Chronic diseases are responsible for 7 in 10 deaths each year, and treating people with chronic diseases accounts for most of our nation’s health care costs. We know that many chronic diseases can be prevented by eating well, being physically active, avoiding tobacco and excessive drinking, and getting regular health screenings. CDC’s National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP) helps people and communities prevent chronic disease and promotes health and wellness for all. National Center for Chronic Disease Prevention and Health Promotion

National Center For Chronic Disease Prevention and Health Promotion regions

Carbon monoxide (CO) is the leading cause of poisoning deaths in many countries, including Japan. Annually, CO poisoning claims about 2000-5000 lives in Japan, which is over half of the total number of poisoning deaths. This paper discusses the physicochemical properties of CO and the toxicological evaluation of CO poisoning.

Carbon monoxide poisoning.

This book focuses on respiratory proteins, the broad hemoglobin family, as well as the molluscan and arachnid hemocyanins (and their multifunctional roles). Featuring 20 chapters addressing invertebrate and vertebrate respiratory proteins, lipoproteins and other body fluid proteins, and drawing on the editors' extensive research in the field, it is a valuable addition to the Subcellular Biochemistry book series. The book covers a wide range of topics, including lipoprotein structure and lipid transport; diverse annelid, crustacean and insect defense proteins; and insect and vertebrate immune complexes. It also discusses a number of other proteins, such as the hemerythrins; serum albumin; serum amyloid A; von Willebrand factor and its interaction with factor VIII; and C-reactive protein. Given its scope, the book appeals to biologists, biomedical scientists and clinicians, as well as advanced undergraduates and postgraduates in these disciplines. Available as a printed book and also as an e-book and e-chapters, the fascinating material included is easily accessible.

Vertebrate and invertebrate respiratory proteins, lipoproteins and other body fluid proteins

Native mass spectrometry involves transferring large biomolecular complexes into the gas phase, enabling the characterization of their composition and stoichiometry. However, the overlap in distributions created by residual solvation, ionic adducts, and post-translational modifications creates a high degree of complexity that typically goes unresolved at masses above ∼150 kDa. Therefore, native mass spectrometry would greatly benefit from higher resolution approaches for intact proteins and their complexes. By recording mass spectra of individual ions via charge detection mass spectrometry, we report isotopic resolution for pyruvate kinase (232 kDa) and β-galactosidase (466 kDa), extending the limits of isotopic resolution for high mass and high m/z by >2.5-fold and >1.6-fold, respectively.

Isotopic Resolution of Protein Complexes up to 466 kDa Using Individual Ion Mass Spectrometry.

The benzene metabolite p-benzoquinone inhibits the catalytic activity of bovine liver catalase: A biophysical study

Cigarette smoke (CS) is an important source of morbidity and early mortality worldwide. Besides causing various life-threatening diseases, CS is also known to cause hypoxia. Chronic hypoxia would induce early aging and premature death. Continuation of smoking during pregnancy is a known risk for the unborn child. Although carbon monoxide (CO) is considered to be a cause of hypoxia, the effect of other component(s) of CS on hypoxia is not known. Here we show by immunoblots and mass spectra analyses that in smoker’s blood p -benzoquinone ( p -BQ) derived from CS forms covalent adducts with cysteine 93 residues in both the β chains of hemoglobin (Hb) producing Hb- p -BQ adducts. UV–vis spectra and CD spectra analyses show that upon complexation with p -BQ the structure of Hb is altered. Compared to nonsmoker’s Hb, the content of α-helix decreased significantly in smoker’s Hb ( p  = 0.0224). p -BQ also induces aggregation of smoker’s Hb as demonstrated by SDS-PAGE, dynamic light scattering and atomic force microscopy. Alteration of Hb structure in smoker’s blood is accompanied by reduced oxygen binding capacity. Our results provide the first proof that p -BQ is a cause of hypoxia in smokers. We also show that although both p -BQ and CO are responsible for causing hypoxia in smokers, exposure to CO further affects the function over and above that produced by Hb- p -BQ adduct.

Interaction of p-benzoquinone with hemoglobin in smoker's blood causes alteration of structure and loss of oxygen binding capacity.

Application of isotope exchange based mass spectrometry to understand the mechanism of inhibition of sickle hemoglobin polymerization upon oxygenation

Sickle cell hemoglobin (HbS) is an example of a genetic variant of human hemoglobin where a point mutation in the β globin gene results in substitution of glutamic acid to valine at sixth position of the β globin chain. Association between tetrameric hemoglobin molecules through noncovalent interactions between side chain residue of βVal6 and hydrophobic grooves formed by βAla70, βPhe85 and βLeu88 amino acid residues of another tetramer followed by the precipitation of the elongated polymer leads to the formation of sickle-shaped RBCs in the deoxygenated state of HbS. There are multiple non-covalent interactions between residues across intra- and inter-strands that stabilize the polymer. The clinical phenotype of sickling of RBCs manifests as sickle cell anemia, which was first documented in the year 1910 in an African patient. Although the molecular reason of the disease has been understood well over the decades of research and several treatment procedures have been explored to date, an effective therapeutic strategy for sickle cell anemia has not been discovered yet. Surprisingly, it has been observed that the oxy form of HbS and glutathionylated form of deoxy HbS inhibits polymerization. In addition to describe the residue level interactions in the HbS polymer that provides its stability, here we explain the mechanism of inhibition in the polymerization of HbS in its oxy state. Additionally, we reported the molecular insights of inhibition in the polymerization for glutathionyl HbS, a posttranslational modification of hemoglobin, even in its deoxy state. In this chapter we briefly consider the available treatment procedures of sickle cell anemia and propose that the elevation of glutathionylation of HbS within RBCs, without inducing oxidative stress, might be an effective therapeutic strategy for sickle cell anemia.

Sickle Cell Hemoglobin.

Structural analysis of glutathionyl hemoglobin using native mass spectrometry.

https://link.springer.com/content/pdf/10.1007%2Fs13361-018-2011-1.pdf

Amrita Mitra

Papers

Interaction of p-benzoquinone with hemoglobin in smoker's blood causes alteration of structure and loss of oxygen binding capacity.

Application of isotope exchange based mass spectrometry to understand the mechanism of inhibition of sickle hemoglobin polymerization upon oxygenation

Sickle Cell Hemoglobin.

Structural analysis of glutathionyl hemoglobin using native mass spectrometry.

Conjugation of para-benzoquinone of Cigarette Smoke with Human Hemoglobin Leads to Unstable Tetramer and Reduced Cooperative Oxygen Binding