scholarly journals Role of cytoplasmic thioltransferase in cellular regulation by thiol-disulphide interchange

1980 ◽  
Vol 190 (1) ◽  
pp. 125-130 ◽  
Author(s):  
B Mannervik ◽  
K Axelsson
Keyword(s):  
Pyruvate Kinase ◽  
Rat Liver ◽  
Protein Fraction ◽  
Cellular Regulation ◽  
General Role ◽  
Regulatory Processes ◽  
Glutathione Status ◽  
Glutathione Disulphide

Cytoplasmic thioltransferase purified from rat liver [Axelsson, Eriksson & Mannervik (1978) Biochemistry 17, 2978–2984] catalyses the formation and decomposition of mixed disulphides of proteins and glutathione. The enzyme was found to catalyse the reversible thiol-disulphide interchange between glutathione disulphide and a crude thiol-containing protein fraction from rat liver. This finding indicates a role of the thioltransferase in the regulation of the ‘glutathione status’ of the cell. Specifically, it was found that thioltransferase catalyses the reactivation of pyruvate kinase from rat liver that had previously been inactivated by glutathione disulphide. It is suggested that thioltransferase may have a general role in regulatory processes involving thiol-disulphide interchange.

scholarly journals Physiological concentrations of 2-oxoglutarate regulate the activity of phosphoenolpyruvate carboxykinase in liver

1992 ◽  
Vol 285 (3) ◽  
pp. 767-771 ◽  
Author(s):  
M A Titheradge ◽  
R A Picking ◽  
R C Haynes
Keyword(s):  
Pyruvate Kinase ◽  
Rat Liver ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Rat Hepatocytes ◽  
Fasted State ◽  
Stimulation Of

2-Oxoglutarate was found to inhibit purified rat liver phosphoenolpyruvate carboxykinase when the assay was performed in the direction of either phosphoenolpyruvate or oxaloacetate synthesis. The inhibition was competitive with respect to oxaloacetate or phosphoenolpyruvate, the Ki values being 0.32 +/- 0.04 mM 0.63 +/- 0.19 mM respectively. 2-Oxoglutarate inhibited non-competitively when tested against GTP or Mn2+. The reported cytosolic concentrations of 2-oxoglutarate in rat hepatocytes are such that the enzyme is likely to be significantly inhibited under basal conditions. The cytosolic concentration of 2-oxoglutarate is known to fall precipitously under the influence of glucagon and other hormones that stimulate gluconeogenesis, and it is suggested that the hormone-induced decrease in 2-oxoglutarate content would alleviate the inhibition of phosphoenolpyruvate carboxykinase and stimulate flux from oxaloacetate to phosphoenolpyruvate. The implications of this finding to the rationalization of the role of pyruvate kinase in the stimulation of gluconeogenesis in the fasted state are discussed.

scholarly journals The role of mitochondria in modifying calcium-sensitive cytoplasmic metabolic activities. Modification of pyruvate kinase activity

1972 ◽  
Vol 128 (2) ◽  
pp. 415-420 ◽  
Author(s):  
J. Meli ◽  
F. L. Bygrave
Keyword(s):  
Pyruvate Kinase ◽  
Rat Liver ◽  
Kinase Activity ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Pyruvate Kinase Activity ◽  
Metabolic Activities ◽  
The One

1. The modification of pyruvate kinase activity in vitro was examined by altering the environmental [Mg2+]/[Ca2+] ratio with EDTA on the one hand and isolated rat liver mitochondria on the other. 2. Controlled additions of Ca2+ and EDTA caused pyruvate kinase activity to be alternately and rapidly switched on and off. 3. By being able to accumulate Ca2+ in preference to Mg2+ rat liver mitochondria were able to alter the [Mg2+]/[Ca2+] ratio in the vicinity of pyruvate kinase and thereby modify the activity of this enzyme. 4. The possible role of mitochondria in modifying pyruvate kinase and other ion-sensitive cytoplasmic enzyme activities is discussed.

Sleep Problems During the Preschool Years and Beyond as a Marker of Risk and Resilience in Substance Use

2018 ◽  
Author(s):  
Maria M. Wong
Keyword(s):  
Substance Use ◽  
Alcohol Use ◽  
Sleep Problems ◽  
Problem Drinking ◽  
Alcohol Problems ◽  
Risk And Resilience ◽  
Regulatory Processes ◽  
Sleep Physiology ◽  
Before And After

Individuals with alcohol problems have well-described disturbances of sleep, but the development of these disturbances both before and after the onset of problem drinking is poorly understood. This chapter first discusses sleep physiology and its measurement in humans. It then examines the functions of sleep and its role in development. Next, it reviews recent research on the relationship between sleep and alcohol use and related problems. Whereas sleep problems (e.g., difficulties falling or staying asleep) increase the risk of early onset of alcohol use and related problems, sleep rhythmicity promotes resilience to the development of alcohol use disorder and problem substance use. Based on existing research, this chapter proposes a theoretical model of sleep and alcohol use, highlighting the role of self-regulatory processes as mediators of this relationship.

Dissent in the Atlantic World, 1787–1830

2018 ◽  
Author(s):  
Katherine Carté Engel
Keyword(s):  
United States ◽  
African Americans ◽  
First Amendment ◽  
Church And State ◽  
State Level ◽  
The United States ◽  
American Population ◽  
Simple Fact ◽  
General Role

The very term ‘Dissenter’ became problematic in the United States, following the passing of the First Amendment. The formal separation of Church and state embodied in the First Amendment was followed by the ending of state-level tax support for churches. None of the states established after 1792 had formal religious establishments. Baptists, Congregationalists, Presbyterians, and Methodists accounted for the majority of the American population both at the beginning and end of this period, but this simple fact masks an important compositional shift. While the denominations of Old Dissent declined relatively, Methodism grew quickly, representing a third of the population by 1850. Dissenters thus faced several different challenges. Primary among these were how to understand the idea of ‘denomination’ and also the more general role of institutional religion in a post-establishment society. Concerns about missions, and the positions of women and African Americans are best understood within this context.

From Organizations of Processes to Organisms and Other Biological Individuals

2018 ◽  
Author(s):  
Argyris Arnellos
Keyword(s):  
Multicellular Organism ◽  
Collaborative Networks ◽  
Biological Role ◽  
Regulatory Processes ◽  
Different Types ◽  
Organizational Framework

The emphasis on the collaborative dimension of life overlooks the importance of biological individuals (conceived of as integrated, self-maintaining organizations) in the build-up of more complex collaborative networks in the course of evolution. This chapter proposes a process-based organizational ontology for biology, according to which the essential features of unicellular organismicality are captured by a self-maintaining organization of processes integrated by means of a special type of collaboration (realized through regulatory processes entailing an indispensable interdependence) between its constitutive and its interactive aspects. This ontology is then used to describe different types of collaborations among cells and to suggest the type that yields a multicellular organism. The proposed organizational framework enables us to critically assess hypercollaborative views of life, especially issues related to the distinction between biological individuals and organisms and between life and non-life, without however underestimating the central biological role of collaboration.

scholarly journals Tethering-induced destabilization and ATP-binding for tandem RRM domains of ALS-causing TDP-43 and hnRNPA1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mei Dang ◽  
Yifan Li ◽  
Jianxing Song
Keyword(s):  
Conformational Dynamics ◽  
Md Simulations ◽  
Atp Binding ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Nucleic Acid Binding ◽  
General Role ◽  
Nmr Characterization ◽  
Lateral Sclerosis

AbstractTDP-43 and hnRNPA1 contain tandemly-tethered RNA-recognition-motif (RRM) domains, which not only functionally bind an array of nucleic acids, but also participate in aggregation/fibrillation, a pathological hallmark of various human diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), alzheimer's disease (AD) and Multisystem proteinopathy (MSP). Here, by DSF, NMR and MD simulations we systematically characterized stability, ATP-binding and conformational dynamics of TDP-43 and hnRNPA1 RRM domains in both tethered and isolated forms. The results reveal three key findings: (1) upon tethering TDP-43 RRM domains become dramatically coupled and destabilized with Tm reduced to only 49 °C. (2) ATP specifically binds TDP-43 and hnRNPA1 RRM domains, in which ATP occupies the similar pockets within the conserved nucleic-acid-binding surfaces, with the affinity slightly higher to the tethered than isolated forms. (3) MD simulations indicate that the tethered RRM domains of TDP-43 and hnRNPA1 have higher conformational dynamics than the isolated forms. Two RRM domains become coupled as shown by NMR characterization and analysis of inter-domain correlation motions. The study explains the long-standing puzzle that the tethered TDP-43 RRM1–RRM2 is particularly prone to aggregation/fibrillation, and underscores the general role of ATP in inhibiting aggregation/fibrillation of RRM-containing proteins. The results also rationalize the observation that the risk of aggregation-causing diseases increases with aging.

scholarly journals The Pleiotropic Function of Human Sirtuins as Modulators of Metabolic Pathways and Viral Infections

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 460
Author(s):  
Mohammed Hamed Alqarni ◽  
Ahmed Ibrahim Foudah ◽  
Magdy Mohamed Muharram ◽  
Nikolaos E. Labrou
Keyword(s):  
Metabolic Pathways ◽  
Histone Deacetylases ◽  
Viral Infections ◽  
Cell Physiology ◽  
Functional Roles ◽  
Regulatory Processes ◽  
Complex Functions ◽  
Natural Polyphenol ◽  
Antiviral Targets

Sirtuins (SIRTs) are nicotinamide adenine dinucleotide-dependent histone deacetylases that incorporate complex functions in the mechanisms of cell physiology. Mammals have seven distinct members of the SIRT family (SIRT1-7), which play an important role in a well-maintained network of metabolic pathways that control and adapt the cell to the environment, energy availability and cellular stress. Until recently, very few studies investigated the role of SIRTs in modulating viral infection and progeny. Recent studies have demonstrated that SIRT1 and SIRT2 are promising antiviral targets because of their specific connection to numerous metabolic and regulatory processes affected during infection. In the present review, we summarize some of the recent progress in SIRTs biochemistry and their emerging function as antiviral targets. We also discuss the potential of natural polyphenol-based SIRT modulators to control their functional roles in several diseases including viral infections.

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