scholarly journals Quantifying biochemical reaction rates from static population variability within complex networks

2021 ◽  
Author(s):  
Timon Wittenstein ◽  
Nava Leibovich ◽  
Andreas Hilfinger
Keyword(s):  
Reaction Rates ◽  
Population Variability ◽  
Biochemical Reaction ◽  
Cellular Processes ◽  
Inference Problems ◽  
Stochastic Fluctuations ◽  
Rate Functions ◽  
Qualitative Knowledge ◽  
Intractable Problem ◽  
Cell Data

Quantifying biochemical reaction rates within complex cellular processes remains a key challenge of systems biology even as high-throughput single-cell data have become available to characterize snapshots of population variability. That is because complex systems with stochastic and non-linear interactions are difficult to analyze when not all components can be observed simultaneously and systems cannot be followed over time. Instead of using descriptive statistical models, we show that incompletely specified mechanistic models can be used to translate qualitative knowledge of interactions into reaction rate functions from covariability data between pairs of components. This promises to turn a globally intractable problem into a sequence of solvable inference problems to quantify complex interaction networks from incomplete snapshots of their stochastic fluctuations.

scholarly journals Principles of RNA and nucleotide discrimination by the RNA processing enzyme RppH

2020 ◽  
Vol 48 (7) ◽  
pp. 3776-3788 ◽  
Author(s):  
Ang Gao ◽  
Nikita Vasilyev ◽  
Abhishek Kaushik ◽  
Wenqian Duan ◽  
Alexander Serganov
Keyword(s):  
Rna Processing ◽  
Reaction Rates ◽  
Growth Conditions ◽  
Rna Degradation ◽  
Nudix Hydrolase ◽  
X Ray ◽  
E Coli ◽  
Cellular Processes ◽  
Protein Factor ◽  
Hydrolysis Of

Abstract All enzymes face a challenge of discriminating cognate substrates from similar cellular compounds. Finding a correct substrate is especially difficult for the Escherichia coli Nudix hydrolase RppH, which triggers 5′-end-dependent RNA degradation by removing orthophosphate from the 5′-diphosphorylated transcripts. Here we show that RppH binds and slowly hydrolyzes NTPs, NDPs and (p)ppGpp, which each resemble the 5′-end of RNA. A series of X-ray crystal structures of RppH-nucleotide complexes, trapped in conformations either compatible or incompatible with hydrolysis, explain the low reaction rates of mononucleotides and suggest two distinct mechanisms for their hydrolysis. While RppH adopts the same catalytic arrangement with 5′-diphosphorylated nucleotides as with RNA, the enzyme hydrolyzes 5′-triphosphorylated nucleotides by extending the active site with an additional Mg2+ cation, which coordinates another reactive nucleophile. Although the average intracellular pH minimizes the hydrolysis of nucleotides by slowing their reaction with RppH, they nevertheless compete with RNA for binding and differentially inhibit the reactivity of RppH with triphosphorylated and diphosphorylated RNAs. Thus, E. coli RppH integrates various signals, such as competing non-cognate substrates and a stimulatory protein factor DapF, to achieve the differential degradation of transcripts involved in cellular processes important for the adaptation of bacteria to different growth conditions.

scholarly journals Linear conjugacy in biochemical reaction networks with rational reaction rates

2016 ◽  
Vol 54 (8) ◽  
pp. 1658-1676 ◽  
Author(s):  
Attila Gábor ◽  
Katalin M. Hangos ◽  
Gábor Szederkényi
Keyword(s):  
Reaction Rates ◽  
Biochemical Reaction ◽  
Reaction Networks ◽  
Biochemical Reaction Networks

scholarly journals The transcriptome dynamics of single cells during the cell cycle

2019 ◽  
Author(s):  
Daniel Schwabe ◽  
Sara Formichetti ◽  
Jan Philipp Junker ◽  
Martin Falcke ◽  
Nikolaus Rajewsky
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Design Principle ◽  
Single Cells ◽  
High Dimensional ◽  
Circular Trajectory ◽  
Cellular Processes ◽  
Cycling Gene ◽  
Third Dimension ◽  
Cell Data

AbstractDespite advances in single-cell data analysis, the dynamics and topology of the cell cycle in high-dimensional gene expression space remains largely unknown. Here, we use a linear analysis of transcriptome data to reveal that cells move along a circular trajectory in transcriptome space during the cell cycle. This movement occurs largely independently from other cellular processes. Non-cycling gene expression (changes in environment or epigenetic state) adds a third dimension and causes helical motion on a hollow cylinder. The circular trajectory shape indicates minimal acceleration of transcription, i.e. the cell cycle has evolved to minimize changes of transcriptional activity and its entailing regulatory effort. Thus, we uncover a general design principle of the cell cycle that may be of relevance to many other cellular differentiation processes.One Sentence SummaryCells traverse high-dimensional gene expression space in a 2D circular motion, thus minimizing changes of expression changes (“Acceleration”).

scholarly journals Regulation of biochemical reaction rates by flexible tethers

2011 ◽  
Vol 84 (2) ◽  
Author(s):  
Daniel Reeves ◽  
Keith Cheveralls ◽  
Jane Kondev
Keyword(s):  
Reaction Rates ◽  
Biochemical Reaction

scholarly journals Life's chirality from prebiotic environments

2012 ◽  
Vol 11 (4) ◽  
pp. 287-296 ◽  
Author(s):  
Marcelo Gleiser ◽  
Sara Imari Walker
Keyword(s):  
Chiral Symmetry Breaking ◽  
Enantiomeric Excess ◽  
Reaction Rates ◽  
Polymerization Reaction ◽  
Extraterrestrial Life ◽  
Representative Sampling ◽  
Stochastic Fluctuations ◽  
Environmental Events ◽  
Open Question

AbstractA key open question in the study of life is the origin of biomolecular homochirality: almost every life-form on Earth has exclusively levorotary amino acids and dextrorotary sugars. Will the same handedness be preferred if life is found elsewhere? We review some of the pertinent literature and discuss recent results suggesting that life's homochirality resulted from sequential chiral symmetry breaking triggered by environmental events. In one scenario, autocatalytic prebiotic reactions undergo stochastic fluctuations due to environmental disturbances, in a mechanism reminiscent of evolutionary punctuated equilibrium: short-lived destructive events may lead to long-term enantiomeric excess. In another, chiral-selective polymerization reaction rates influenced by environmental effects lead to substantial chiral excess even in the absence of autocatalysis. Applying these arguments to other potentially life-bearing platforms has implications to the search for extraterrestrial life: we predict that a statistically representative sampling of extraterrestrial stereochemistry will be racemic (chirally neutral) on average.

scholarly journals A self-regulating biomolecular comparator for processing oscillatory signals

2015 ◽  
Vol 12 (111) ◽  
pp. 20150586 ◽  
Author(s):  
Deepak K. Agrawal ◽  
Elisa Franco ◽  
Rebecca Schulman
Keyword(s):  
Conformational Changes ◽  
Reaction Rates ◽  
Electronic Systems ◽  
Signal Molecule ◽  
Square Wave ◽  
Precise Control ◽  
Cellular Processes ◽  
Downstream Processes

While many cellular processes are driven by biomolecular oscillators, precise control of a downstream on/off process by a biochemical oscillator signal can be difficult: over an oscillator's period, its output signal varies continuously between its amplitude limits and spends a significant fraction of the time at intermediate values between these limits. Further, the oscillator's output is often noisy, with particularly large variations in the amplitude. In electronic systems, an oscillating signal is generally processed by a downstream device such as a comparator that converts a potentially noisy oscillatory input into a square wave output that is predominantly in one of two well-defined on and off states. The comparator's output then controls downstream processes. We describe a method for constructing a synthetic biochemical device that likewise produces a square-wave-type biomolecular output for a variety of oscillatory inputs. The method relies on a separation of time scales between the slow rate of production of an oscillatory signal molecule and the fast rates of intermolecular binding and conformational changes. We show how to control the characteristics of the output by varying the concentrations of the species and the reaction rates. We then use this control to show how our approach could be applied to process different in vitro and in vivo biomolecular oscillators, including the p53-Mdm2 transcriptional oscillator and two types of in vitro transcriptional oscillators. These results demonstrate how modular biomolecular circuits could, in principle, be combined to build complex dynamical systems. The simplicity of our approach also suggests that natural molecular circuits may process some biomolecular oscillator outputs before they are applied downstream.

SEM analysis of the change in the reaction rates with deposit structures in the copper-iron cementation system

1978 ◽  
Vol 36 (1) ◽  
pp. 456-457
Author(s):  
V. Annamalai ◽  
L.E. Murr
Keyword(s):  
Structural Characteristics ◽  
Secondary Electron Emission ◽  
Copper Deposit ◽  
Reaction Rates ◽  
Sem Analysis ◽  
Experimental Conditions ◽  
Major Drawback ◽  
Emission Mode ◽  
Scrap Iron ◽  
Image Position

Economical recovery of copper metal from leach liquors has been carried out by the simple process of cementing copper onto a suitable substrate metal, such as scrap-iron, since the 16th century. The process has, however, a major drawback of consuming more iron than stoichiometrically needed by the reaction.Therefore, many research groups started looking into the process more closely. Though it is accepted that the structural characteristics of the resultant copper deposit cause changes in reaction rates for various experimental conditions, not many systems have been systematically investigated. This paper examines the deposit structures and the kinetic data, and explains the correlations between them.A simple cementation cell along with rotating discs of pure iron (99.9%) were employed in this study to obtain the kinetic results The resultant copper deposits were studied in a Hitachi Perkin-Elmer HHS-2R scanning electron microscope operated at 25kV in the secondary electron emission mode.

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