Influence of HINT-2 on Mitochondrial Protein Acetylation PDF Download

Author: Raviprasadh Rajasekaran
Publisher:
ISBN:
Category :
Languages : en
Pages : 169

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Author: Josue Baeza
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

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Reversible N-[epsilon]-acetylation has emerged as a widespread and regulatory modification throughout the cell. First identified on N-terminal histone tails over 50 years ago, acetylation has now been identified on over 36,000 lysine sites on organisms ranging from bacteria to mammals, highlighting the strong, conserved role for this modification. Acetylation is controlled by the opposing action of lysine acetyltransferases and deacetylases and recent evidence supports a role for nonenzymatic acetylation. Lysine acetylation influences many biochemical processes including: protein-protein and protein-DNA interactions, stability, cellular localization and enzymatic activity, which is thought to arise from neutralization of the positive charge on lysine residues at neutral pH. In mitochondria, acetylation generally acts as an inhibitory modification, altering protein interactions, lowered enzymatic activity and mislocalization of mitochondrial proteins. In this case, acetylation acts as a rheostat, modulating the degree of a biochemical process. Therefore, knowing the fraction of the protein that is modified, or stoichiometry, would provide critical information for understanding the regulatory effects of lysine acetylation. The mechanism of mitochondrial protein acetylation remains unknown. While there is a wealth of data supporting a dynamic and regulatory role for acetylation within mitochondria, there is very little evidence for an enzyme-catalyzed reaction. However, the conditions of the mitochondrial matrix: elevated acetyl-CoA levels and alkaline pH, raise the possibility that lysine acetylation can occur nonenzymatically. Throughout my thesis research, I have utilized chemical, biochemical, proteomic, and cellular studies to characterize protein acetylation. Specifically, I developed a mass spectrometry based approach to directly quantify lysine acetylation stoichiometry at the proteome-wide scale. Using this newly developed method, I measured the second order rate constants of nonenzymatic lysine acetylation using mitochondrial and non-mitochondrial proteins, highlighting the wide range of reactivities. The characterization of nonenzymatic rates of native protein demonstrates that the uncatalyzed reaction can account for the levels of acetylation in vivo. I also provide evidence that the majority of mitochondrial acetylation occurs within the mitochondria. Chapter 1 introduces lysine acetylation, the various processes controlling cellular levels including enzymatic and nonenzymatic, and why quantifying acetylation stoichiometry is needed. Chapter 2 discusses the mass spectrometry based method used for quantifying stoichiometry and its application in the model system, Escherichia coli. In chapter 3, I quantify the rates of nonenzymatic acetylation using a panel of mitochondrial and nonmitochondrial proteins, which highlights, for the first time, the wide range of lysine reactivities on native proteins. I then utilize an optimized version of the stoichiometry method to query mammalian lysine acetylation stoichiometry, revealing the wide distribution of acetylation across the cell. Conclusions, ongoing work, and future directions are presented in Chapter 5.

Author: Kunhua Song
Publisher: Frontiers Media SA
ISBN: 2889765563
Category : Medical
Languages : en
Pages : 158

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Author: John McMurry
Publisher: Roberts and Company Publishers
ISBN: 9780974707716
Category : Medical
Languages : en
Pages : 524

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Intended for advanced undergraduates and graduate students in all areas of biochemistry, The Organic Chemistry of Biological Pathways provides an accurate treatment of the major biochemical pathways from the perspective of mechanistic organic chemistry.

Author: Jacob Peedicayil
Publisher: Academic Press
ISBN: 0128235780
Category : Science
Languages : en
Pages : 848

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Epigenetics in Psychiatry, Second Edition covers all major areas of psychiatry in which extensive epigenetic research has been performed, fully encompassing a diverse and maturing field, including drug addiction, bipolar disorder, epidemiology, cognitive disorders, and the uses of putative epigenetic-based psychotropic drugs. Uniquely, each chapter correlates epigenetics with relevant advances across genomics, transcriptomics, and proteomics. The book acts as a catalyst for further research in this growing area of psychiatry. This new edition has been fully revised to address recent advances in epigenetic understanding of psychiatric disorders, evoking data consortia (e.g., CommonMind, ATAC-seq), single cell analysis, and epigenome-wide association studies to empower new research. The book also examines epigenetic effects of the microbiome on psychiatric disorders, and the use of neuroimaging in studying the role of epigenetic mechanisms of gene expression. Ongoing advances in epigenetic therapy are explored in-depth. Fully revised to discuss new areas of research across neuronal stem cells, cognitive disorders, and transgenerational epigenetics in psychiatric disease Relates broad advances in psychiatric epigenetics to a modern understanding of the genome, transcriptome, and proteins Catalyzes knowledge discovery in both basic epigenetic biology and epigenetic targets for drug discovery Provides guidance in research methods and protocols, as well how to employ data from consortia, single cell analysis, and epigenome-wide association studies (EWAS) Features chapter contributions from international leaders in the field

Author:
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Category : Carcinogenesis
Languages : en
Pages : 694

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Author:
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Category : Medicine
Languages : en
Pages : 1584

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Author: Thomas Seyfried
Publisher: John Wiley & Sons
ISBN: 1118310306
Category : Science
Languages : en
Pages : 482

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The book addresses controversies related to the origins of cancer and provides solutions to cancer management and prevention. It expands upon Otto Warburg's well-known theory that all cancer is a disease of energy metabolism. However, Warburg did not link his theory to the "hallmarks of cancer" and thus his theory was discredited. This book aims to provide evidence, through case studies, that cancer is primarily a metabolic disease requring metabolic solutions for its management and prevention. Support for this position is derived from critical assessment of current cancer theories. Brain cancer case studies are presented as a proof of principle for metabolic solutions to disease management, but similarities are drawn to other types of cancer, including breast and colon, due to the same cellular mutations that they demonstrate.

Author: Ralf Henkel
Publisher: Academic Press
ISBN: 0128125675
Category : Medical
Languages : en
Pages : 322

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Oxidants, Antioxidants and Impact of the Oxidative Status in Male Reproduction is an essential reference for fertility practitioners and research and laboratory professionals interested in learning about the role of reactive oxygen species in sperm physiology and pathology. The book focuses on unravelling the pathophysiology of oxidative stress mediated male infertility, recruiting top researchers and clinicians to contribute chapters. This collection of expertise delves into the physico-chemical aspects of oxidative stress, including a new focus on reductive stress. Furthermore, the inclusion of clinical techniques to determine oxidative stress and the OMICS of reductive oxidative stress are also included. This is a must-have reference in the area of oxidative stress and male reproductive function. Offers comprehensive information on oxidative stress and its role in male reproduction, including new therapeutic approaches Deals with current approaches to oxidative stress using OMICS platform“/li> Designed for fertility practitioners, reproductive researchers, and laboratory professionals interested in learning about the role of reactive oxygen species in sperm physiology and pathology

Author: Roger N. Rosenberg
Publisher: Elsevier
ISBN: 0124105491
Category : Science
Languages : en
Pages : 1465

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Rosenberg’s Molecular and Genetic Basis of Neurologic and Psychiatric Disease, Fifth Edition provides a comprehensive introduction and reference to the foundations and key practical aspects relevant to the majority of neurologic and psychiatric disease. A favorite of over three generations of students, clinicians and scholars, this new edition retains and expands the informative, concise and critical tone of the first edition. This is an essential reference for general medical practitioners, neurologists, psychiatrists, geneticists, and related professionals, and for the neuroscience and neurology research community. The content covers all aspects essential to the practice of neurogenetics to inform clinical diagnosis, treatment and genetic counseling. Every chapter has been thoroughly revised or newly commissioned to reflect the latest scientific and medical advances by an international team of leading scientists and clinicians. The contents have been expanded to include disorders for which a genetic basis has been recently identified, together with abundant original illustrations that convey and clarify the key points of the text in an attractive, didactic format. Previous editions have established this book as the leading tutorial reference on neurogenetics. Researchers will find great value in the coverage of genomics, animal models and diagnostic methods along with a better understanding of the clinical implications. Clinicians will rely on the coverage of the basic science of neurogenetics and the methods for evaluating patients with biochemical abnormalities or gene mutations, including links to genetic testing for specific diseases. Comprehensive coverage of the neurogenetic foundation of neurological and psychiatric disease Detailed introduction to both clinical and basic research implications of molecular and genetic understanding of the brain Detailed coverage of genomics, animal models and diagnostic methods with new coverage of evaluating patients with biochemical abnormalities or gene mutations