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Physiology of blood
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2015
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
About 5% of glycolysis undergoes oxidation by the HMP shunt in which glucose-6-phosphate is converted to 6-phosphogluconate and to ribulose-5-phosphate. NADPH is formed from NADP, and this is linked with glutathione that maintains sulphydryl (-SH) groups intact in the cell. The amount of glucose passing through the HMP shunt is determined by the NADPH:NADP ratio.
Biology of microbes
Published in Philip A. Geis, Cosmetic Microbiology, 2006
Pentose phosphate pathway. The pentose phosphate pathway (also known as the hexose monophosphate pathway) uses a different set of reactions to form 3-, 4-, 5-, 6-, and 7-carbon sugar phosphates that are used to produce the ATP and NADPH (used in biosynthesis). The pathway is primarily used to provide the carbon skeletons for the synthesis of amino acids, nucleic acids, and other macromolecules. If biosynthesis is not needed, the NADPH will be converted to NADH to feed the electron transport chain for the production of more ATP. A unique reaction in this pathway is the production of 3-ribulose-5-phosphate from 6-phosphogluconate.
Microbial Pathways of Lipid A Biosynthesis
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Paul D. Rick, Christian R. H. Raetz
The synthesis of Kdo occurs as the result of three sequential reactions (92–94); these reactions are as follows: d-Ribulose-5-phosphate ⇄ d-Arabinose-5-phosphated-Arabinose-5-phosphate + Phosphoenolpyruvate → Kdo-8-phosphateKdo-8-phosphate → Kdo + Pi Reactions (a), (b), and (c) are catalyzed by the enzymes d-ribulose-5-phosphate isomerase, Kdo-8-phosphate synthetase, and Kdo-8-phosphate phosphatase, respectively. Free Kdo is then converted to CMP-Kdo, the nucleotide-sugar donor of Kdo residues for LPS synthesis, by the enzyme CTP:CMP-3-deoxy-d-manno-oc-tulosonate cytidylyltransferase (CMP-Kdo synthetase) (95). The synthesis of CMP-Kdo is somewhat unusual since prior activation of free Kdo by phosphorylation is not required, and the overall reaction is as follows: CTP + Kdo ⇄ CMP-Kdo + PPi The β-pyranose form of free Kdo is the preferred substrate for the CMP-Kdo synthetase, and the reaction proceeds by a mechanism that results in retention of the β-configuration in CMP-Kdo (96). The structural gene for CMP-Kdo synthetase (kdsB) is located at min 20.5 on the E. coli chromosome (97), and analysis of the nucleotide sequence of kdsB predicts that the enzyme consists of 248 amino acids and has a molecular weight of 27,486 daltons (98,99).
Functional signatures of ex-vivo dental caries onset
Published in Journal of Oral Microbiology, 2022
Dina G. Moussa, Ashok K. Sharma, Tamer A Mansour, Bruce Witthuhn, Jorge Perdigão, Joel D. Rudney, Conrado Aparicio, Andres Gomez
The upregulation of some metabolites along the glycolysis pathways is self-explanatory based on the fermentation of carbohydrates induced by bacterial metabolism. However, the depletion of Fumarate was an interesting finding that triggered our curiosity (Figure 7and Table 1). Fischbach and Sonnenburg systematically explained this phenomenon in the context of how anaerobic bacteria generate energy (ATP), maintain redox balance, and acquire carbon and nitrogen to synthesize primary metabolites [92]. They elucidated how Fumarate is key for anaerobic ATP synthesis in the final step of the primitive electron transport chain through its reduction to succinate, pointing to this metabolite as the most common terminal electron acceptor for anaerobic respiration [93]. Since biofilms were grown in an aerobic environment, as it happens with supragingival plaque in-vivo, excessive Fumarate consumption could be attributed to the presence of some strict anaerobic species within the microbial community – such as Veillonella (in WS_T1 and T2) and Fusobacterium (in WS_T2) – which strive to maintain their survival and energy production as aforementioned. Intriguingly, Ribulose-5-phosphate, also showed significant depletion at a later stage, when the lesions became overt (Figure 7and Table 1). The mechanisms behind depletion of this metabolite are unclear; however, ribulose-1,5-bisphosphate – the product of the phosphorylation of ribulose-5-phosphate- has been found to be the most important CO2 fixing pathway in prokaryotes, particularly around oxic/anoxic (free oxygen containing/free oxygen lacking) interfaces [94] that develop as a consequence of oxygen consumption [95]. Collectively, Ribulose-5-phosphate consumption seems to be also involved in bacterial adaptation mechanisms used for managing CO2 deficiency at an advanced stage of biofilm maturations.
Qingyi granules ameliorate severe acute pancreatitis in rats by modulating the gut microbiota and serum metabolic aberrations
Published in Pharmaceutical Biology, 2023
Juying Jiao, Jianjun Liu, Fei Luo, Mengxue Shang, Chen Pan, Bing Qi, Liang Zhao, Peiyuan Yin, Dong Shang
Intestinal microorganisms can cometabolize endogenous and exogenous substances to produce many absorbable metabolites that enter the host circulation and participate in host pathophysiological activities (Ye et al. 2021). Among the identified differentially abundant metabolites associated with SAP, α-linolenic acid, citric acid, succinic acid, galactaric acid, d-ribose 5-phosphate, hydrocinnamic acid and 3-indoxyl sulfate have been shown to have clinical importance in pancreatic and inflammatory diseases. α-Linolenic acid is an essential long-chain polyunsaturated fatty acid and has therapeutic value in metabolic syndrome, cancer, inflammation, oxidative stress, obesity, neuroprotection, and gut microbiota regulation (Yuan et al. 2022). The serum citric acid level in AP patients is significantly increased, with a higher level observed in SAP patients, indicating that it is a potential biomarker for AP (Xiao et al. 2017; Guo et al. 2019). Succinate, an intermediate in the Krebs cycle, can stabilize hypoxia-inducible factor-1 and stimulate dendritic cells to mediate inflammation (Mills and O'Neill 2014). It could promote IL-1β production in the inflammatory response (Tannahill et al. 2013). In addition, serum succinic acid levels were found to increase significantly in AP patients (Guo et al. 2019). Galactaric acid, a dicarboxylic acid produced by d-galacturonic acid oxidation, is closely involved in microflora metabolism (Watanabe et al. 2007). Serum galactaric acid was shown to be positively correlated with Ruminococcus abundance in hepatocellular carcinoma patients responding to immunotherapy (Wu et al. 2022). This suggests that high galactaric acid levels are related to abnormal microbiota activities in SAP. d-Ribose 5-phosphate is the end product of the PPP, and is produced by ribose-5-phosphate isomerase mediated isomerization of d-ribulose 5-phosphate (Chen et al. 2020). The increase in these two intermediates suggested enhancement of the PPP in SAP, which is supported by previous studies showing that PPP could be activated by lipopolysaccharide and that PPP inhibition could eliminate LPS-induced inflammatory cytokine secretion (Smith et al. 2014; Yu et al. 2019). Hydrocinnamic acid and 3-indoxyl sulfate are microbial metabolites. Hydrocinnamic acid is produced by Enterobacteriaceae, such as Escherichia coli (Sun et al. 2016; Sharma et al. 2019). It can act with PIP2 to trigger inflammation (Ren et al. 2017). 3-Indoxyl sulfate is a byproduct of indole metabolism by commensal gut bacteria and can induce intestinal barrier injury (Cheng et al. 2020). Mechanistically, indoxyl sulfate, as a kind of serotoxin, can induce oxidative stress to cause vascular damage and visceral dysfunction (Gao and Liu 2017).