Metabolism
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
The end product of glycolysis is pyruvate, which under aerobic conditions enters the citric acid cycle. Under aerobic conditions, the NADH + H+ formed by reaction ⑥ in Figure 65.3 is transferred indirectly to the mitochondrial electron transport chain to produce more ATP. This NADH + H+ from glycolysis in the cytoplasm is a charged molecule and cannot pass through the mitochondrial wall, but the electrons from the molecule can be transferred to any available NAD+ or FAD inside the mitochondria. (Under aerobic conditions, glycolysis can therefore continue, as NAD+ used up in reaction ⑥ is regenerated by this process.) Under anaerobic conditions, glycolysis can still continue, as two electrons can be transferred from NADH + H+ to pyruvate (to form lactate) to regenerate NAD+ and maintain reaction ⑥, although the process is less efficient in producing ATP than under aerobic conditions, and lactate is accumulated in the cell.
Carbohydrate supplementation
Jay R Hoffman in Dietary Supplementation in Sport and Exercise, 2019
Next in the process of glucose metabolism is the citric acid (TCA) cycle. Pyruvate molecules from glycolysis are transported into the mitochondria where they are first converted into acetyl-CoA and then fed into the pathway. A series of enzymatic reactions comprise the TCA cycle, where it produces three NADH+H, one FADH2 and one guanosine triphosphate (GTP) which is later converted to ATP. Following along in the oxidative metabolism of carbohydrates is the electron transport chain, which uses oxidative phosphorylation to produce ATP. This process is a series of coupled redox reactions that take advantage of the reducing capacity of NADH+H and FADH2. Briefly, these reducing agents donate electrons to the electron transport chain in order to generate a hydrogen ion gradient. The energy released from ions traveling down the concentration gradient helps to “power” ATP synthase to produce ATP. While the TCA cycle and the electron transport chain are able to produce large volumes of ATP molecules, the rate is significantly slower than glycolysis. When athletes are performing high work capacity events or performing exercise at a high intensity these two oxidative pathways are not able to keep up with energetic demands.
The Mannitol Enzyme II of the Bacterial Phosphotransferase System: A Functionally Chimaeric Protein with Receptor, Transport, Kinase, and Regulatory Activities
James F. Kane in Multifunctional Proteins: Catalytic/Structural and Regulatory, 2019
Figure 1 shows the pathway for the initiation of D-mannitol catabolism in E. coli. The sugar is transported across the membrane and concomitantly phosphorylated by a PTS-mediated mechanism. In this process the phosphoryl group of phosphoenolpyruvate is transferred sequentially from phosphoenolpyruvate to Enzyme I and HPr, the two energy coupling proteins of the phosphotransferase system. Phospho-HPr then binds to the cytoplasmic surface of the Enzyme II,Mtl and free mannitol, in the extracellular medium, approaches the sugar binding site on the outer face of the enzyme. Group translocation of the sugar through the membrane corresponds to the simultaneous transport and phosphorylation of the substrate, with the release of D-mannitol-1-phosphate in the cytoplasm. The byproduct of this reaction is pyruvate. Cytoplasmic mannitol-1-phosphate is then oxidized to fructose-6-phosphate in a process catalyzed by mannitol-1-phosphate dehydrogenase in which NAD+ serves as the electron acceptor. While the general energy coupling proteins of the PTS, Enzyme I, and HPr, are coded for by the ptsl and ptsH genes, respectively, which comprise the pts operon,9,10 the Enzyme IIMtl and the mannitol-1-phosphate dehydrogenase are coded for by the mtlA and mtlD genes, respectively, which comprise the mtl operon.11,12,13 Substantial differences between the protein constituents of the PTS in the two principal organisms under study, E. coli and S. typhimurium, have not been revealed by available investigations.
Ethyl pyruvate attenuates cisplatin-induced ovarian injury in rats via activating Nrf2 pathway
Published in Drug and Chemical Toxicology, 2023
Selim Demir, Ahmet Mentese, Hatice Kucuk, Esin Yulug, Nihal Turkmen Alemdar, Elif Ayazoglu Demir, Yuksel Aliyazicioglu
Pyruvate is both a product of glycolysis and a substrate molecule for the Krebs cycle, and is also an effective reactive oxygen species (ROS) scavenger (Ayazoglu Demir et al.2021). Solubility problem of pyruvate and its potential to form toxic intermediate metabolites limit its therapeutic potential (Yang et al.2016). Ethyl pyruvate (EP) has been therefore developed, which does not have the disadvantages of pyruvate (Wang et al.2014). The use of EP in the food and pharmaceutical industries is increased every year (Koprivica et al.2022). It has been shown to have antioxidant, anti-inflammatory, immunomodulator, anti-apoptotic, antitumoral, cardioprotective, neuroprotective, hepatoprotective and renoprotective activities (Yang et al.2016, Koprivica et al.2022). Although EP has been shown to abolish chemotherapeutic-induced tissue damage in various experimental models (Kelle et al.2014, Najafi et al.2016, Bakhtiary et al.2020, Ayral and Toprak 2021), there is no research on its effect on CDDP-induced ovotoxicity. It was therefore aimed to evaluate the therapeutic effect of EP against CDDP-induced ovarian damage for the first time in this study.
Cross talk between exosomes and pancreatic β-cells in diabetes
Published in Archives of Physiology and Biochemistry, 2022
The main function of the β-cells is the regulation of glucose metabolism, which is essential for coupling glucose sensing to insulin release, and glucose-stimulated insulin secretion (GSIS) is the best functional characteristic of mature β-cells (Salinno et al.2019) (Figure 2). After glucose enters β-cells through glucose transporters, it is quickly phosphorylated into glucose-6-phosphate (G6P) by glucokinase (GK) (Christensen and Gannon 2019). G6P is then metabolised through glycolysis to generate pyruvate, nicotinamide adenine dinucleotide, and adenosine triphosphate (ATP). Pyruvate, which subsequently enters the mitochondria, goes through the citric acid cycle and the electron transport chain to produce ATP with reactive oxygen species (ROS) as byproducts (Maechler 2013). The increase in the ATP/ADP ratio in the cell induces the closure of the KATP channels, leading to membrane depolarisation, and triggers the action potential that opens the voltage-gated Ca2+ channels. Finally, the influx of Ca2+ induces insulin secretion (Prentki and Nolan 2006). It should be noted that the expression of GK and the glucose transporter 2 (GLUT2) is strongly and positively related to the state of differentiation of β-cells, and both are under regulatory control of duodenal homeobox protein 1 (PDX1) (Lebrun et al.2005). Accordingly, PDX1 plays a key role both in promoting β-cell growth and enhancing β-cell function (Prentki and Nolan 2006).
Dimensions of inflammation in host defense and diseases
Published in International Reviews of Immunology, 2022
In mammals, lactate is a metabolic by-product of anaerobic respiration, a glycolytic pathway that ensures quick energy replenishment in the form of adenosine triphosphate (ATP) for the cells and prevention of muscle fatigue. Lactate acts as a circulating fuel in the blood that goes to the liver and is converted into pyruvate by the enzyme lactate dehydrogenase. Pyruvate is then converted into glucose via a metabolic pathway known as gluconeogenesis in the liver. Notably, lactate production increases when demand for ATP increases. In the past three decades, lactate has also been proved to be a very important signaling molecule that regulates various signaling pathways including inflammation-associated immune pathways. In this special issue, Zhou et al. [1] and Luo et al. [2] shed light on how endogenous lactate regulates inflammation in various immunological events, such as via macrophage polarization, T-cell immune dysfunction and its link with infectious and noninfectious diseases such as tumors. These two articles will be of interest to a broad readership in the field of immunology, as well as researchers investigating metaflammation and immunometabolic disorders and those in associated fields (Figure 1).
Related Knowledge Centers
- Carboxylic Acid
- Fatty Acid
- Glucose
- Ketone
- Metabolic Pathway
- Gluconeogenesis
- Carbohydrate
- Preferred Iupac Name
- Conjugate
- Glycolysis