Gasotransmitters
Rui Wang, Rui Wang
- 301 pages
- English
- ePUB (mobile friendly)
- Available on iOS & Android
Gasotransmitters
Rui Wang, Rui Wang
About This Book
Gasotransmitters are gas molecules produced endogenously in prokaryotic and eukaryotic cells for signalling purposes. This book provides, for the first time, a comprehensive description and systematic look at all gasotransmitters, established or proposed, since their detection in 2002. The content and scope covers the production, metabolism, and signalling roles of gasotransmitters. Conceptual advances, scientific discoveries and newly developed techniques described in this book influence our understanding of fundamental molecular and cellular events in biology and medicine.
This book serves as the state-of-the-art book for undergraduate and graduate students as well as post-doctoral fellows in biomedical disciplines and toxicologists studying the toxic mechanisms of gasotransmitters in the environment. It will also be welcomed by researchers in university and research institutes, government agencies, pharmaceutical and medical instrument industry, and clinical practice.
Frequently asked questions
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1.1 Conceptualization and Evaluation Systems for Gasotransmitters
- Gasotransmitters are small molecules of gas. In sharp contrast to numerous endogenous substances, gasotransmitters exist in gaseous form or are dissolved in circulation, interstitial fluid, lymph, or intracellular fluid. This criterion is inclusive, rather than exclusive, to account for derivatives of primary gasotransmitters. Gasotransmitters must have a light molecular weight, but their derivatives can present a light or heavy molecular weight and may no longer be in gas state. Regardless, these derivatives are still part of the gasotransmitter family. The derivatives of NO, such as nitrite (NO2ā), nitrate (NO3ā), nitrous oxide (N2O), and nitroxyl (HNO), are examples of this inclusive concept of gasotransmitters. Together with persulfide, polysulfides are noticeable derivatives of H2S, playing important gasotransmitter functions for H2S or as H2S.5 These H2S derivatives also help buffer fluctuations in the H2S levels. Compared to endogenous H2S levels, the endogenous levels of polysulfides in cells and tissues are much higher. This is somehow related to the fact that polysulfide store and/or release H2S when needed.5 Polysulfides can be formed in different ways. Enzymatically, 3-mercaptopyruvate sulfur transfurase (MST) decomposes mercaptopyruvate into pyruvate and sulfur. While pyruvate is rapidly released, sulfur remains bound to MST and accumulates as non-diffusible polysulfides.6 After reaction of these polysulfides with thiols or sulfide, diffusible polysulfides may be consequently generated. The biological significance of this pathway is not clear as it relies on the cell type-specific expression of MST, and the diffusion and membrane permeability processes of the produced polysulfide are not straightforward. l-Cysteine competitively inhibits this pathway but mercaptoethanol activates it. The biogenesis of polysulfides can also stem from sulfide oxidation. One example of this path is the methemoglobin-dependent H2S oxidation, leading to the generation of thiosulfate and hydropolysulfides.7 Moreover, the interaction of H2S with NO or nitrosothiols through HSNO or after decomposition of SSNOā leads to the formation of polysulfides.8 It should be noted that our understanding of the biosynthetic pathways and functional impact, as well as the underlying molecular and chemical mechanisms of polysulfides is still very limited.Polysulfides can be reduced to sulfide in the presence of strong nucleophiles or enzymatically with the aid of the thioredoxin system or other enzymes. The endogenous conditions governing the bidirectional reactions between polysulfides and H2S remain still unclear. The elucidation of the conditions and further insight into the kinetics of these reactions will help solve the puzzle of whether the stronger cellular signaling effect of polysulfide compared to that of H2S at the same molar concentration is simply due to the fact that each polysulfide molecule contains multiple H2S molecules and to the fast kinetics of the polysulfide reduction to H2S. On the other hand, the polymerization of polysulfides affords cyclo-octasulfur (S8), and homolytic cleavage of polysulfides leads to the formation of sulfur radicals.Sulfur dioxide (SO2) is another derivative of H2S and its biological effects have been reported.9 NADPH oxidase, glutathione-dependent thiosulfate reductase, and thiosulfate sulfur transferase catalyze the oxidation of H2S to SO2.10ā12 In aqueous solution, sulfites may be formed by reaction of sulfide with O2 with formation of SO2ā¢ā and S2O42ā.13 Sulfur oxidation or sulfate reduction has been shown to generate SO2 in certain prokaryotes. Calcium-stimulated production of SO2 in porcine coronary arteries has been reported.14 Currently, the in vivo SO2 level is estimated using the proxy sulfite level. The sulfite level in rat plasma has been reported to range 10ā15 ĀµM.9
- Gasotransmitters are freely permeable to cellular membranes. As such, their intracellular and intercellular movements do not exclusively rely on cognate membrane receptors or other transportation machineries. Lipid bilayers are the structural skeleton of plasmalemma and the membrane of intracellular organelles. Other constituents of cellular membranes include phospholipids, cholesterol, glycolipids, and proteins. Depending on the type of cells and organs where the lipid bilaye...