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Biochemistry, Genetics and Molecular Biology › Cell Biology

Hemoglobin structure and function

Works Count: 55587

Description

This cluster of papers focuses on the function, regulation, and physiological impact of hemoglobin and related proteins in vertebrates. It covers topics such as scavenger receptor CD163 expression, neuroglobin and myoglobin function, haptoglobin phenotype, nitric oxide dioxygenase activity, and the role of flavohemoglobins in detoxifying nitric oxide. The papers also discuss the use of hemoglobin-based oxygen carriers and their potential impact on cardiovascular disease.

Keywords

Hemoglobin; Scavenger Receptor; Globin Family; Oxygen Carriers; Neuroglobin; CD163 Expression; Myoglobin Function; Haptoglobin Phenotype; Nitric Oxide Dioxygenase; Flavohemoglobin

4 Lactate Dehydrogenase

1975-01-01
J. John Holbrook , Anders Liljas , Steven J. Steindel +1 more

MICRODETERMINATION OF OXYHEMOGLOBIN, METHEMOGLOBIN, AND SULFHEMOGLOBIN IN A SINGLE SAMPLE OF BLOOD

1938-12-01
Kenneth A. Evelyn , Helga Tait Malloy

The interaction of a naphthalene dye with apomyoglobin and apohemoglobin

1965-09-01
Lubert Stryer

An enzymic method for the trace iodination of immunoglobulins and other proteins

1969-06-01
John J. Marchalonis
1. A method is described for the trace iodination of immunoglobulins and other serum proteins by a system consisting of lactoperoxidase, hydrogen peroxide and iodide. 2. γG immunoglobulin that had … 1. A method is described for the trace iodination of immunoglobulins and other serum proteins by a system consisting of lactoperoxidase, hydrogen peroxide and iodide. 2. γG immunoglobulin that had been labelled to a specific radioactivity of 5μc/μg. by use of carrier-free [125I]iodide gave no evidence of denaturation when analysed by electrophoresis and density-gradient ultracentrifugation. 3. Tryptic hydrolysis and peptide ‘mapping’ of a completely characterized peptide radioiodinated by this method showed that the [125I]iodide was bound to tyrosyl residues. 4. Proteins differ in their susceptibility to iodination by this method. Human γG immunoglobulin, for example, is iodinated more than ten times as readily as is human α2-macroglobulin under the same conditions. 5. Lactoperoxidase catalyses the iodination of proteins much more readily than does horseradish peroxidase.
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Evaluation of enzyme inhibitors in drug discovery. A guide for medicinal chemists and pharmacologists.

2005-01-01
Robert A. Copeland
Foreword. Preface. Acknowledgments. 1. Why Enzymes as Drug Targets? 1.1 Enzymes Are Essentials for Life. 1.2 Enzyme Structure and Catalysis. 1.3 Permutations of Enzyme Structure During Catalysis. 1.4 Other Reasons … Foreword. Preface. Acknowledgments. 1. Why Enzymes as Drug Targets? 1.1 Enzymes Are Essentials for Life. 1.2 Enzyme Structure and Catalysis. 1.3 Permutations of Enzyme Structure During Catalysis. 1.4 Other Reasons for Studying Enzymes. 1.5 Summary. References. 2. Enzyme Reaction Mechanisms. 2.1 Initial Binding of Substrate. 2.2 Noncovalent Forces in Reversible Ligand Binding to Enzymes. 2.2.1 Electrostatic Forces. 2.2.2 Hydrogen Bonds. 2.2.3 Hydrophobic Forces. 2.2.4 van der Waals Forces. 2.3 Transformations of the Bond Substrate. 2.3.1 Strategies for Transition State Stabilization. 2.3.2 Enzyme Active Sites Are Most Complementary to the Transition State Structure. 2.4 Steady State Analysis of Enzyme Kinetics. 2.4.1 Factors Affecting the Steady State Kinetic Constants. 2.5 Graphical Determination of k cat and K M 2.6 Reactions Involving Multiple Substates. 2.6.1 Bisubstrate Reaction Mechanisms. 2.7 Summary. References. 3. Reversible Modes of Inhibitor Interactions with Enzymes. 3.1 Enzyme-Inhibitor Binding Equilibria. 3.2 Competitive Inhibition. 3.3 Noncompetitive Inhibition. 3.3.1 Mutual Exclusively Studies. 3.4 Uncompetitive Inhibition. 3.5 Inhibition Modality in Bisubstrate Reactions. 3.6 Value of Knowing Inhibitor Modality. 3.6.1 Quantitative Comparisons of Inhibitor Affinity. 3.6.2 Relating K i to Binding Energy. 3.6.3 Defining Target Selectivity by K i Values. 3.6.4 Potential Advantages and Disadvantages of Different Inhibition Modalities In Vivo. 3.6.5 Knowing Inhibition Modality Is Important for Structure-Based Lead Organization. 3.7 Summary. References. 4. Assay Considerations for Compound Library Screening. 4.1 Defining Inhibition Signal Robustness, and Hit Criteria. 4.2 Measuring Initial Velocity. 4.2.1 End-Point and Kinetic Readouts. 4.2.2 Effects of Enzyme Concentration. 4.3 Balanced Assay Conditions. 4.3.1 Balancing Conditions for Multisubstrate Reactions. 4.4 Order of Reagent Addition. 4.5 Use of Natural Substrates and Enzymes. 4.6 Coupled Enzyme Assays. 4.7 Hit Validation and Progression. 4.8 Summary. References. 5. Lead Optimization and Structure-Activity Relationships for Reversible Inhibitors. 5.1 Concentration-Response Plots and IC 50 Determination. 5.1.1 The Hill Coefficient. 5.1.2 Graphing and Reporting Concentration-Response Data. 5.2 Testing for Reversibility. 5.3 Determining Reversible Inhibition Modality and Dissociation Constant. 5.4 Comparing Relative Affinity. 5.4.1 Compound Selectivity. 5.5 Associating Cellular Effects with Target Enzyme Inhibition. 5.5.1 Cellular Phenotype Should Be Consistent with Genetic Knockout or Knockdown of the Target Enzyme. 5.5.2 Cellular Activity Should Require a Certain Affinity for the target Enzyme. 5.5.3 Buildup of Substrate and/or Diminution of Product for the Target Enzyme Should Be Observed in Cells. 5.5.4 Cellular Phenotype Should Be Reversed by Cell-Permeable Product or Downstream Metabolites of the Target Enzyme Activity. 5.5.5 Mutation of the Target Enzyme Should Lead to Resistance or Hypersensitivity to Inhibitors. 5.6 Summary. References. 6. Slow Binding Inhibitors. 6.1 Determining k obs : The Rate Constant for Onset of Inhibition. 6.2 Mechanisms of Slow Binding Inhibition. 6.3 Determination of Mechanism and Assessment of True Affinity. 6.3.1 Potential Clinical Advantages of Slow Off-rate Inhibitors. 6.4 Determining Inhibition Modality for Slow Binding Inhibitors. 6.5 SAR for Slow Binding Inhibitors. 6.6 Some Examples of Pharmacologically Interesting Slow Binding Inhibitors. 6.6.1 Examples of Scheme B: Inhibitors of Zinc Peptidases and Proteases. 6.6.2 Example of Scheme C: Inhibition of Dihydrofolate Reductase by Methotresate. 6.6.3 Example of Scheme C: Inhibition of Calcineurin by FKBP-Inhibitor Complexes. 6.6.4 Example of Scheme C When K i << K i : Aspartyl Protease Inhibitors. 6.6.5 Example of Scheme C When k 6 Is Very Small: Selective COX2 Inhibitors. 6.7 Summary. References. 7. Tight Binding Inhibitors. 7.1 Effects of Tight Binding Inhibition Concentration-Response Data. 7.2 The IC 50 Value Depends on K i app and [E] T . 7.3 Morrison's Quadratic Equation for Fiting Concentration-Response Data for Tight Binding Inhibitors. 7.3.1 Optimizing Conditions for K i app Determination Using Morrison's Equation. 7.3.2 Limits on K i app Determinations. 7.3.3 Use of a Cubic Equation When Both Substrate and Inhibitor Are Tight Binding. 7.4 Determining Modality for Tight Binding Enzyme Inhibitors. 7.5 Tight Binding Inhibitors Often Display Slow Binding Behavior. 7.6 Practical Approaches to Overcoming the Tight Binding Limit in Determine K i . 7.7 Enzyme-Reaction Intermediate Analogues as Example of Tight Binding Inhibitors. 7.7.1 Bisubstrate Analogues. 7.7.2 Testing for Transition State Mimicry. 7.8 Potential Clinical Advantages of Tight Binding Inhibitors. 7.9 Determination of [E] T Using Tight Binding Inhibitors. 7.10 Summary. References. 8. Irreversible Enzyme Inactivators. 8.1 Kinetic Evaluation of Irreversible Enzyme Inactivators. 8.2 Affinity Labels. 8.2.1 Quiescent Affinity Labels. 8.2.2 Potential Liabilities of Affinity Labels as Drugs. 8.3 Mechanism-Based Inactivators. 8.3.1 Distinguishing Features of Mechanism-Based Inactivation. 8.3.2 Determination of the Partition Ratio. 8.3.3 Potential Clinical Advantages of Mechanism-Based Inactivators. 8.3.4 Examples of Mechanism-Based Inactivators as Drugs. 8.4 Use of Affinity Labels as Mechanistic Tools. 8.5 Summary. References. Appendix 1. Kinetic of Biochemical Reactions. A1.1 The Law of Mass Action and Reaction Order. A1.2 First-Order Reaction Kinetics. A1.3 Second-Order Reaction Kinetics. A1.4 Pseudo-First-Order Reaction Conditions. A1.5 Approach to Equilibrium: An Example of the Kinetics of Reversible Reactions. References. Appendix 2. Derivation of the Enzyme-Ligand Binding Isotherm Equation. References. Appendix 3. Serial Dilution Schemes. Index.

[49] Determination of carbonyl content in oxidatively modified proteins

1990-01-01
Rodney L. Levine , Donita Garland , Cynthia N. Oliver +6 more

The Generation of Superoxide Radical during the Autoxidation of Hemoglobin

1972-11-01
Hara P. Misra , Irwin Fridovich
The autoxidation of oxyhemoglobin to methemoglobin, at pH 6.8, causes the co-oxidation of epinephrine to adrenochrome. Part of this co-oxidation was due to a hemoglobincatalyzed peroxidation of epinephrine and could … The autoxidation of oxyhemoglobin to methemoglobin, at pH 6.8, causes the co-oxidation of epinephrine to adrenochrome. Part of this co-oxidation was due to a hemoglobincatalyzed peroxidation of epinephrine and could be inhibited by catalase. The remainder of the co-oxidation of epinephrine was inhibited by superoxide dismutase. This indicates that the autoxidation of oxyhemoglobin results in the generation of superoxide radicals.

Small-Angle X-Ray Scattering

2016-01-01
Bharat Bhushan

[1] Measurement of molecular weights by electrophoresis on SDS-acrylamide gel

1972-01-01
K Weber , John R. Pringle , Mary Osborn

A Linear Steady-State Treatment of Enzymatic Chains. General Properties, Control and Effector Strength

1974-02-01
Reinhart Heinrich , Tom A. Rapoport
A theoretical analysis of linear enzymatic chains is presented. By linear approximation simple analytical solutions can be obtained for the metabolite concentrations and the flux through the chain for steady-state … A theoretical analysis of linear enzymatic chains is presented. By linear approximation simple analytical solutions can be obtained for the metabolite concentrations and the flux through the chain for steady-state conditions. The equations are greatly simplified if the common kinetic constants are expressed as functions of two parameters, i.e. the thermodynamic equilibrium constant and the "characteristic time". Three cardinal terms are proposed for the quantitative description of enzyme systems. The first two are the control strength and the control matrix; these indicate the dependence of the flux and the metabolite concentrations, respectively, on the kinetic properties of a given enzyme. The third is the effector strength, which defines the dependence of the velocity of an enzyme on the concentration of an effector; it expresses the importance of an effector. By linear approximation simple analytical expressions were derived for the control strength, the control matrix and the mass-action ratios. The effector strength was calculated for two cases: for a competitive inhibitor and for allosteric effectors according to the Monod (1965) model. The influence of an effector on the concentrations of the metabolites was considered.
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A vertebrate globin expressed in the brain

2000-09-01
Thorsten Burmester , Bettina Weich , Sigrid Reinhardt +1 more

Plasma Instabilities and Nonlinear Effects

1975-01-01
Akira Hasegawa

Biological and clinical significance of haptoglobin polymorphism in humans

1996-10-01
Michel R. Langlois , Joris R. Delanghe
Haptoglobin is a hemoglobin-binding protein expressed by a genetic polymorphism as three major phenotypes: 1-1, 2-1, and 2-2. Most attention has been paid to determining haptoglobin phenotype as a genetic … Haptoglobin is a hemoglobin-binding protein expressed by a genetic polymorphism as three major phenotypes: 1-1, 2-1, and 2-2. Most attention has been paid to determining haptoglobin phenotype as a genetic fingerprint used in forensic medicine. More recently, several functional differences between haptoglobin phenotypes have been demonstrated that appear to have important biological and clinical consequences. Haptoglobin polymorphism is associated with the prevalence and clinical evolution of many inflammatory diseases, including infections, atherosclerosis, and autoimmune disorders. These effects are explained by a phenotype-dependent modulation of oxidative stress and prostaglandin synthesis. Recent evidence is growing that haptoglobin is involved in the immune response as well. The strong genetic pressure favoring the 2-2 phenotype suggests an important role of haptoglobin in human pathology.
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An Enzyme Cascade in the Blood Clotting Mechanism, and its Function as a Biochemical Amplifier

1964-05-01
Robert Macfarlane

The helical hydrophobic moment: a measure of the amphiphilicity of a helix

1982-09-01
David Eisenberg , Robert M. Weiss , Thomas C. Terwilliger

Determination of Intracellular pH by 31P Magnetic Resonance

1973-10-01
Richard B. Moon , John H. Richards
Observation of the ^(31)P signal from various intracellular phosphates can provide a convenient, nondestructive technique for determining intracellular conditions such as pH. This procedure has been explored with particular reference … Observation of the ^(31)P signal from various intracellular phosphates can provide a convenient, nondestructive technique for determining intracellular conditions such as pH. This procedure has been explored with particular reference to the erythrocyte. Both the chemical shift of intracellular inorganic phosphate relative to that of serum phosphate and the positions of, and more especially the difference between, the chemical shifts of 2,3-diphosphoglycerate have been used to monitor intracellular pH of erythrocytes whose hemoglobin has been liganded with carbon monoxide.

Temperature-dependent X-ray diffraction as a probe of protein structural dynamics

1979-08-01
Hans Frauenfelder , Gregory A. Petsko , Demetrius Tsernoglou

Principles of structure, bonding, and reactivity for metal nitrosyl complexes

1974-09-01
John H. Enemark , Robert D. Feltham

Regulation of the Erythropoietin Gene: Evidence That the Oxygen Sensor Is a Heme Protein

1988-12-09
Mark A. Goldberg , Susan P. Dunning , H. Franklin Bunn
Erythropoietin (Epo), the hormone that stimulates red blood cell production, is synthesized in the kidney and liver in response to hypoxia. The human hepatoma cell line Hep3B regulates its production … Erythropoietin (Epo), the hormone that stimulates red blood cell production, is synthesized in the kidney and liver in response to hypoxia. The human hepatoma cell line Hep3B regulates its production of Epo in a physiologic manner. Either hypoxia or cobalt chloride markedly increases expression of Epo mRNA as well as production of biologically active and immunologically distinct Epo protein. New protein synthesis is required before the induction of increased levels of hypoxia- or cobalt-induced Epo mRNA. Hypoxia, cobalt chloride, and nickel chloride appear to stimulate Epo production through a common pathway. The inhibition of Epo production at low partial pressures of oxygen by carbon monoxide provides evidence that a heme protein is integrally involved in the oxygen-sensing mechanism. This hypothesis is further supported by the finding that when heme synthesis is blocked, hypoxia-, cobalt-, and nickel-induced Epo production are all markedly inhibited. A model is proposed in which a ligand-dependent conformational change in a heme protein accounts for the mechanism by which hypoxia as well as cobalt and nickel stimulate the production of Epo.

Synthetic oxygen carriers related to biological systems

1979-04-01
Robert Jones , David A. Summerville , Fred Basolo
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic oxygen carriers related to biological systemsRobert D. Jones, David A. Summerville, and Fred. BasoloCite this: Chem. Rev. 1979, 79, 2, 139–179Publication Date (Print):April 1, 1979Publication History … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic oxygen carriers related to biological systemsRobert D. Jones, David A. Summerville, and Fred. BasoloCite this: Chem. Rev. 1979, 79, 2, 139–179Publication Date (Print):April 1, 1979Publication History Published online1 May 2002Published inissue 1 April 1979https://pubs.acs.org/doi/10.1021/cr60318a002https://doi.org/10.1021/cr60318a002research-articleACS PublicationsRequest reuse permissionsArticle Views4343Altmetric-Citations945LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Probing Structure-Function Relations in Heme-Containing Oxygenases and Peroxidases

1988-04-22
John H. Dawson
Structural factors that influence functional properties are examined in the case of four heme enzymes: cytochrome P-450, chloroperoxidase, horseradish peroxidase, and secondary amine mono-oxygenase. The identity of the axial ligand, … Structural factors that influence functional properties are examined in the case of four heme enzymes: cytochrome P-450, chloroperoxidase, horseradish peroxidase, and secondary amine mono-oxygenase. The identity of the axial ligand, the nature of the heme environment, and the steric accessibility of the heme iron and heme edge combine to play major roles in determining the reactivity of each enzyme. The importance of synthetic porphyrin models in understanding the properties of the protein-free metal center is emphasized. The conclusions described herein have been derived from studies at the interface between biological and inorganic chemistry.

Structure of Myoglobin: A Three-Dimensional Fourier Synthesis at 2 Å. Resolution

1960-02-01
J Kendrew , Richard E. Dickerson , B. Strandberg +4 more

Standardization of hemoglobinometry II. The hemiglobincyanide method

1961-07-01
Erik-Jan Van Kampen , W. G. Zijlstra

Cleavage of the haem-protein link by acid methylethylketone

1959-01-01
F. W. J. Teale

The Magnetic Properties and Structure of Hemoglobin, Oxyhemoglobin and Carbonmonoxyhemoglobin

1936-04-01
Linus Pauling , Charles D. Coryell
Over ninety years ago, on November 8, 1845, Michael Faraday investigated the magnetic properties of dried blood and made a note “Must try recent fluid blood.” If he had determined … Over ninety years ago, on November 8, 1845, Michael Faraday investigated the magnetic properties of dried blood and made a note “Must try recent fluid blood.” If he had determined the magnetic susceptibilities of arterial and venous blood, he would have found them to differ by a large amount (as much as twenty per cent for completely oxygenated and completely deoxygenated blood); this discovery without doubt would have excited much interest and would have influenced appreciably the course of research on blood and hemoglobin.1 Continuing our investigations of the magnetic properties and structure of hemoglobin and related substances,2 we have found oxyhemoglobin and carbonmonoxyhemoglobin to contain no unpaired electrons, and ferrohemoglobin (hemoglobin itself) to contain four unpaired electrons per heme. The description of our experiments and the interpretation and discussion of the results are given below. The current nomenclature of hemoglobin and related substances was formulated at a time when precise information about the chemical composition and structure of the substances was not available. Now that some progress has been made in gathering this information, especially in regard to chemical composition, it is possible to revise the nomenclature in such a way as to make the names of substances more descriptive than the older names, without introducing any radical changes. In formulating the following set of names we have profited by the continued advice of Dr. Alfred E. Mirsky. The names whose use we advocate are given below, followed in some cases by acceptable synonyms. The expressions in parentheses are those whose use we consider to be undesirable.Heme: an iron-porphyrin complex (generic term, used for either ferroheme or ferriheme).Ferroheme (reduced heme): a complex of ferrous iron and a porphyrin.Ferriheme (oxidized heme): a complex of ferric iron and a porphyrin.Ferriheme chloride, …
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An improved staining procedure for the detection of the peroxidase activity of cytochrome P-450 on sodium dodecyl sulfate polyacrylamide gels

1976-09-01
Paul E. Thomas , Dene E. Ryan , Wayne Levin

Stereochemistry of Cooperative Effects in Haemoglobin: Haem–Haem Interaction and the Problem of Allostery

1970-11-01
M. F. Perutz

Size and charge isomer separation and estimation of molecular weights of proteins by disc gel electrophoresis

1968-07-01
Jerry L. Hedrick , Alan Jay Smith

The lipocalin protein family: structure and function

1996-08-15
Darren R. Flower
The lipocalin protein family is a large group of small extracellular proteins. The family demonstrates great diversity at the sequence level; however, most lipocalins share three characteristic conserved sequence motifs, … The lipocalin protein family is a large group of small extracellular proteins. The family demonstrates great diversity at the sequence level; however, most lipocalins share three characteristic conserved sequence motifs, the kernel lipocalins, while a group of more divergent family members, the outlier lipocalins, share only one. Belying this sequence dissimilarity, lipocalin crystal structures are highly conserved and comprise a single eight-stranded continuously hydrogen-bonded antiparallel β-barrel, which encloses an internal ligand-binding site. Together with two other families of ligand-binding proteins, the fatty-acid-binding proteins (FABPs) and the avidins, the lipocalins form part of an overall structural superfamily: the calycins. Members of the lipocalin family are characterized by several common molecular-recognition properties: the ability to bind a range of small hydrophobic molecules, binding to specific cell-surface receptors and the formation of complexes with soluble macromolecules. The varied biological functions of the lipocalins are mediated by one or more of these properties. In the past, the lipocalins have been classified as transport proteins; however, it is now clear that the lipocalins exhibit great functional diversity, with roles in retinol transport, invertebrate cryptic coloration, olfaction and pheromone transport, and prostaglandin synthesis. The lipocalins have also been implicated in the regulation of cell homoeostasis and the modulation of the immune response, and, as carrier proteins, to act in the general clearance of endogenous and exogenous compounds.
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Dynamics of ligand binding to myoglobin

1975-12-01
Robert H. Austin , K. W. Beeson , L. Eisenstein +2 more
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDynamics of ligand binding to myoglobinR. H. Austin, K. W. Beeson, L. Eisenstein, H. Frauenfelder, and I. C. GunsalusCite this: Biochemistry 1975, 14, 24, 5355–5373Publication Date (Print):December … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDynamics of ligand binding to myoglobinR. H. Austin, K. W. Beeson, L. Eisenstein, H. Frauenfelder, and I. C. GunsalusCite this: Biochemistry 1975, 14, 24, 5355–5373Publication Date (Print):December 1, 1975Publication History Published online1 May 2002Published inissue 1 December 1975https://pubs.acs.org/doi/10.1021/bi00695a021https://doi.org/10.1021/bi00695a021research-articleACS PublicationsRequest reuse permissionsArticle Views3601Altmetric-Citations1304LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Life in moving fluids: the physical biology of flow

1995-04-01
Steven Vogel
Both a landmark text and reference book, Steven Vogel's Life in Moving Fluids has also played a catalytic role in research involving the applications of fluid mechanics to biology. In … Both a landmark text and reference book, Steven Vogel's Life in Moving Fluids has also played a catalytic role in research involving the applications of fluid mechanics to biology. In this revised edition, Vogel continues to combine humor and clear explanations as he addresses biologists and general readers interested in biological fluid mechanics, offering updates on the field over the last dozen years and expanding the coverage of the biological literature. His discussion of the relationship between fluid flow and biological design now includes sections on jet propulsion, biological pumps, swimming, blood flow, and surface waves, and on acceleration reaction and Murray's law. This edition contains an extensive bibliography for readers interested in designing their own experiments.
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Quantitative approach to biochemical structure-activity relationships

1969-08-01
Corwin Hansch
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTQuantitative approach to biochemical structure-activity relationshipsCorwin HanschCite this: Acc. Chem. Res. 1969, 2, 8, 232–239Publication Date (Print):August 1, 1969Publication History Published online1 May 2002Published inissue 1 August … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTQuantitative approach to biochemical structure-activity relationshipsCorwin HanschCite this: Acc. Chem. Res. 1969, 2, 8, 232–239Publication Date (Print):August 1, 1969Publication History Published online1 May 2002Published inissue 1 August 1969https://pubs.acs.org/doi/10.1021/ar50020a002https://doi.org/10.1021/ar50020a002research-articleACS PublicationsRequest reuse permissionsArticle Views1844Altmetric-Citations765LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Preservation of Membranes in Anhydrobiotic Organisms: The Role of Trehalose

1984-02-17
John H. Crowe , Lois M. Crowe , D. Chapman
Trehalose is a nonreducing disaccharide of glucose commonly found at high concentrations in anhydrobiotic organisms. In the presence of trehalose, dry dipalmitoyl phosphatidylcholine (DPPC) had a transition temperature similar to … Trehalose is a nonreducing disaccharide of glucose commonly found at high concentrations in anhydrobiotic organisms. In the presence of trehalose, dry dipalmitoyl phosphatidylcholine (DPPC) had a transition temperature similar to that of the fully hydrated lipid, whereas DPPC dried without trehalose had a transition temperature about 30 degrees Kelvin higher. Results obtained with infrared spectroscopy indicate that trehalose and DPPC interact by hydrogen bonding between the OH groups in the carbohydrate and the polar head groups of DPPC. These and previous results show that this hydrogen bonding alters the spacing of the polar head groups and may thereby decrease van der Waals interactions in the hydrocarbon chains of the DPPC. This interaction between trehalose and DPPC is specific to trehalose. Hence this specificity may be an important factor in the ability of this molecule to stabilize dry membranes in anhydrobiotic organisms.

On the Absorption of Fluids from the Connective Tissue Spaces

1896-05-05
E. H. Starling

Three-dimensional Fourier Synthesis of Horse Oxyhaemoglobin at 2.8 Å Resolution: The Atomic Model

1968-07-01
M. F. Perutz , H. Muirhead , Joyce M. Cox +1 more

Dynamical transition of myoglobin revealed by inelastic neutron scattering

1989-02-01
W. Doster , S. Cusack , W. Petry

The chemical shift index: a fast and simple method for the assignment of protein secondary structure through NMR spectroscopy

1992-02-18
David S. Wishart , Brian D. Sykes , F.M. Richards
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe chemical shift index: a fast and simple method for the assignment of protein secondary structure through NMR spectroscopyD. S. Wishart, B. D. Sykes, and F. M. … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe chemical shift index: a fast and simple method for the assignment of protein secondary structure through NMR spectroscopyD. S. Wishart, B. D. Sykes, and F. M. RichardsCite this: Biochemistry 1992, 31, 6, 1647–1651Publication Date (Print):February 18, 1992Publication History Published online1 May 2002Published inissue 18 February 1992https://pubs.acs.org/doi/10.1021/bi00121a010https://doi.org/10.1021/bi00121a010research-articleACS PublicationsRequest reuse permissionsArticle Views7170Altmetric-Citations1723LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

The Energy Landscapes and Motions of Proteins

1991-12-13
Hans Frauenfelder , Stephen G. Sligar , Peter G. Wolynes
Recent experiments, advances in theory, and analogies to other complex systems such as glasses and spin glasses yield insight into protein dynamics. The basis of the understanding is the observation … Recent experiments, advances in theory, and analogies to other complex systems such as glasses and spin glasses yield insight into protein dynamics. The basis of the understanding is the observation that the energy landscape is complex: Proteins can assume a large number of nearly isoenergetic conformations (conformational substates). The concepts that emerge from studies of the conformational substates and the motions between them permit a quantitative discussion of one simple reaction, the binding of small ligands such as carbon monoxide to myoglobin.

S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control

1996-03-01
Lee Jia , Celia Bonaventura , Joseph Bonaventura +1 more

Conformational Substates in Proteins

1988-06-01
Hans Frauenfelder , F. Parak , Robert D. Young
Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems employ the dual RNA–guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific ...Read … Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems employ the dual RNA–guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific ...Read More

THE ULTRASTRUCTURAL BASIS OF CAPILLARY PERMEABILITY STUDIED WITH PEROXIDASE AS A TRACER

1967-10-01
Morris J. Karnovsky
The transendothelial passage of horseradish peroxidase, injected intravenously into mice, was studied at the ultrastructural level in capillaries of cardiac and skeletal muscle. Peroxidase appeared to permeate endothelial intercellular clefts … The transendothelial passage of horseradish peroxidase, injected intravenously into mice, was studied at the ultrastructural level in capillaries of cardiac and skeletal muscle. Peroxidase appeared to permeate endothelial intercellular clefts and cell junctions. Abnormal peroxidase-induced vascular leakage was excluded. Neutral lanthanum tracer gave similar results. The endothelial cell junctions were considered to be maculae occludentes, with gaps of about 40 A in width between the maculae, rather than zonulae occludentes. Some observations in favor of concurrent vesicular transport of peroxidase were also made. It is concluded that the endothelial cell junctions are most likely to be the morphological equivalent of the small pore system proposed by physiologists for the passage of small, lipid-insoluble molecules across the endothelium.
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Oxygen sensing and molecular adaptation to hypoxia

1996-07-01
H. Franklin Bunn , Robert Ο. Poyton
This review focuses on the molecular stratagems utilized by bacteria, yeast, and mammals in their adaptation to hypoxia. Among this broad range of organisms, changes in oxygen tension appear to … This review focuses on the molecular stratagems utilized by bacteria, yeast, and mammals in their adaptation to hypoxia. Among this broad range of organisms, changes in oxygen tension appear to be sensed by heme proteins, with subsequent transfer of electrons along a signal transduction pathway which may depend on reactive oxygen species. These heme-based sensors are generally two-domain proteins. Some are hemokinases, while others are flavohemoproteins [flavohemoglobins and NAD(P)H oxidases]. Hypoxia-dependent kinase activation of transcription factors in nitrogen-fixing bacteria bears a striking analogy to the phosphorylation of hypoxia inducible factor-1 (HIF-1) in mammalian cells. Moreover, redox chemistry appears to play a critical role both in the trans-activation of oxygen-responsive genes in unicellular organisms as well as in the activation of HIF-1. In yeast and bacteria, regulatory operons coordinate expression of genes responsible for adaptive responses to hypoxia and hyperoxia. Similarly, in mammals, combinatorial interactions of HIF-1 with other identified transcription factors are required for the hypoxic induction of physiologically important genes.

Protein secondary structures in water from second-derivative amide I infrared spectra

1990-04-03
A. Dong , Huang Ping , Winslow S. Caughey
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtein secondary structures in water from second-derivative amide I infrared spectraAichun Dong, Ping Huang, and Winslow S. CaugheyCite this: Biochemistry 1990, 29, 13, 3303–3308Publication Date (Print):April 3, … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtein secondary structures in water from second-derivative amide I infrared spectraAichun Dong, Ping Huang, and Winslow S. CaugheyCite this: Biochemistry 1990, 29, 13, 3303–3308Publication Date (Print):April 3, 1990Publication History Published online1 May 2002Published inissue 3 April 1990https://pubs.acs.org/doi/10.1021/bi00465a022https://doi.org/10.1021/bi00465a022research-articleACS PublicationsRequest reuse permissionsArticle Views6234Altmetric-Citations1110LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

<b>Contribution of Hydrophobic Interactions to the Stability of the Globular Conformation of Proteins</b>

1962-11-01
Charles Tanford
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTContribution of Hydrophobic Interactions to the Stability of the Globular Conformation of ProteinsCharles. TanfordCite this: J. Am. Chem. Soc. 1962, 84, 22, 4240–4247Publication Date (Print):November 1, 1962Publication … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTContribution of Hydrophobic Interactions to the Stability of the Globular Conformation of ProteinsCharles. TanfordCite this: J. Am. Chem. Soc. 1962, 84, 22, 4240–4247Publication Date (Print):November 1, 1962Publication History Published online1 May 2002Published inissue 1 November 1962https://pubs.acs.org/doi/10.1021/ja00881a009https://doi.org/10.1021/ja00881a009research-articleACS PublicationsRequest reuse permissionsArticle Views2539Altmetric-Citations843LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Blood gas calculator.

1966-05-01
John W. Severinghaus

The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves

1910-01-01
Archibald Vivian Hill , Anastacia L. Hill , A. Paganini-Hill

Avidin

1975-01-01
N. Michael Green

[45] Cytochrome oxidase from beef heart mitochondria

1967-01-01
David C. Wharton , Alexander Tzagoloff

Resuscitation from Hemorrhagic Shock With a Novel Protein Cocktail Restores Microvascular Perfusion and Protects Vital Organs

2025-06-23
Carlos Muñoz , Daniela Lucas , Ivan S. Pires +7 more | Shock
Low titer O positive Whole Blood (LTOWB) has been introduced in prehospital care to resuscitate patients; however, the logistical obstacles, cost of carrying LTOWB, and the availability of it in … Low titer O positive Whole Blood (LTOWB) has been introduced in prehospital care to resuscitate patients; however, the logistical obstacles, cost of carrying LTOWB, and the availability of it in trauma situations are a point of concern. Therefore, fluids, like Lactated Ringer's (LR) and hydroxyethyl starch (HES) have been considered alternatives to LTOWB transfusion. Unfortunately, they dilute plasma proteins in the circulation and have unfavorable side effects. This study presents an alternative, a Protein Cocktail (PC). The PC combines human serum albumin, transferrin, haptoglobin, and hemopexin. This study compares the ability to resuscitate from hemorrhagic shock (HS) with Whole Blood (WB), LR, 6% HES, and PC. Unanesthetized Golden Syrian hamsters instrumented with the dorsal window chambers were subjected to hemorrhage (50% blood volume), followed by 30 min hypovolemic shock, and resuscitated with 50% shed volume. The outcome was evaluated through systemic parameters, blood gases, microcirculatory hemodynamics, oxygen tension and saturation, metabolomics, and markers of organ injury/function. Additionally, to investigate the impact of the experimental solutions on the coagulation cascade, Sprague Dawley rats were subjected to an isovolemic exchange-infusion of 20% of the animal's blood volume. The PC showed favorable outcomes, restoring microvasculature hemodynamics comparable to resuscitation with Whole Blood and superior to Lactated Ringer's and HES. PC reduced acute inflammation, positively impacted organ function markers, and restore metabolomic homeostasis without coagulopathies observed with HES. In conclusion, the Protein Cocktail (PC) shows some promise as a resuscitation from hemorrhagic shock when Whole Blood is not available, and superior to classic crystalloids and colloids (LR and HES). Further studies with the PC are needed to ensure its efficacy and safety in other experimental models.

Corrigendum to “Artificial Oxygen Carriers—Past, Present, and Future—a Review of the Most Innovative and Clinically Relevant Concepts”

2025-06-23
Katja B. Ferenz , Andrea U. Steinbicker | Journal of Pharmacology and Experimental Therapeutics

A small rapid donor blood cooler

2025-06-19
А. Г. Гудков , V. Yu. Leushin , S. V. Agasieva +5 more | Biomedical Engineering

Integrative computational approaches identify haptoglobin inhibitors to modulate erythrocyte sedimentation rate in trauma-linked inflammatory and haematological malignancies

2025-06-18
Abdulaziz H. Al Khzem , Shaban Ahmad | Frontiers in Chemistry
Elevated levels of haptoglobin are commonly observed in conditions characterised by an increased erythrocyte sedimentation rate which are acute-phase reactants. These conditions include infection, trauma, inflammation, hepatitis, amyloidosis, collagen diseases, … Elevated levels of haptoglobin are commonly observed in conditions characterised by an increased erythrocyte sedimentation rate which are acute-phase reactants. These conditions include infection, trauma, inflammation, hepatitis, amyloidosis, collagen diseases, lymphoma, leukaemia, as well as obstructive and biliary diseases. However, no significant drugs are currently available to manage these conditions, making therapeutic intervention crucial effectively. In this study, we performed an extensive screening of the DrugBank database against the human haptoglobin protein (PDB ID: 4X0L) using High-Throughput Virtual Screening (HTVS), Standard Precision and Extra Precision (XP) docking methods, followed by pose processing with Molecular Mechanics Generalised Born Surface Area (MM/GBSA) calculations. This led to the identification of five potential inhibitors: L-histidinol phosphate (DB03997), L-gluconic acid (DB04304), 4-bromo-3-(carboxymethoxy)-5-(4-hydroxyphenyl)thiophene-2-carboxylic acid (DB07197), 3-O-methylfructose (DB02438), and glutamine hydroxamate (DB02446), with docking scores ranging from −7.96 to −5.58 kcal/mol and MM/GBSA scores between −26.23 and −1.00 kcal/mol. The study also included Density Functional Theory computations and pharmacokinetic profiling to assess these compounds’ suitability further, revealing promising results. Additionally, we conducted molecular interaction fingerprint analysis, revealing key residues involved in interactions, including 10LYS (Basic), 8LEU (non-polar), 7ASP (Acidic), and 7THR (Polar), indicating a mixed interaction profile. A 5 ns WaterMap analysis was used to identify optimal hydration sites and interaction patterns. Moreover, a 100 ns molecular dynamics (MD) simulation using the TIP3P water model in the NPT ensemble confirmed the stability of the protein-ligand complexes, with acceptable deviations, fluctuations, and intermolecular interactions. MM/GBSA calculations on the simulation trajectories supported these findings by providing binding free energy and complex energy estimations for all protein-ligand complexes. Although these findings provide compelling computational evidence for haptoglobin inhibition, experimental studies must confirm its effectiveness before human use.

Analysis of β‐C‐terminal salt bridges in T‐state hemoglobin by trapping tertiary conformations in silica gels

2025-06-16
Naoya Shibayama | Protein Science
Abstract Encapsulation of a protein in wet silica gels greatly slows its large‐scale motions, allowing the characterization of defined protein conformations during functional and spectroscopic measurements. This technique has revealed … Abstract Encapsulation of a protein in wet silica gels greatly slows its large‐scale motions, allowing the characterization of defined protein conformations during functional and spectroscopic measurements. This technique has revealed the coexistence of two or more functionally distinct tertiary conformations in T‐state human hemoglobin, but their structural basis remains unclear. Here, we extend this approach to analyze the β‐C‐terminal salt bridges in the T‐state hemoglobin populations. To this end, we first compare three representative sol–gel trapping protocols by transient absorption characterization of both directions of the hemoglobin allosteric transition (R‐to‐T and T‐to‐R) and by O 2 equilibrium measurements. Results reveal protocol‐dependent variations in slow‐down factor for tertiary and quaternary conformational changes and demonstrate that our method most effectively traps tertiary hemoglobin conformations. Using this optimized protocol, we show that the kinetics of Cys93β sulfhydryl reactivity of T‐state Ni(II)‐substituted hemoglobin in silica gels is markedly biphasic under low‐salt conditions but monophasic in the presence of inositol hexakisphosphate. These findings provide direct evidence for the coexistence of high‐ and low‐affinity tertiary conformations with broken and unbroken β‐C‐terminal salt bridges, respectively, in the anion‐free T quaternary structure of hemoglobin and elucidate why the O 2 affinity of T‐state deoxyhemoglobin varies dramatically with solution conditions.

Multiple catalytic functions of an engineered double mutant of myoglobin with a potential metal-binding site

2025-06-15
Ai-Qun Pan , Xichun Liu , Lu Yu +3 more | Journal of Inorganic Biochemistry

Formation of extracellular vesicles depends on mechanical feedback of the cortex and the glycocalyx

2025-06-15
Ke Xiao , Padmini Rangamani | bioRxiv (Cold Spring Harbor Laboratory)
Cell-secreted extracellular vesicles (EVs) play a pivotal role in local and distant cell-to-cell communication by delivering specific cargoes to other cells or to the extracellular space. In many cells, the … Cell-secreted extracellular vesicles (EVs) play a pivotal role in local and distant cell-to-cell communication by delivering specific cargoes to other cells or to the extracellular space. In many cells, the glycocalyx, a thick sugar-rich layer at the cell surface, and the membrane-cortex attachment are crucially linked to the formation of EVs, yet it is unclear what determines the successful formation of EVs when multiple physical factors are involved. In this work, we developed a model for glycocalyx-membrane-cortex composite to investigate the effects of glycocalyx and membrane-cortex adhesion on the formation of EVs by combining polymer physics-based theory and Helfrich membrane theory. By performing linear stability analysis, we show that modulating the mechanical feedback among the glycocalyx, membrane-cortex attachment, and membrane curvature can give rise to two types of instabilities: a conserved Turing-type instability and a Cahn-Hilliard-type instability. Furthermore, using an equilibrium model, we identified two critical conditions for EV formation: an initial detachment of the membrane from the underlying cortex and then a sufficient driving force to induce membrane deformation for successful EV formation. We further demonstrated that there exists an optimal glycocalyx coating area at which the formation of EVs is most favorable. Finally, we use our model to predict that a heterogeneous size distribution of EVs can be generated through the regulation of glycocalyx properties, shedding insight into how EVs of different radii may be generated.

Allosteric Regulation of Heme-containing Respiratory Enzymes for Therapeutic Implications: Cytochrome <i>c</i> Oxidases and Nitric Oxide Reductases

2025-06-13
Yuya Nishida , Yasunori Shintani | Royal Society of Chemistry eBooks
The respiratory chain comprises electron transport and the subsequent ATP synthesis. This conserved mechanism is fundamental to life, and its dysfunction can lead to various human diseases. Complex IV is … The respiratory chain comprises electron transport and the subsequent ATP synthesis. This conserved mechanism is fundamental to life, and its dysfunction can lead to various human diseases. Complex IV is the rate-limiting step of the respiratory chain; thus, modulating its activity on demand will have therapeutic implications. Our group has identified Higd1a as a positive allosteric regulator of mitochondrial cytochrome c oxidase (mtCcO), enhancing mitochondrial function under stress. In searching for allosteric modulators for mtCcO, we revealed a novel allosteric inhibitory site that is conserved among the heme–copper oxidoredactase (HCO) superfamily. Understanding allosteric mechanisms and structural differences between eukaryotic and prokaryotic HCOs can lead to rationally developing a novel antibiotic targeting drug-resistant bacteria. This chapter explores allosteric regulatory mechanisms of Complex IV and their therapeutic potential.

Statistical Insight into Heme Structures and Their Diverse Utility in Proteins

2025-06-13
Yoshiko Kanematsu , Hiroko Kondo , Yu Takano | Royal Society of Chemistry eBooks
In this chapter, developments, applications, and recent updates of PyDISH and other online services of databases and analytic tools for heme protein research are introduced, which will be indispensable for … In this chapter, developments, applications, and recent updates of PyDISH and other online services of databases and analytic tools for heme protein research are introduced, which will be indispensable for understanding how the proteins make modifications to their heme cofactor to elicit their functions and how we should implement their artificial function by mimicking them.

Proteins Associated with Haem Catabolism for Iron Utilisation and Other Functions in Mammals and Photosynthetic Organisms

2025-06-13
Masakazu Sugishima , Kei Wada , Junichi Taira | Royal Society of Chemistry eBooks
Free haem is oxidatively catabolised to ferrous ions, carbon monoxide, and biliverdin to prevent reactive oxygen species generation. In mammals, ferrous ions produced during haem catabolism are essential for maintaining … Free haem is oxidatively catabolised to ferrous ions, carbon monoxide, and biliverdin to prevent reactive oxygen species generation. In mammals, ferrous ions produced during haem catabolism are essential for maintaining iron homeostasis. In addition, other products are believed to be essential for antioxidant activity and signal transduction. Other organisms utilise this reaction to obtain iron as an essential nutrient and pigments for light-dependent reactions such as photosynthesis. In this chapter, biochemical and structural studies of enzymes involved in haem degradation and biliverdin reduction in mammals, pathogens, and photosynthetic organisms are summarised.

1314-P: Association of Haptoglobin Levels and Phenotype with Cardiovascular Disease in Adults with Type 2 Diabetes—A FIELD Trial Substudy

2025-06-13
Kwok Leung Ong , ANDRZEJ S. JANUSZEWSKI , HABIB FRANCIS +7 more | Diabetes
Introduction and Objective: Haptoglobin (HP) is a circulating glycoprotein with antioxidant and anti-inflammatory properties. It scavenges toxic free hemoglobin. Cardiovascular disease (CVD) risk in Type 2 diabetes (T2D) patients may … Introduction and Objective: Haptoglobin (HP) is a circulating glycoprotein with antioxidant and anti-inflammatory properties. It scavenges toxic free hemoglobin. Cardiovascular disease (CVD) risk in Type 2 diabetes (T2D) patients may differ by HP phenotype. It is unknown if CVD risk and fenofibrate benefits differ by HP levels. Methods: HP phenotype and levels were measured in baseline plasma from 8047 T2D adults in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial by ELISA and immunoturbidimetric assay, respectively. Results: Frequencies of HP 1-1, 2-1 and 2-2 phenotypes were 15.6%, 47.6% and 36.9% respectively. Higher HP level tertiles, but not HP phenotype, were associated with a higher risk of total CVD events, especially coronary heart disease events (P=0.019) and CVD mortality (P=0.003) in placebo group, after adjustment for CVD risk factors (overall P for trend =0.032, Fig. 1A). The HP level association was independently significant only in the HP 1-1 phenotype (P for level/phenotype interaction =0.039, Fig. 1B). Participants with both HP 1-1 phenotype and the lowest HP tertile levels tended to have the lowest CVD risk (Fig. 1C). Fenofibrate benefits on total CVD events did not differ by HP phenotype or levels. Conclusion: HP levels and phenotype help to identify T2D patients at high CVD risk for treatment, especially those with HP 1-1 phenotype. Disclosure K. Ong: None. A.S. Januszewski: None. H. Francis: None. R.L. O'Connell: None. A. Mangani: None. L. Li: None. P.G. Colman: None. D. Sullivan: Other Relationship; Amgen Inc. Research Support; Arrowhead Pharmaceuticals, Inc. Other Relationship; Novartis Pharmaceuticals Corporation, Merck Sharp &amp; Dohme Corp. Research Support; Ionis Pharmaceuticals. J.D. Best: None. R.S. Scott: None. A. Jenkins: Advisory Panel; Abbott. Speaker's Bureau; GlaxoSmithKline plc. Research Support; Abbott, Metronics, Ypsomed AG, Insulet Corporation, Jaeb Center for Health Research, Endogenex, Hemsley Charitable Trust. Speaker's Bureau; CSL Seqirus. Research Support; AbbVie Inc, National Institutes of Health, Juvenile Diabetes Research Foundation (JDRF). A.C. Keech: Research Support; Abbott, Amgen Inc, ASPEN Australia, Mylan. Speaker's Bureau; Novartis AG, Pfizer Inc. Research Support; Kowa Company, Ltd. Speaker's Bureau; Sanofi. Research Support; AbbVie Inc, Viatris Inc. Funding Laboratoires Fournier, Dijon, France and the National Health and Medical Research Council of Australia (457103, 1024105, 1037786, 1105467, 1121272, 1137071 and 2018537)

Atypical Pappenheimer bodies mimicking basophilic stippling in myelodysplastic syndrome with pulmonary embolism

2025-06-12
Si Chen , Qin Zheng | British Journal of Haematology

Damage to the Peptidoglycan in the Cell Wall Caused by Reactive Oxygen Species: A Molecular Dynamics Simulation

2025-06-11
Weizhong Tang , Qiaoyue Chen , Danfeng Liu +2 more | The Journal of Physical Chemistry B
Using molecular dynamics simulations with the ReaxFF force field, we investigate the oxidization mechanism of reactive oxygen species (ROS) on three different peptidoglycans (PGs) in an aqueous environment, which are … Using molecular dynamics simulations with the ReaxFF force field, we investigate the oxidization mechanism of reactive oxygen species (ROS) on three different peptidoglycans (PGs) in an aqueous environment, which are A3α type, A1γ type, and B1α type, respectively. Our findings revealed ROS can dehydrogenate and break C-C and C-O bonds. We identified distinct mechanisms for C-O bond dissociation, which occurred in four contexts: on MurNAc, on GlcNAc, and between MurNAc and GlcNAc, as well as between the stem peptide and MurNAc. Additionally, we observed a C-C dissociation mechanism occurring on GlcNAc. However, no dissociation mechanism for C-N bonds was detected even when the temperature was increased. Moreover, we found that ROS had a significantly higher capacity to extract H atoms from O atoms than C atoms. Under the same concentration of ROS, we noted that the dehydrogenation ratio of A3α type PG was the most facile, even though the dissociation of C-C and C-O bonds was relatively weak. In contrast, the B1α type PG exhibited the lowest dehydrogenation ratio while showing the highest dissociation rates for C-C and C-O bonds, with A1γ type PG in between them. This study offers new insights into understanding the bactericidal effects of plasma at the atomic level.

Nano-haemoglobin-based oxygen carrier increases the radiosensitivity of non-small-cell lung cancer

2025-06-01
Changmin Liu , Yong Li , Shanhui Feng +5 more | Artificial Cells Nanomedicine and Biotechnology
Haemoglobin-based oxygen carriers (HBOCs) could improve the hypoxic state of non-small-cell lung cancer (NSCLC) and increase radiotherapy sensitivity. We assessed the in vitro effects of nano-HBOC + irradiation therapy (IR) … Haemoglobin-based oxygen carriers (HBOCs) could improve the hypoxic state of non-small-cell lung cancer (NSCLC) and increase radiotherapy sensitivity. We assessed the in vitro effects of nano-HBOC + irradiation therapy (IR) on NSCLC cells and the in vivo effect on a mouse model. H385 human NSCLC cell line was used to evaluate the nano-HBOC effect + IR on the cellular partial pressure of oxygen (pO2), cell activity and changes in reactive oxygen species (ROS) 1-2 h post-exposure. An NSCLC tumour-bearing mouse model was established to evaluate nano-HBOC+IR efficacy 28 d post-exposure. In vitro, pO2 tended to increase in nano-HBOC groups versus control, cell activity decreased (p < 0.01) and ROS level increased (p < 0.05). Post-irradiation, pO2 increased in nano-HBOC+IR groups versus control (p < 0.01), viability decreased (p < 0.01) and ROS increased (p < 0.01). No significant difference between nano-HBOC groups was observed. In vivo, nano-HBOC was most abundant at the tumour site and pO2 increased 6 h post-injection (p > 0.05). Tumour size was smaller in the IR and nano-HBOC+IR groups versus control. ROS levels and cell death were significantly increased. Nano-HBOC can improve pO2, enhance radiotherapy's inhibitory ability on NSCLC cell lines and tumour-bearing mouse models, and promote ROS release.

Direct determination of kinetic parameters for the hydrolysis of a poor substrate by human plasma

2025-06-01
Jure Stojan | Chemico-Biological Interactions

The Rationalization of Carbon Monoxide and Hemoglobin Association

2025-05-31
Chihjen Lee , Nikki Chen | bioRxiv (Cold Spring Harbor Laboratory)
Carbon monoxide is a colorless, odorless, and poisonous gas, responsible for approximately 100,000 emergency room visits and over 420 deaths in the U.S. each year. Both carbon monoxide and oxygen … Carbon monoxide is a colorless, odorless, and poisonous gas, responsible for approximately 100,000 emergency room visits and over 420 deaths in the U.S. each year. Both carbon monoxide and oxygen bind to the ferrous ions in hemoglobin, but carbon monoxide has a significantly higher affinity. Extensive research has been conducted on the interaction between carbon monoxide and hemoglobin. However, a straightforward and practically applicable equation describing the relationship between carbon monoxide saturation and pressure is not found in the existing literature. In this paper, we establish an equation and confirm that the plot of CO saturation against CO pressure follows a hyperbolic shape, characterized by a continuous decrease in slope. In contrast, the oxygen-hemoglobin association curve is sigmoidal. These distinct curve shapes have different physiological implications. Our equation enables the determination of one variable, either saturation or pressure, if the other is known. Further analysis reveals the distribution of all five species of carboxyhemoglobin, showing that the triply bound form is abundant, a notable contrast to the distribution of oxyhemoglobin species. Additionally, our equation confirms that carbon monoxide's affinity for hemoglobin is approximately 230 times higher than that of oxygen. Lastly, we propose a new general equation that may generate all carbon monoxide-hemoglobin association curves under various oxygen pressures.

Heme-proteins tyrosine nitration mediated by the photolysis of 5-methyl-1,4-dinitroimidazol (DNI)

2025-05-30
Natalia Ríos , Adrián Aicardo , Mauricio Mastrogiovanni +4 more | Free Radical Biology and Medicine

GROMOS-RONS: A Force Field for Simulations of Reactive Oxygen and Nitrogen Species

2025-05-29
Rodrigo M. Cordeiro | The Journal of Physical Chemistry B
Reactive oxygen and nitrogen species (RONS) play pivotal roles in biological and atmospheric systems, yet their transient nature challenges experimental study. Molecular dynamics (MD) simulations offer a powerful alternative, as … Reactive oxygen and nitrogen species (RONS) play pivotal roles in biological and atmospheric systems, yet their transient nature challenges experimental study. Molecular dynamics (MD) simulations offer a powerful alternative, as long as reliable molecular mechanical models are available that accurately reproduce key physical properties of the simulated species. Correct partitioning behavior is crucial for biomolecular and atmospheric chemistry simulations, where RONS interactions at interfaces─such as phospholipid membranes and water-air boundaries─underpin essential processes. This study presents GROMOS-RONS, a force field for MD simulations of RONS and related compounds within the framework of the GROMOS 53A6 and 54A7 force field families. By integrating electronic structure calculations, thermodynamic integration, and equilibrium MD simulations, parameters were optimized to reproduce solvation free energies of various RONS in both water and hydrophobic media. In the case of ionic species, emphasis was placed on the correct hydration structure and ion-pairing tendencies. This force field provides a robust, validated tool for studying RONS dynamics and interactions across diverse scientific domains.

Heterologous expression of flavohemoglobin in Rhodotorula toruloides led to improved lipid production

2025-05-26
Steve M. F. Lai , Liting Lyu , Aabid Manzoor Shah +4 more

Novel neuroglobin boosters as a therapeutic strategy for traumatic brain injury Ngb boosters for TBI therapy

2025-05-22
Oscar Hidalgo‐Lanussa , Tabata Barbosa-Rojas , Paulina Valenzuela-Hormazábal +3 more
Neuroglobin (Ngb) induction offers a promising strategy for mitigating traumatic brain injury (TBI) damage due to its intrinsic antioxidant properties and capacity to alleviate oxidative stress. In this study, we … Neuroglobin (Ngb) induction offers a promising strategy for mitigating traumatic brain injury (TBI) damage due to its intrinsic antioxidant properties and capacity to alleviate oxidative stress. In this study, we employed high-throughput bioinformatics analysis to identify specific compounds that modulate Ngb-related mechanisms, followed by in vitro evaluation of their effects in astrocyte cultures. Among the compounds screened, A1 and A4 emerged as the most potent Ngb inducers. Immunocytochemistry revealed that A1 significantly increased Ngb intensity by 22 %, while A4 enhanced it by 25 %. Additionally, western blot analysis demonstrated that A1 treatment resulted in a threefold increase in Ngb expression compared to controls. Both compounds also improved cell viability, with A1 increasing viability by 8 % and A4 by 25 % relative to untreated controls. Furthermore, our results indicate that these compounds regulate mitochondrial function, enhancing cellular respiration, and potentially reducing energy demand under basal conditions. The complex interactions between Ngb and mitochondrial components, along with their role in various cellular signalling pathways, highlights the need for further research to fully elucidate Ngb's mechanisms of action. In conclusion, compounds A1 and A4 are promising candidates for developing innovative neuroprotective therapies, warranting ongoing exploration of their therapeutic implications.

Artificial Oxygen Carriers (Blood Substitutes): A Pathway Forward?

2025-05-22
Ying Hui Low , Jonathan S. Jahr , Steven M. Frank

Spectroscopic Interrogation of Thiolate Hydrogen Bonding in the CO Sensor Protein CooA: Implications for Thiolate Ligation Stability and Cytochrome P450 Function

2025-05-21
Brian R. Weaver , Richard J. Jodts , Brian M. Hoffman +2 more
Cysteine (Cys) thiolate coordination is a unique ligation motif found in heme enzymes and small molecule sensors. Divergence between these two functional classes of heme thiolate proteins is a result … Cysteine (Cys) thiolate coordination is a unique ligation motif found in heme enzymes and small molecule sensors. Divergence between these two functional classes of heme thiolate proteins is a result of distinct hydrogen bonding interactions with the axial Cys(thiolate) ligand. We report a spectroscopic analysis of thiolate H‐bonding in CooA, a carbon monoxide‐sensing heme protein from Rhodospirillum rubrum that is known to switch between Cys75(thiolate) and histidine coordination upon reduction. We generated CooA variants with alterations at two residues, Asn42 and His77, which are postulated to influence H‐bonding to Cys75 on the basis of an Fe(II) CooA structure. Using a combination of electronic absorption, electron paramagnetic resonance (EPR) and electron nuclear double resonance (ENDOR) spectroscopies, we identified several CooA variants that exhibit changes in thiolate donor strength and propose an H‐bonding model in which Asn42 orients His77 for optimal H‐bonding with Cys75 in Fe(III) CooA. Further, we spectroscopically characterize pyrrolidine‐bound CYP119 to mimic the first coordination sphere of Fe(III) CooA. We show that CooA contains a stronger thiolate‐Fe bond than the pyrrolidine‐bound CYP119, suggesting that Cys(thiolate) H‐bonding interactions in CooA are significantly weaker. These results suggest thiolate H‐bonding is a significant differentiator between the two classes of heme thiolate proteins.

Perfluorocarbon nanoemulsions decrease hypoxia in cell culture

2025-05-21
Aisling Mann , Andrea Leiva , Lydia M. Robbins +1 more

Molecularly Defined Glycocalyx Models Reveal AB<sub>5</sub> Toxins Recognize Their Target Glycans Superselectively

2025-05-20
Laia Saltor Núñez , Vajinder Kumar , James F. Ross +5 more

Lysine Lactylation of Hemoglobin Promotes Oxygen Release in Red Blood Cells

2025-05-19
Ming Sheng , Huiqin Jin , Shiyu Tao +6 more

Veterinary Perspectives on Hemoglobin-Based Oxygen Carriers in Experimental Hemorrhagic Shock: Insights from Rabbit Models

2025-05-16
Ștefania-Mădălina Dandea , Alina-Diana Hașaș , Vlad-Alexandru Toma +7 more
Hemoglobin-based oxygen carriers (HBOCs) represent a promising alternative to traditional blood transfusions, offering the advantages of extended shelf life and avoiding blood compatibility limitations and infection risks. Positive effects of … Hemoglobin-based oxygen carriers (HBOCs) represent a promising alternative to traditional blood transfusions, offering the advantages of extended shelf life and avoiding blood compatibility limitations and infection risks. Positive effects of hemoglobin-based oxygen carriers (HBOCs) on hemorrhagic shock have been researched across various animal species, including swine, rats, rabbits, guinea pigs, and dogs. As previously described, HBOCs based on ovine hemoglobin display better efficiency in the context of hemorrhagic shock compared to those based on the more commonly used bovine hemoglobin. This was evidenced through higher survival rates and more favorable histopathological and immunological outcomes. The vascular effects of ovine hemoglobin polymerized with glutaraldehyde exposure included the absence of hypertension, minimal endothelial damage with slight alterations in inducible nitric oxide synthase (iNOS), and reduced vascular inflammation mediated by interleukin-10 (IL-10). Ovine hemoglobin has emerged as a particularly promising raw material for the development of HBOCs, surpassing bovine and human hemoglobin due to its advantages in availability and efficacy. Furthermore, reducing oxidative stress by polymerizing hemoglobin with glutaraldehyde is most effective with ovine hemoglobin compared to bovine hemoglobin. This study evaluates the effectiveness of ovine hemoglobin polymerized with glutaraldehyde in managing hemorrhagic shock in rabbits, with a focus on its ability to maintain blood pressure, support oxygen transport, and assess potential systemic and oxidative responses. Fifteen adult New Zealand white rabbits, divided into three equal groups, were included in this study: a negative control group transfused with colloid solutions, a positive control group treated with autotransfusion, and a group receiving HBOCs. All groups underwent a hemorrhagic shock protocol, with 40% of their total blood volume withdrawn under deep anesthesia, followed by transfusions 30 min later. Vital parameters, including invasive arterial blood pressure, heart rate, and end-tidal CO2, were measured throughout the experimental procedures. Arterial blood gas samples were collected before the procedures, after hemorrhagic shock induction, and at the conclusion of the transfusion. In summary, HBOCs offer a promising solution for oxygen delivery, but their effects on blood chemistry, particularly CO2 and lactate levels, must be considered. Although no direct oxygenation issues were observed in experimental models, elevated CO2 levels and the interference of HBOCs with lactate measurements emphasize the importance of vigilant clinical monitoring. Polymerized hemoglobin provides a non-nephrotoxic alternative, but challenges persist in preventing nitric oxide scavenging and ensuring effective oxygen delivery.

HmuY proteins of the Porphyromonas genus show diversity in heme-binding properties

2025-05-13
Michał Śmiga , Teresa Olczak
Bacteria of the Porphyromonas genus, belonging to the Bacteroidota phylum, colonize various host niches in health and disease. As heme auxotrophs, they rely on heme uptake for iron and protoporphyrin … Bacteria of the Porphyromonas genus, belonging to the Bacteroidota phylum, colonize various host niches in health and disease. As heme auxotrophs, they rely on heme uptake for iron and protoporphyrin IX. A key heme acquisition system in Porphyromonas gingivalis is the Hmu system, where the hemophore-like HmuYPg protein plays a major role. HmuYPg coordinates heme-iron using two histidines, whereas other known HmuY proteins produced by other Bacteroidota members prefer a pair of histidine-methionine or two methionines. Some of them bind heme via the protoporphyrin ring without heme-iron coordination, similar to the P. gingivalis HusA protein. This study used bioinformatics, spectroscopic, and electrophoretic methods to compare the genomic organization of the Hmu system and the structural and functional properties of HmuY proteins within the Porphyromonas genus. We revealed variations in the heme-binding properties of proteins belonging to the HmuY family and susceptibility to modifications in their heme-binding pockets. These findings suggest that HmuY proteins may have undergone evolutionary adaptations to enhance bacterial survival in the human microbiome, contributing to dysbiosis and disease development. These evolutionary changes may explain the superior heme-binding ability of P. gingivalis HmuYPg compared to HmuY homologs produced by other Porphyromonas species.

Ion kinetic effects in the overtaking and coalescence of plasma shocks

2025-05-08
E. H. Zhang , Zihan Lin , Wenshuai Zhang +7 more
Abstract The overtaking and coalescence of plasma shocks are important scientific topics in inertial confinement fusion (ICF) design.&amp;#xD; We present the comparative study of the impact of ion kinetic effects … Abstract The overtaking and coalescence of plasma shocks are important scientific topics in inertial confinement fusion (ICF) design.&amp;#xD; We present the comparative study of the impact of ion kinetic effects on the overtaking and coalescence of two shocks in deuterium (D) plasmas of various densities with both hybrid fluid-PIC (particle-in-cell) simulations and hydrodynamic simulations.&amp;#xD; It is found that the energetic ions escaping from 2nd shock can prevent the compression of the fuel layer, by accelerating and heating upstream plasmas.&amp;#xD; In the strong-collision case (rho_D &gt; rho_th = 30mg/cc), the coalescent density is reduced by about 8% due to the decreased shock Mach number resulting from energetic ion deposition in the upstream region.&amp;#xD; In the weak-collision case (rho_D &lt; rho_th), the conversion efficiency of ion kinetic energy to internal energy is inhibited due to the increased ion mean free path, and the coalescent pressure is reduced by about 23%.&amp;#xD; In addition, the fast-velocity ions with a velocity v_i \sim 4\times10^{-3} c can drift further with a approximately constant velocity, which can result in an increased entropy in the central vapor region.&amp;#xD; This mechanism offers a potential explanation for persistently overestimated fuel compression in design simulations of layered implosions.&amp;#xD; These results also provide a new dataset valuable for benchmarking radiation hydrodynamic models and improving understanding of shock physics.

Methodological strategies to study and elucidate RBC properties and their potential clinical impact on transfused patients

2025-05-01
Emmanuel Längst , Michel Prudent