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Essays in Biochemistry

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https://www.readbyqxmd.com/read/28550046/genome-instability-a-conserved-mechanism-of-ageing
#1
REVIEW
Jan Vijg, Xiao Dong, Brandon Milholland, Lei Zhang
DNA is the carrier of genetic information and the primary template from which all cellular information is ultimately derived. Changes in the DNA information content through mutation generate diversity for evolution through natural selection but are also a source of deleterious effects. It has since long been hypothesized that mutation accumulation in somatic cells of multicellular organisms could causally contribute to age-related cellular degeneration and death. Assays to detect different types of mutations, from base substitutions to large chromosomal aberrations, have been developed and show unequivocally that mutations accumulate in different tissues and cell types of ageing humans and animals...
May 26, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28539486/how-and-why-do-toxic-conformers-of-aberrant-proteins-accumulate-during-ageing
#2
REVIEW
Rebecca Josefson, Rebecca Andersson, Thomas Nyström
Ageing can be defined as a gradual decline in cellular and physical functions accompanied by an increased sensitivity to the environment and risk of death. The increased risk of mortality is causally connected to a gradual, intracellular accumulation of so-called ageing factors, of which damaged and aggregated proteins are believed to be one. Such aggregated proteins also contribute to several age-related neurodegenerative disorders e.g. Alzheimer's, Parkinson's, and Huntington's diseases, highlighting the importance of protein quality control (PQC) in ageing and its associated diseases...
May 24, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28698312/approaches-for-extending-human-healthspan-from-antioxidants-to-healthspan-pharmacology
#3
REVIEW
Jan Gruber, Barry Halliwell
Dramatic increases in human lifespan and declining population growth are monumental achievements but these same achievements have also led to many societies today ageing at a faster rate than ever before. Extending healthy lifespan (healthspan) is a key translational challenge in this context. Disease-centric approaches to manage population ageing risk are adding years to life without adding health to these years. The growing consensus that ageing is driven by a limited number of interconnected processes suggests an alternative approach...
July 15, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28698311/proteomics-and-metabolomics-in-ageing-research-from-biomarkers-to-systems-biology
#4
REVIEW
Jessica M Hoffman, Yang Lyu, Scott D Pletcher, Daniel E L Promislow
Age is the single greatest risk factor for a wide range of diseases, and as the mean age of human populations grows steadily older, the impact of this risk factor grows as well. Laboratory studies on the basic biology of ageing have shed light on numerous genetic pathways that have strong effects on lifespan. However, we still do not know the degree to which the pathways that affect ageing in the lab also influence variation in rates of ageing and age-related disease in human populations. Similarly, despite considerable effort, we have yet to identify reliable and reproducible 'biomarkers', which are predictors of one's biological as opposed to chronological age...
July 15, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28698310/systems-modelling-ageing-from-single-senescent-cells-to-simple-multi-cellular-models
#5
REVIEW
Alvaro Martinez Guimera, Ciaran Welsh, Piero Dalle Pezze, Nicola Fullard, Glyn Nelson, Mathilde F Roger, Stefan A Przyborski, Daryl P Shanley
Systems modelling has been successfully used to investigate several key molecular mechanisms of ageing. Modelling frameworks to allow integration of models and methods to enhance confidence in models are now well established. In this article, we discuss these issues and work through the process of building an integrated model for cellular senescence as a single cell and in a simple tissue context.
July 15, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28698309/differential-control-of-ageing-and-lifespan-by-isoforms-and-splice-variants-across-the-mtor-network
#6
REVIEW
Patricia Razquin Navas, Kathrin Thedieck
Ageing can be defined as the gradual deterioration of physiological functions, increasing the incidence of age-related disorders and the probability of death. Therefore, the term ageing not only reflects the lifespan of an organism but also refers to progressive functional impairment and disease. The nutrient-sensing kinase mTOR (mammalian target of rapamycin) is a major determinant of ageing. mTOR promotes cell growth and controls central metabolic pathways including protein biosynthesis, autophagy and glucose and lipid homoeostasis...
July 15, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28698308/the-role-of-attenuated-redox-and-heat-shock-protein-responses-in-the-age-related-decline-in-skeletal-muscle-mass-and-function
#7
REVIEW
Anne McArdle, Malcolm J Jackson
The loss of muscle mass and weakness that accompanies ageing is a major contributor to physical frailty and loss of independence in older people. A failure of muscle to adapt to physiological stresses such as exercise is seen with ageing and disruption of redox regulated processes and stress responses are recognized to play important roles in theses deficits. The role of redox regulation in control of specific stress responses, including the generation of heat shock proteins (HSPs) by muscle appears to be particularly important and affected by ageing...
July 15, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28698307/origins-of-mtdna-mutations-in-ageing
#8
REVIEW
Karolina Szczepanowska, Aleksandra Trifunovic
MtDNA mutations are one of the hallmarks of ageing and age-related diseases. It is well established that somatic point mutations accumulate in mtDNA of multiple organs and tissues with increasing age and heteroplasmy is universal in mammals. However, the origin of these mutations remains controversial. The long-lasting hypothesis stating that mtDNA mutations emanate from oxidative damage via a self-perpetuating mechanism has been extensively challenged in recent years. Contrary to this initial ascertainment, mtDNA appears to be well protected from action of reactive oxygen species (ROS) through robust protein coating and endomitochondrial microcompartmentalization...
July 15, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28487405/quantum-chemical-approaches-to-nife-hydrogenase
#9
REVIEW
Valerie Vaissier, Troy Van Voorhis
The mechanism by which [NiFe] hydrogenase catalyses the oxidation of molecular hydrogen is a significant yet challenging topic in bioinorganic chemistry. With far-reaching applications in renewable energy and carbon mitigation, significant effort has been invested in the study of these complexes. In particular, computational approaches offer a unique perspective on how this enzyme functions at an electronic and atomistic level. In this article, we discuss state-of-the art quantum chemical methods and how they have helped deepen our comprehension of [NiFe] hydrogenase...
May 9, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28487404/long-range-proton-coupled-electron-transfer-in-the-escherichia-coli-class-ia-ribonucleotide-reductase
#10
REVIEW
Steven Y Reece, Mohammad R Seyedsayamdost
Escherichia coli class Ia ribonucleotide reductase (RNR) catalyzes the conversion of nucleotides to 2'-deoxynucleotides using a radical mechanism. Each turnover requires radical transfer from an assembled diferric tyrosyl radical (Y•) cofactor to the enzyme active site over 35 Å away. This unprecedented reaction occurs via an amino acid radical hopping pathway spanning two protein subunits. To study the mechanism of radical transport in RNR, a suite of biochemical approaches have been developed, such as site-directed incorporation of unnatural amino acids with altered electronic properties and photochemical generation of radical intermediates...
May 9, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28487403/cluster-assembly-in-nitrogenase
#11
REVIEW
Nathaniel S Sickerman, Lee A Rettberg, Chi Chung Lee, Yilin Hu, Markus W Ribbe
The versatile enzyme system nitrogenase accomplishes the challenging reduction of N2and other substrates through the use of two main metalloclusters. For molybdenum nitrogenase, the catalytic component NifDK contains the [Fe8S7]-core P-cluster and a [MoFe7S9C-homocitrate] cofactor called the M-cluster. These chemically unprecedented metalloclusters play a critical role in the reduction of N2, and both originate from [Fe4S4] clusters produced by the actions of NifS and NifU. Maturation of P-cluster begins with a pair of these [Fe4S4] clusters on NifDK called the P*-cluster...
May 9, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28487402/biological-functions-controlled-by-manganese-redox-changes-in-mononuclear-mn-dependent-enzymes
#12
REVIEW
Wen Zhu, Nigel G J Richards
Remarkably few enzymes are known to employ a mononuclear manganese ion that undergoes changes in redox state during catalysis. Many questions remain to be answered about the role of substrate binding and/or protein environment in modulating the redox properties of enzyme-bound Mn(II), the nature of the dioxygen species involved in the catalytic mechanism, and how these enzymes acquire Mn(II) given that many other metal ions in the cell form more stable protein complexes. Here, we summarize current knowledge concerning the structure and mechanism of five mononuclear manganese-dependent enzymes: superoxide dismutase, oxalate oxidase (OxOx), oxalate decarboxylase (OxDC), homoprotocatechuate 3,4-dioxygenase, and lipoxygenase (LOX)...
May 9, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28487401/repurposing-proteins-for-new-bioinorganic-functions
#13
REVIEW
Lewis A Churchfield, Athira George, F Akif Tezcan
Inspired by the remarkable sophistication and complexity of natural metalloproteins, the field of protein design and engineering has traditionally sought to understand and recapitulate the design principles that underlie the interplay between metals and protein scaffolds. Yet, some recent efforts in the field demonstrate that it is possible to create new metalloproteins with structural, functional and physico-chemical properties that transcend evolutionary boundaries. This essay aims to highlight some of these efforts and draw attention to the ever-expanding scope of bioinorganic chemistry and its new connections to synthetic biology, biotechnology, supramolecular chemistry and materials engineering...
May 9, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28487400/native-and-engineered-sensors-for-ca-2-and-zn-2-lessons-from-calmodulin-and-mtf1
#14
REVIEW
Margaret C Carpenter, Amy E Palmer
Ca(2+) and Zn(2+) dynamics have been identified as important drivers of physiological processes. In order for these dynamics to encode function, the cell must have sensors that transduce changes in metal concentration to specific downstream actions. Here we compare and contrast the native metal sensors: calmodulin (CaM), the quintessential Ca(2+) sensor and metal-responsive transcription factor 1 (MTF1), a candidate Zn(2+) sensor. While CaM recognizes and modulates the activity of hundreds of proteins through allosteric interactions, MTF1 recognizes a single DNA motif that is distributed throughout the genome regulating the transcription of many target genes...
May 9, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28487399/the-zinc-paradigm-for-metalloneurochemistry
#15
REVIEW
Chelsea A Barr, Shawn C Burdette
Neurotransmission and sensory perception are shaped through metal ion-protein interactions in various brain regions. The term "metalloneurochemistry" defines the unique field of bioinorganic chemistry focusing on these processes, and zinc has been the leading target of metalloneurochemists in the almost 15 years since the definition was introduced. Zinc in the hippocampus interacts with receptors that dictate ion flow and neurotransmitter release. Understanding the intricacies of these interactions is crucial to uncovering the role that zinc plays in learning and memory...
May 9, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28487398/transition-metals-at-the-host-pathogen-interface-how-neisseria-exploit-human-metalloproteins-for-acquiring-iron-and-zinc
#16
REVIEW
Wilma Neumann, Rose C Hadley, Elizabeth M Nolan
Transition metals are essential nutrients for all organisms and important players in the host-microbe interaction. During bacterial infection, a tug-of-war between the host and microbe for nutrient metals occurs: the host innate immune system responds to the pathogen by reducing metal availability and the pathogen tries to outmaneuver this response. The outcome of this competition, which involves metal-sequestering host-defense proteins and microbial metal acquisition machinery, is an important determinant for whether infection occurs...
May 9, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28487397/ion-channels-and-ion-selectivity
#17
REVIEW
Benoît Roux
Specific macromolecular transport systems, ion channels and pumps, provide the pathways to facilitate and control the passage of ions across the lipid membrane. Ion channels provide energetically favourable passage for ions to diffuse rapidly and passively according to their electrochemical potential. Selective ion channels are essential for the excitability of biological membranes: the action potential is a transient phenomenon that reflects the rapid opening and closing of voltage-dependent Na(+)-selective and K(+)-selective channels...
May 9, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28487396/metallochaperones-and-metalloregulation-in-bacteria
#18
REVIEW
Daiana A Capdevila, Katherine A Edmonds, David P Giedroc
Bacterial transition metal homoeostasis or simply 'metallostasis' describes the process by which cells control the intracellular availability of functionally required metal cofactors, from manganese (Mn) to zinc (Zn), avoiding both metal deprivation and toxicity. Metallostasis is an emerging aspect of the vertebrate host-pathogen interface that is defined by a 'tug-of-war' for biologically essential metals and provides the motivation for much recent work in this area. The host employs a number of strategies to starve the microbial pathogen of essential metals, while for others attempts to limit bacterial infections by leveraging highly competitive metals...
May 9, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28258239/the-pushmi-pullyu-of-resistance-to-chloroquine-in-malaria
#19
REVIEW
Ruth Skrzypek, Richard Callaghan
Malarial infection continues to impart devastating health problems in the developing world. Treatment of malaria has involved chemotherapy since 168 BC, with the most prevalent and successful forms using plant alkaloids. Perhaps the greatest treatment success against malaria was by chloroquine, a synthetic derivative of the quinines found in the Cinchona tree bark. Chloroquine is able to kill parasites by interfering with haem metabolism in the parasite's digestive vacuole. The widespread use of chloroquine predictably resulted in the development of drug-resistant malaria and the most highly implicated resistance mediators are the transporter proteins P-glycoprotein (P-gp) homologue 1 (P-gh1) and Plasmodium falciparum chloroquine-resistance transporter (PfCRT), which reside on the parasite's digestive vacuole...
February 28, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28258238/resistance-to-antifungal-therapies
#20
REVIEW
Rajendra Prasad, Atanu Banerjee, Abdul Haseeb Shah
The evolution of antifungal resistance among fungal pathogens has rendered the limited arsenal of antifungal drugs futile. Considering the recent rise in the number of nosocomial fungal infections in immunocompromised patients, the emerging clinical multidrug resistance (MDR) has become a matter of grave concern for medical professionals. Despite advances in therapeutic interventions, it has not yet been possible to devise convincing strategies to combat antifungal resistance. Comprehensive understanding of the molecular mechanisms of antifungal resistance is essential for identification of novel targets that do not promote or delay emergence of drug resistance...
February 28, 2017: Essays in Biochemistry
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