyhemoglobin. Rarely, methemoglobin reductase deficiency occurs as a congenital defect in dogs and produces significant methemoglobinemia and cyanosis. The oxyhemoglobin method for hemoglobin concentration measures only oxyhemoglobin, whereas the usual cyanmethemoglobin method measures all types of hemoglobin, including methemoglobin.

    Oxyhemoglobin - an overview | ScienceDirect Topics

    “… Making hemoglobin unable to carry oxygen, the nitrates do that even when we make internally from proteins under stress.“ Ray Peat

    “Polyunsaturated fats and their breakdown products--aldehydes, prostaglandins, isoprostanes, hydrocarbons, and free radicals--and carbon monoxide, nitric oxide, nitrite, and hydrogen peroxide are increased in the breath by most stresses” Ray Peat

    The research examined levels of nitrogen dioxide, a pollutant produced mostly by diesel vehicles, and weather conditions that can prevent dirty air from dispersing away from a city. Many studies have linked NO2 exposure to health damage, and particularly lung disease, which could make people more likely to die if they contract Covid-19.

    Air pollution may be ‘key contributor’ to Covid-19 deaths – study

    Nitrate and Methemoglobinemia

    Drinking water with high nitrate can cause a potentially fatal disorder called methemoglobinemia.

    Methemoglobinemia is a condition in which more than one percent of the hemoglobin in red blood cells take the form of methemoglobin. Hemoglobin carries oxygen in our blood, delivering it from the lungs to the rest of our body. Methemoglobin does not carry oxygen well and, when it replaces hemoglobin, it can cause a grayblueness of the skin (cyanosis).

    We have a lot of information about how excess nitrate in drinking water behaves in our bodies and leads to methemoglobinemia. Nitrate in water is almost completely absorbed into the blood. Our bodies convert a portion of that nitrate into nitrite. Nitrite reacts with blood to create methemoglobin. The more methemoglobin in the blood, the worse that blood is at carrying oxygen where it is needed. Along with these changes in blood chemistry, a person suffering methemoglobinemia may also experience elevated resting heart rate, weakness, nausea, and in severe cases, death.

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  2. Terma

    Terma Member

    May 8, 2017
    This is good info and yeah I reconsidered eating arugula for nitrates awhile ago