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Modeling Red Blood Cell Metabolism in the Omics Era

METABOLITES (2023)

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Article Hematology

Sphingosine 1-phosphate has a negative effect on RBC storage quality

Ariel Hay et al.

Summary: Blood storage leads to the decrease of ATP and DPG in red blood cells, which play crucial roles in erythrocyte physiology, oxygen kinetics, and posttransfusion survival. Supplementing S1P to stored RBC units can improve energy metabolism and posttransfusion recovery.

BLOOD ADVANCES (2023)

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Article Hematology

In vivo evaluation of the effect of sickle cell hemoglobin S, C and therapeutic transfusion on erythrocyte metabolism and cardiorenal dysfunction

Angelo D'Alessandro et al.

Summary: This study evaluates the red blood cell metabolism of 587 sickle cell disease patients and finds significant metabolic alterations in RBC acylcarnitines, pyruvate, sphingosine 1-phosphate, creatinine, kynurenine, and urate in Hb SS genotype compared to AA and SC RBCs. Surprisingly, the metabolism of SC RBCs is dramatically different from SS RBCs, with all glycolytic intermediates significantly elevated. These findings provide insights into the metabolic signatures and potential underlying mechanisms in sickle cell disease.

AMERICAN JOURNAL OF HEMATOLOGY (2023)

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Article Biochemistry & Molecular Biology

GotEnzymes: an extensive database of enzyme parameter predictions

Feiran Li et al.

Summary: Enzyme parameters are crucial for understanding, modeling, and engineering cells. Experimental measurements only cover a small portion of enzyme-compound pairs, and even less in non-model organisms. Artificial intelligence techniques have accelerated the exploration of enzyme properties by predicting them in a high-throughput manner. GotEnzymes is a comprehensive database that provides predicted enzyme parameters using AI approaches, allowing for interactive web exploration and programmatic access.

NUCLEIC ACIDS RESEARCH (2023)

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Article Multidisciplinary Sciences

Data integration across conditions improves turnover number estimates and metabolic predictions

Philipp Wendering et al.

Summary: Turnover numbers of enzymes are a key property that can improve the prediction accuracy of cellular phenotypes in metabolic modeling. However, in vitro and in vivo turnover numbers alone do not lead to accurate predictions of condition-specific growth rates of E. coli and S. cerevisiae, especially when considering protein abundances. By correcting turnover numbers using proteomics and physiological data, we demonstrate improved predictions of condition-specific growth rates. Our approach provides a means to correct turnover numbers and catalog kcatomes of other organisms.

NATURE COMMUNICATIONS (2023)

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Article Hematology

Metabolic signatures of cardiorenal dysfunction in plasma from sickle cell patients as a function of therapeutic transfusion and hydroxyurea treatment

Angelo D’Alessandro et al.

HAEMATOLOGICA (2023)

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Article Hematology

A novel missense variant in ATP11C is associated with reduced red blood cell phosphatidylserine flippase activity and mild hereditary hemolytic anemia

Myrthe J. van Dijk et al.

Summary: Mutations in the ATP11C gene result in decreased activity of the PS flippase, leading to hemolytic anemia. The deficiency of ATP11C causes an increase in PS exposure on the red blood cell membrane, abnormal membrane structure, and altered flow behavior of red blood cells.

AMERICAN JOURNAL OF HEMATOLOGY (2023)

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Article Hematology

Biphosphoglycerate Mutase: A Novel Therapeutic Target for Malaria?

Alessia Azzuolo et al.

TRANSFUSION MEDICINE REVIEWS (2023)

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Review Biochemistry & Molecular Biology

Red Blood Cell Metabolism In Vivo and In Vitro

Angelo D'Alessandro et al.

Summary: Red blood cells play a central role in oxygen transport in the human body. Recent advancements in omics technologies have revealed the complex proteome and metabolome of red blood cells, leading to a reevaluation of the mechanisms underlying RBC metabolism. These findings have also provided insights into changes that occur during refrigerated storage of RBCs in blood banks, which are crucial for life-saving transfusions worldwide.

METABOLITES (2023)

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Review Hematology

Red Blood Cell Omics and Machine Learning in Transfusion Medicine: Singularity Is Near

Angelo D'Alessandro

Summary: With the advancement of high-throughput omics technologies, transfusion medicine has been able to explore the biology of blood donors, stored blood products, and transfusion recipients. These approaches have revealed the impact of genetic and non-genetic factors on the quality of stored blood products and efficacy of transfusion events. In the near future, precision transfusion medicine arrays and metabolomics will enable the development and implementation of machine learning strategies for personalized transfusion medicine.

TRANSFUSION MEDICINE AND HEMOTHERAPY (2023)

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Article Biochemical Research Methods

Irradiation Causes Alterations of Polyamine, Purine, and Sulfur Metabolism in Red Blood Cells and Multiple Organs

Micaela Kalani Roy et al.

Summary: Investigating the metabolic effects of radiation on multiple organs and its interaction with iron overload, this study found that radiation can increase polyamines and purine salvage metabolites in organs with high oxygen consumption, and also impact the metabolism of the duodenum, colon, and stool, potentially affecting the microbiome.

JOURNAL OF PROTEOME RESEARCH (2022)

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Article Physiology

Deuterated Linoleic Acid Attenuates the RBC Storage Lesion in a Mouse Model of Poor RBC Storage

Christopher Y. Kim et al.

Summary: In this study, the effects of deuterated linoleic acid (DLA) on the storage quality of red blood cells (RBCs) were investigated. The results showed that DLA reduced lipid peroxidation, improved RBC deformability, filterability, and post-transfusion recovery. Particularly, the effects of DLA were more significant in mice with poor storage quality.

FRONTIERS IN PHYSIOLOGY (2022)

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Review Biochemistry & Molecular Biology

Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications

Brent R. Stockwell

Summary: This review describes the key regulators of ferroptosis and provides an overview of metabolism, ROS biology, and iron biology. Additionally, it highlights the important concepts and unanswered questions in the field of ferroptosis. The future holds promise for further breakthroughs in understanding the mechanisms of ferroptosis and utilizing it for therapeutic purposes.

CELL (2022)

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Article Physiology

Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosis

Alexis Caulier et al.

Summary: Hereditary xerocytosis is a red cell membrane disorder caused by PIEZO1 gene mutations. Proteomic analysis reveals significant changes in protein expression in patients' red blood cells, particularly in pathways related to protein assembly and ubiquitination.

FRONTIERS IN PHYSIOLOGY (2022)

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Article Biochemistry & Molecular Biology

Hemoglobin is an oxygen-dependent glutathione buffer adapting the intracellular reduced glutathione levels to oxygen availability

Simone Fenk et al.

Summary: This study identifies an adaptive mechanism in red blood cells where the levels of intraerythrocytic GSH increase upon deoxygenation, providing an advanced antioxidant defense. This effect is regulated by the oxygen-dependent modulation of Hb levels and involves the non-covalent binding of GSH to oxy-Hb. The findings suggest that red blood cells can respond immediately to oxidative challenges by adjusting GSH levels upon deoxygenation.

REDOX BIOLOGY (2022)

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Article Multidisciplinary Sciences

The bending rigidity of the red blood cell cytoplasmic membrane

Sebastian Himbert et al.

Summary: The membrane bending modulus, kappa, is an important mechanical property of cells, especially red blood cells. By studying the bending of red blood cell cytoplasmic membranes in the absence of spectrin and ATP, we found that the relatively small membrane bending modulus may confer advantages in biological processes.

PLOS ONE (2022)

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Article Hematology

Protein-L-isoaspartate O-methyltransferase is required for in vivo control of oxidative damage in red blood cells

Angelo D'Alessandro et al.

Summary: Red blood cells face the challenge of high levels of reactive oxygen species and lack the ability to synthesize new gene products. While progress has been made in understanding how RBC neutralize reactive oxygen species, little is known about how they repair damage caused by oxidative stress. RBC can only repair oxidized proteins directly and face challenges in repairing damage caused by reactive oxygen species.

HAEMATOLOGICA (2021)

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Article Medicine, Research & Experimental

Blood donor exposome and impact of common drugs on red blood cell metabolism

Travis Nemkov et al.

Summary: Computational models suggest that mature erythrocytes may be affected by common drugs. High-throughput drug screenings show that many drugs impact erythrocyte metabolism, with machine learning models accurately predicting these effects. Certain drugs like ranitidine can improve erythrocyte metabolism and storage quality, indicating potential for enhancing blood transfusion outcomes.

JCI INSIGHT (2021)

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MASSpy: Building, simulating, and visualizing dynamic biological models in Python using mass action kinetics

Zachary B. Haiman et al.

Summary: The article introduces the MASSpy package, an open-source computational framework for dynamic modeling of metabolism using mass action kinetics and detailed chemical mechanisms. By adding dynamic modeling tools to the COBRApy package, MASSpy provides a unified framework for constraint-based and kinetic modeling of metabolic networks. MASSpy supports high-performance dynamic simulation using libRoadRunner: the Systems Biology Markup Language (SBML) simulation engine.

PLOS COMPUTATIONAL BIOLOGY (2021)

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Article Physiology

Red Blood Cell Metabolism in Pyruvate Kinase Deficient Patients

Micaela K. Roy et al.

Summary: In the study on PKD patients, metabolomics analyses revealed metabolic disruptions including reduced late glycolysis, accumulation of PPP metabolites, oxidant stress, elevated hypoxia markers, and membrane lipid oxidation and remodeling. This study highlights the importance of basic science research in investigating pathologies in underrepresented minorities and aims to target treatments to health disparities more effectively.

FRONTIERS IN PHYSIOLOGY (2021)

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Article Hematology

The interactome of the N-terminus of band 3 regulates red blood cell metabolism and storage quality

Aaron Issaian et al.

Summary: AE1 plays a crucial role in regulating erythrocyte metabolism and storage quality, impacting red blood cell aging and storage. Dysfunction of AE1 results in oxidative imbalance, affecting blood quality and transfusion efficacy in donors.

HAEMATOLOGICA (2021)

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Article Hematology

Fatty acid desaturase activity in mature red blood cells and implications for blood storage quality

Tiffany Thomas et al.

Summary: The study found that fatty acid desaturases are present and active in mature RBCs, and their activity is sensitive to oxidant stress, storage duration, and alterations of the pyruvate/lactate ratio.

TRANSFUSION (2021)

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Article Hematology

Quantifying dynamic range in red blood cell energetics: Evidence of progressive energy failure during storage

Stephen C. Rogers et al.

Summary: During blood storage, red blood cells undergo significant metabolic and antioxidant changes which disrupt normal cellular processes and increase vulnerability to oxidative stress.

TRANSFUSION (2021)

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Article Biochemistry & Molecular Biology

Evaluation of the expression of red blood cell CD36, interleukin-6 and interleukin-8 in sickle cell anemia pediatric patients

Hanan Kifah Abdul-Hussein et al.

Summary: In patients with sickle cell anemia, levels of CD36, IL-6, and IL-8 are elevated during both crisis and steady state, with a positive correlation between IL-6 and neutrophils. These findings contribute to understanding the pathogenesis and treatment of the disease.

CYTOKINE (2021)

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Article Urology & Nephrology

Proteinuric chronic kidney disease is associated with altered red blood cell lifespan, deformability and metabolism

Rosi Bissinger et al.

Summary: This study using mouse models demonstrates the development of chronic kidney disease-associated anemia is linked to altered red blood cell metabolism, reduced RBC deformability, and enhanced cell death.

KIDNEY INTERNATIONAL (2021)

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Article Biochemistry & Molecular Biology

Erythrocyte adenosine A2B receptor prevents cognitive and auditory dysfunction by promoting hypoxic and metabolic reprogramming

Qingfen Qiang et al.

Summary: The lack of erythrocyte ADORA2B accelerates early onset of cognitive and hearing functional decline, as well as increases inflammatory response. The ADORA2B-BPGM axis in erythrocytes plays a key role in anti-aging and anti-age-related functional decline.

PLOS BIOLOGY (2021)

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Article Medicine, Research & Experimental

Hematologic and systemic metabolic alterations due to Mediterranean class II G6PD deficiency in mice

Angelo D'Alessandro et al.

Summary: G6PD deficiency is a common enzymopathy that may provide resistance to malaria, but also leads to hemolytic sequelae and is associated with various diseases. Generating a more accurate mouse model of G6PD deficiency has provided insights into altered metabolism and potential disease mechanisms.

JCI INSIGHT (2021)

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Article Cardiac & Cardiovascular Systems

Erythrocyte Metabolic Reprogramming by Sphingosine 1-Phosphate in Chronic Kidney Disease and Therapies

Tingting Xie et al.

CIRCULATION RESEARCH (2020)

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Article Medicine, Research & Experimental

Donor glucose-6-phosphate dehydrogenase deficiency decreases blood quality for transfusion

Richard O. Francis et al.

JOURNAL OF CLINICAL INVESTIGATION (2020)

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iMM1865: A New Reconstruction of Mouse Genome-Scale Metabolic Model

Saeideh Khodaee et al.

SCIENTIFIC REPORTS (2020)

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A consensus S. cerevisiae metabolic model Yeast8 and its ecosystem for comprehensively probing cellular metabolism

Hongzhong Lu et al.

NATURE COMMUNICATIONS (2019)

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Article Hematology

Effects of aged stored autologous red blood cells on human plasma metabolome

Angelo D'Alessandro et al.

BLOOD ADVANCES (2019)

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Systems biology as an emerging paradigm in transfusion medicine

James T. Yurkovich et al.

BMC SYSTEMS BIOLOGY (2018)

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Recon3D enables a three-dimensional view of gene variation in human metabolism

Elizabeth Brunk et al.

NATURE BIOTECHNOLOGY (2018)

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Review Biochemical Research Methods

Red blood cells as an organ? How deep omics characterization of the most abundant cell in the human body highlights other systemic metabolic functions beyond oxygen transport

Travis Nemkov et al.

EXPERT REVIEW OF PROTEOMICS (2018)

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Article Hematology

Methylation of protein aspartates and deamidated asparagines as a function of blood bank storage and oxidative stress in human red blood cells

Julie A. Reisz et al.

TRANSFUSION (2018)

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Citrate metabolism in red blood cells stored in additive solution-3

Angelo D'Alessandro et al.

TRANSFUSION (2017)

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Quantitative time-course metabolomics in human red blood cells reveal the temperature dependence of human metabolic networks

James T. Yurkovich et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2017)

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Quantitative Analysis of Human Red Blood Cell Proteome

Agata H. Bryk et al.

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Mfsd2b is essential for the sphingosine-1-phosphate export in erythrocytes and platelets

Thiet M. Vu et al.

NATURE (2017)

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Mannose and fructose metabolism in red blood cells during cold storage in SAGM

Ottar Rolfsson et al.

TRANSFUSION (2017)

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Structural and Functional Insight of Sphingosine 1-Phosphate-Mediated Pathogenic Metabolic Reprogramming in Sickle Cell Disease

Kaiqi Sun et al.

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Biomarkers are used to predict quantitative metabolite concentration profiles in human red blood cells

James T. Yurkovich et al.

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Aarash Bordbar et al.

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ATP11C is a major flippase in human erythrocytes and its defect causes congenital hemolytic anemia

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AltitudeOmics: Red Blood Cell Metabolic Adaptation to High Altitude Hypoxia

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Identified metabolic signature for assessing red blood cell unit quality is associated with endothelial damage markers and clinical outcomes

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