Metabolism, nutrition, exercise and temperature regulation
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2015
The distinct reactions that occur in gluconeogenesis include the hydrolytic reactions converting glucose-6-phosphate to glucose (catalysed by glucose-6-phosphatase) and fructose-1–6-diphosphate to fructose-6-phosphate and the conversion of pyruvate to phosphoenolpyruvate (Figure 12.14). The conversion of pyruvate to phosphoenolpyruvate occurs in two separate reactions that require the enzymes pyruvate carboxylase and phosphoenolpyruvate carboxykinase. Pyruvate carboxylase enhances the conversion of pyruvate to oxaloacetate, which is then converted to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase. The gluconeogenetic enzymes are present in the cytoplasm of cells, except pyruvate carboxylase, which is present in mitochondria.
Potential of Diet and Dietary Supplementation to Ameliorate the Chronic Clinical Perturbations of Metabolic Syndrome
Stephen T. Sinatra, Mark C. Houston in Nutritional and Integrative Strategies in Cardiovascular Medicine, 2015
McCarty wrote an interesting article in the Journal Medical Hypotheses.156 On the basis of the earlier work, he hypothesized that biotin enhances glucokinase activity, which has a key role for normal glucose-stimulated insulin secretion, postprandial hepatic glucose uptake, and the appropriate suppression of hepatic glucose output and gluconeogenesis by elevated plasma glucose levels. Secondary effects on pyruvate kinase and phosphoenolpyruvate carboxykinase lowered hepatic glucose output. Suffice it to say, biotin decreases hepatic glucose production and output, as the drug metformin. Of interest, biguanides like metformin that have similar effects on hepatic output of glucose, have been shown to increase longevity in rodents.251,252 Could biotin mimic this effect in humans?
The Negative Acute Phase Proteins
Andrzej Mackiewicz, Irving Kushner, Heinz Baumann in Acute Phase Proteins, 2020
The changes in mRNA levels after partial hepatectomy for the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (increased to 3.5 times the normal level) and the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (reduced to one third of the normal level) were very large compared with those observed after induction of inflammation (Figure 11A). Changes in the transcriptional activity of the phosphoenolpyruvate carboxykinase gene in regenerating liver were sufficient to account for the changes observed in the mRNA level.43 The directions of change in the mRNA levels of glyceraldehyde-3-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase were unexpected, consistent with favoring glucose degradation over gluconeogenesis. However, the regenerating liver is predominantly a gluconeogenic organ.44,45 Increased phosphoenolpyruvate carboxykinase mRNA levels 1 to 4 h after partial hepatectomy have been reported.46 Phosphoenolpyruvate carboxykinase enzyme activity is increased during liver regeneration,43,45 maintaining the gluconeogenic nature of regenerating liver, despite decreased expression of the phospho-enolypyruvate carboxykinase gene.
Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors
Published in Drug Delivery, 2021
Xianhu Zeng, Zhipeng Li, Chunrong Zhu, Lisa Xu, Yong Sun, Shangcong Han
Gluconeogenesis can generate free glucose from non-carbohydrate carbon substrates (such as glycerol, lactic acid, pyruvate, and glycogenic amino acids). Although it is less studied than catabolic glycolysis or oxidative phosphorylation (OXPHOS), this anabolic pathway plays the same role in controlling the aerobic glycolysis of cancer cells (Seenappa et al. 2016). The complete pathway consists of 11 enzyme-catalyzed reactions, of which there are 7 reactions that are the opposite steps of glycolysis, and 3 reactions that are not involved in gluconeogenesis: (i) the conversion of pyruvate to phosphoenolpyruvate, which is determined by the reaction that catalyzes pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK); (ii) the catalyzation of the conversion of fructose-1,6-diphosphate to fructose-6-phosphate by fructose-1,6-bisphosphatase (FBPase); (iii) the catalyzation of the conversion of glucose-6-phosphate to glucose by glucose-6-phosphatase (G6Pase) (Icard et al. 2019). PEPCK, FBPase, and G6Pase are the key enzymes that control the gluconeogenesis flux, thereby affecting glycolysis, the TCA cycle, the PPP and other branched metabolic pathways (serine biosynthesis, glycogen health, gluconeogenesis, and glutamine decomposition) (Kang et al. 2016; Icard et al. 2019).
Experience and activity-dependent control of glucocorticoid receptors during the stress response in large-scale brain networks
Published in Stress, 2021
Damien Huzard, Virginie Rappeneau, Onno C. Meijer, Chadi Touma, Margarita Arango-Lievano, Michael J. Garabedian, Freddy Jeanneteau
Intracellular calcium (Ca2+) is a central mediator of transcriptional regulation and is controlled by neuronal activity that could gate GR and MR responsiveness either through the direct or indirect mode of transcriptional regulation (Zhang et al., 2009). Several phosphatases, proteases, and cargo transporters operating as Ca2+-sensors are involved in the response to glucocorticoids in multiple cellular compartments. Actions on synaptic neurotransmission and on nuclear gene transcription, which are mediated by GR and MR, require coincident Ca2+ mobilization from the mitochondria and the endoplasmic reticulum (Chameau et al., 2007; Harris et al., 2019; Mayanagi et al., 2008; Simard et al., 1999). Mobilization of Ca2+ and cAMP are both required for the nuclear import of the CREB-regulated transcription coactivators (CRTC1/2/3), a family of cofactors for CREB and GR (Altarejos & Montminy, 2011; Hill et al., 2016). In particular, CRTC2 can integrate BDNF and glucocorticoid signals in the hypothalamus to control the direction and magnitude of transcription at the corticotropin-releasing hormone (Crh) promoter and the response of the hypothalamic-pituitary-adrenocortical (HPA) axis to stressors (Jeanneteau et al., 2012). This molecular pathway also regulates glucose metabolism and the energetic adaptation to stress by controlling the expression of the rate-limiting enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver (Hill et al., 2016).
Impacts of high-sucrose diet on circadian rhythms in the small intestine of rats
Published in Chronobiology International, 2019
Shumin Sun, Fumiaki Hanzawa, Miki Umeki, Yasuko Matsuyama, Naomichi Nishimura, Saiko Ikeda, Satoshi Mochizuki, Hiroaki Oda
After being transported into epithelial cells, the sucrose-derived monosaccharides, glucose and fructose, are metabolized via different pathways. Recently, Jang et al. found that a limited amount of fructose is catabolized completely by the small intestine and gut bacteria, while high doses of fructose still spill over into the liver to be metabolized (Jang et al. 2018). Our results showed that expression of KHK (ketohexokinase) showed little changes in response to the high-sucrose diet (Figure 3i, Supplementary Table S2). Several rate-limiting enzymes of glycolysis, such as GCK (glucokinase), PFKL (phosphofructokinase), and PKLR (pyruvate kinase), exhibited little alteration in gene expression oscillations between the groups (Figure 3j–l, Supplementary Table S2), while expression of G6PC (glucose-6-phosphatase, catalytic subunit) and FBP1 (fructose-1, 6-bisphosphatase), which play important roles in gluconeogenesis, significantly increased in response to the high-sucrose diet (Figure 3m and n, Supplementary Table S2). As expression of PEPCK (phosphoenolpyruvate carboxykinase) did not change (Figure 3o, Supplementary Table S2) in response to the high-sucrose diet, gluconeogenesis from non-carbohydrate molecules was likely not increased. However, the small intestine may have worked to convert fructose metabolite, such as dihydroxyacetone phosphate and glyceraldehyde, into glucose.
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