Alternate and Additional Functions of Erythrocyte Hemoglobin

Kosmachevskaya, O. V.; Топунов, А. Ф.

doi:10.1134/s0006297918120155

Cited by 27 publications

(26 citation statements)

References 140 publications

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“…The structural studies provided a plethora of data that offered glimpses of the magnificent molecular mechanisms behind Hb physiological functions. Hemoglobin is a polyfunctional molecule that is involved in several functions, such as catalytic (nitrite reductase, NO dioxygenase, monooxygenase, alkylhydroperoxidase, esterase, lipoxygenase); nitric oxide metabolism; metabolic reprogramming; pH regulation and maintaining redox balance (Kosmachevskaya and Topunov 2018). This chapter however, focuses on Hb primary function of oxygen transport and how mutations, endogenous or exogenous ligands or effectors affect Hb allostery.…”

Section: Introductionmentioning

confidence: 99%

Hemoglobin: Structure, Function and Allostery

Ahmed

Ghatge

Safo

2020

Subcellular Biochemistry

172

141

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This chapter reviews how allosteric (heterotrophic) effectors and natural mutations impact hemoglobin (Hb) primary physiological function of oxygen binding and transport. First, an introduction about the structure of Hb is provided, including the ensemble of tense and relaxed Hb states and the dynamic equilibrium of Hb multistate. This is followed by a brief review of Hb variants with altered Hb structure and oxygen binding properties. Finally, a review of different endogenous and exogenous allosteric effectors of Hb is presented with particular emphasis on the atomic interactions of synthetic ligands with altered allosteric function of Hb that could potentially be harnessed for the treatment of diseases.

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Section: Introductionmentioning

confidence: 99%

Hemoglobin: Structure, Function and Allostery

Ahmed

Ghatge

Safo

2020

Subcellular Biochemistry

172

141

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“…Finally, as judged by ALT and AST assays, V7 counteracts TB drug-induced hepatotoxicity - an important factor that affects negatively compliance and success of TB chemotherapy [27]. We are not sure why bilirubin has not followed the same trend as ALT and AST, but this perhaps is due to disparate pathways between hemoglobin-driven, catabolic production of bilirubin and subsequent processing by liver [28].…”

Section: Discussionmentioning

confidence: 99%

Phase III, placebo-controlled, randomized, double-blind trial of tableted, therapeutic TB vaccine (V7) containing heat-killed M. vaccae administered daily for one month

Bourinbaiar

Batbold²,

Efremenko³

et al. 2020

Journal of Clinical Tuberculosis and Other Mycobacterial Diseas

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ObjectiveImmunotherapy of tuberculosis (TB) to shorten treatment duration represents an unmet medical need. Orally delivered, tableted TB vaccine (V7) containing heat-killed Mycobacterium vaccae (NCTC 11659) has been demonstrated in prior clinical studies to be safe and fast-acting immune adjunct.MethodsThe outcome of Phase III trial of V7 containing 10 µg of hydrolyzed M. vaccae was evaluated in 152 patients randomized at 2:1 ratio: V7 (N = 100), placebo (N = 52). Both arms received conventional 1st or 2nd line TB drugs co-administered with daily pill of V7 or placebo.ResultsAfter one month mycobacterial clearance was observed in 68% (P < 0.0001) and 23.1% (P = 0.04) of patients on V7 and placebo. Stratified conversion rates in V7 recipients with drug-sensitive and multidrug-resistant TB were 86.7% and 55.6% vs 27.2% and 15% in placebo. Patients on V7 gained on average 2.4 kg (P < 0.0001) vs 0.3 kg (P = 0.18) in placebo. Improvements in hemoglobin levels, erythrocyte sedimentation rate and leukocyte counts were significantly better than in controls. Liver function tests revealed that V7 can prevent chemotherapy-induced hepatic damage.ConclusionOral M. vaccae is safe, can overcome TB-associated weight loss and inflammation, reduce hepatotoxicity of TB drugs, improve sputum conversion three-fold OR 3.15; 95%CI (2.3,4.6), and cut treatment length by at least six-fold. Longer follow-up studies might be needed to further substantiate our findings (Clinicaltrials.gov: NCT01977768).

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“…•− and NO concentrations in RBCs [163]. Moreover, under the reduced oxygen concentration, the intensity of glycolysis increases, which is accompanied by a rise in MG production [164].…”

Section: Relationship Of Carbonyl Stress With Oxidative and Nitrosatimentioning

confidence: 98%

Carbonyl Stress in Red Blood Cells and Hemoglobin

2021

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The paper overviews the peculiarities of carbonyl stress in nucleus-free mammal red blood cells (RBCs). Some functional features of RBCs make them exceptionally susceptible to reactive carbonyl compounds (RCC) from both blood plasma and the intracellular environment. In the first case, these compounds arise from the increased concentrations of glucose or ketone bodies in blood plasma, and in the second—from a misbalance in the glycolysis regulation. RBCs are normally exposed to RCC—methylglyoxal (MG), triglycerides—in blood plasma of diabetes patients. MG modifies lipoproteins and membrane proteins of RBCs and endothelial cells both on its own and with reactive oxygen species (ROS). Together, these phenomena may lead to arterial hypertension, atherosclerosis, hemolytic anemia, vascular occlusion, local ischemia, and hypercoagulation phenotype formation. ROS, reactive nitrogen species (RNS), and RCC might also damage hemoglobin (Hb), the most common protein in the RBC cytoplasm. It was Hb with which non-enzymatic glycation was first shown in living systems under physiological conditions. Glycated HbA1c is used as a very reliable and useful diagnostic marker. Studying the impacts of MG, ROS, and RNS on the physiological state of RBCs and Hb is of undisputed importance for basic and applied science.

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Alternate and Additional Functions of Erythrocyte Hemoglobin

Cited by 27 publications

References 140 publications

Hemoglobin: Structure, Function and Allostery

Hemoglobin: Structure, Function and Allostery

Phase III, placebo-controlled, randomized, double-blind trial of tableted, therapeutic TB vaccine (V7) containing heat-killed M. vaccae administered daily for one month

Carbonyl Stress in Red Blood Cells and Hemoglobin

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