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Beyond Enzyme Kinetics
Published in Clive R. Bagshaw, Biomolecular Kinetics, 2017
Oscillatory reactions are well known in inorganic chemistry, where the first discovered examples involved heterogeneous reactions in which the components were in different phases [90,268]. This physical separation of reactants contributed to the delay in feedback because of slow diffusion. Subsequently, oscillatory reactions were found in homogeneous solutions, where the inherent chemical kinetics gave rise to the delay in feedback. Oscillatory behavior is observed only over a narrow concentration range of specific components in which the mathematical solution to steady-state rate equations is a quadratic equation that has two real roots. Therefore, the concentrations of these intermediates show bistability and oscillate between these two solutions. Note that at least one of the components of the reaction must be far from equilibrium and is consumed during the reaction. Oscillations cease once this component drops below a critical concentration. Reactions that are approaching equilibrium do not oscillate. In the ABC reaction of Equation 2.30, the concentration of B initially rises and then falls, but it does not undergo repeated oscillations at the ensemble level. Biological clocks usually operate at the “systems” level. Oscillations have long been known within the glycolysis pathway [269]. Other well-characterized examples include the cyclin proteins, which are synthesized and degraded through regulated gene expression to control the cell cycle [51]. However, there is an example of a biological oscillator, which can be investigated using isolated purified proteins in vitro and modeled using the Law of Mass Action. The Kai proteins of the cyanobacterial circadian clock show spontaneous oscillations in the phosphorylation state within a near 24-hour period [270–276].
Temperature compensation and entrainment in cyanobacteria circadian rhythm
Published in Chronobiology International, 2023
Cyanobacteria are the simplest organisms to have circadian rhythms (Iwasaki and Kondo 2004). The cyanobacterial circadian clock is composed of two coupled components: a transcriptional/translational feedback loop (TTFL) and a post-translational oscillator (PTO). The key components of the circadian rhythms in cyanobacteria are KaiA, KaiB, and KaiC proteins (Ishiura et al. 1998). In TTFL, kaiBC mRNA transcribed by a single gene (kaiBC gene) is translated into KaiB and KaiC proteins (Ishiura et al. 1998); kaiBC gene expression is suppressed by phosphorylated KaiC (Nishiwaki et al. 2004). The negative feedback regulation of the kaiBC gene expression generates an autonomous oscillation, which is considered as a critical component for cyanobacteria rhythms (Ishiura et al. 1998). In PTO, the KaiC phosphorylation process are regulated by KaiA and KaiB proteins; KaiA promotes the phosphorylation of KaiC, and KaiB activates nonphosphorylation of (Iwasaki et al. 2002; Kitayama et al. 2003).
Efficacy and safety of Chinese patent medicine (Kang-ai injection) as an adjuvant in the treatment of patients with hepatocellular carcinoma: a meta-analysis
Published in Pharmaceutical Biology, 2021
Chuihua Sun, Fang Dong, Ting Xiao, Wenni Gao
Traditional Chinese medicine plays an increasingly important role in the treatment of several diseases, such as malaria, COVID-19 etc. (Tu 2016; Wang et al. 2018, 2020). KAI is a type of traditional Chinese medicine that has been clinically applied as an adjuvant therapy in HCC for decades (Song et al. 2014; Lu and Li 2018; Wan et al. 2018; Huang et al. 2019; Li et al. 2019). Although literature has reported the statistical analysis of published clinical trials, the exact therapeutic effect of KAI with regard to the treatment of HCC is yet to be evaluated systematically. Consequently, the present analysis performed an extensive online search, in accordance with strict inclusion and exclusion criteria, in order to arrive at clear and systematic conclusions.
Exploring the role of circadian clock gene and association with cancer pathophysiology
Published in Chronobiology International, 2020
Mahtab Keshvari, Mahdieh Nejadtaghi, Farnaz Hosseini-Beheshti, Ali Rastqar, Niraj Patel
It has even been proposed that this rhythmic phosphorylation itself might be a driving factor of circadian clocks. Up to this point, the transcription-translation negative feedback loop has been identified as the source of oscillations and rhythms in biological clocks. But, experiments with phosphorylation of the cyanobacterial protein KaiC in vitro showed that rhythms persisted without the presence of any transcription or translation (Nakajima et al. 2005). Therefore, kinases like dbt and CKIε might play even more important roles within circadian clocks than just targeting proteins for degradation.