Functions of the Liver
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
The breakdown of glucose to carbon dioxide and water with the production of energy is called glycolysis. Glucose catabolism proceeds by two pathways, either by cleavage to trioses producing pyruvic acid and lactic acid (the Embden–Meyerhof pathway) or via oxidation and decarboxylation to pentose (hexose monophosphate shunt). The net energy gain from glycolysis is three molecules of ATP. Pyruvic acid enters the citric acid cycle by conversion to acetic acid with the loss of one molecule of CO2. The citric acid cycle generates 12 molecules of ATP for every molecule of acetic acid. In total, 38 molecules of ATP are produced by the aerobic breakdown of glucose to pyruvate and its incorporation into the citric acid cycle. Pyruvic acid can be formed from the metabolism of amino acids and fat. Glycolysis produces acetyl CoA, which is used as a substrate for lipogenesis and subsequently the production of triglycerides. Another important property of the liver is the formation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) via the pentose phosphate pathway. Two NADPH molecules and ribose-5-phosphate are produced from one glucose molecule. NADPH is required for microsomal and mitochondrial hydroxylation of steroid hormones and biotransformation of many drugs.
Liver physiology
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2015
The breakdown of glucose to carbon dioxide and water with the production of energy is called glycolysis. Glucose catabolism proceeds by two pathways, either by cleavage to trioses producing pyruvic acid and lactic acid (the Embden–Meyerhorf pathway) or via oxidation and decarboxylation to pentose (hexose monophosphate shunt). The net energy gain from glycolysis is three molecules of ATP. Pyruvic acid enters the citric acid cycle by conversion to acetic acid with the loss of one molecule of CO2. The citric acid cycle generates 12 molecules of ATP for every molecule of acetic acid. In total, 38 molecules of ATP are produced by the aerobic breakdown of glucose to pyruvate and its incorporation into the citric acid cycle. Pyruvic acid can be formed from the metabolism of amino acids and fat. Glycolysis produces acetyl CoA, which is used as a substrate for lipogenesis and subsequently the production of triglycerides. Another important property of liver is the formation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) via the pentose phosphate pathway. Two NADPH molecules and ribose-5-phosphate are produced from one glucose molecule. NADPH is required for microsomal and mitochondrial hydroxylation of steroid hormones and biotransformation of many drugs.
Radioactivity and Radiotracers
Graham Lappin, Simon Temple in Radiotracers in Drug Development, 2006
14C is manufactured by neutron bombardment of 14N, usually in the form of beryllium nitride or aluminum nitride, resulting in 14CO2, typically stored as Ba14CO3. From here, a number of building blocks can be made, the most useful being carboxylic acids (particularly acetic acid), cyanide, methyl iodide and acetal-dehyde. Carboxylic acids are frequently brominated or chlorinated. From these basic building blocks, more complex radiolabeled molecules are synthesized. As an illustration, we will take two examples. Pyruvic acid, which is itself a precursor of more complex structures, can be made from a reaction of acetyl bromide with cyanide over a copper catalyst (Figure 2.5). There are three possible combinations of 14C-labeled reactants, each resulting in pyruvic acid labeled in a different carbon atom. If [U-14C]-pyruvic acid were required, then the three forms shown in Figure 2.5 would be mixed to provide a statistically uniform product, but no one molecule of pyruvic acid would be labeled in all three carbon atoms (see 2.8 regarding the relevance of this to specific activity).
Mitochondria as a key player in systemic lupus erythematosus
Published in Autoimmunity, 2022
Diana C. Quintero-González, Marcela Muñoz-Urbano, G. Vásquez
ATP production involves two processes with synergistic effects: glycolysis and oxidative phosphorylation (OXPHOS). Glucose is broken down and oxidized through glycolysis, resulting in four ATP molecules (two as net gain). Electrons released from glycolysis reduce nicotinamide adenine dinucleotide 1 (NAD1) to NADH1. Pyruvic acid, another product of glycolysis, enters the mitochondria in an oxygen-charged environment and is transformed into acetyl coenzyme A (CoA). CoA oxidation and other serial reactions in the Krebs cycle permit the generation of energy and compounds that carry hydrogen, including flavin adenine dinucleotide (FADH2) and NADH1 [13]. The OXPHOS reaction occurs in the electron transport chain (ETC), wherein hydrogen ions (H+) from NADH1/FADH2 on the MM are pumped to the intermembrane space through four respiratory complexes (in the order I, III, II, and IV), generating the mitochondrial transmembrane potential (MTP). Ultimately, the V complex, also known as ATP synthase, drives back the H+, leading to adenosine diphosphate phosphorylation and the formation of 34 ATP [14].
Repurposing metformin for covid-19 complications in patients with type 2 diabetes and insulin resistance
Published in Immunopharmacology and Immunotoxicology, 2021
Payam Hashemi, Shaghayegh Pezeshki
According to the investigations, glycolysis is the main metabolic pathway rather than mitochondrial pathway in inflammatory cells such as neutrophils, M1 macrophages, effector T cells, activated NK cells, and T helper 1, 17 [72,73]. Glycolysis can induce higher levels of inflammation due to more generation of ROS [74]. On the other hand, immunomodulatory cells such as M2 macrophages, regulatory and memory T cells are dependent on mitochondrial oxidation rather than glycolysis [72]. Electron transport chains of mitochondria have more ability to control oxidative stress of catalytic pathways compared with glycolysis [75–77]. Levels of mitochondrial oxidation of pyruvate (the main production of glycolysis) in inflammatory cells are lower than regulatory cells. So, inflammatory cells release more amounts of pyruvic acid into the circulation [78]. Generation of oxidative stress and inflammation in immune system is partially based on glycolysis [79]. Overactivity of immune system against the Covid-19 infection leads to damage of lung tissue including fibrosis, blood clots, endothelial dysfunction. These alternations may induce severe hypoxemia and ARDS in end stage of the infection [80].
Ethyl pyruvate ameliorates heat stroke-induced multiple organ dysfunction and inflammatory responses by induction of stress proteins and activation of autophagy in rats
Published in International Journal of Hyperthermia, 2021
Je-Ming Hu, Chih-Hsueng Hsu, Yu-Chun Lin, Ching-Wen Kung, Shu-Ying Chen, Wen-Ting Lin, Pao-Yun Cheng, Hsin-Hsueh Shen, Yen-Mei Lee
Ethyl pyruvate (EP), a derivative of pyruvic acid, has been shown to alleviate MOD and increase survival rate in many animal disease models, including sepsis, hemorrhagic shock and ischemia–reperfusion injury via exerting as a reactive oxygen species (ROS) scavenger and anti-inflammatory capacity [13,14]. Anti-inflammatory effects of EP are evidenced by the inhibition of NF-κB activation, resulting in the reduction of cytokine release, e.g., TNF-α, IL-1, IL-6 and high-mobility group box (HMGB) 1, as well as iNOS expression [15]. We have previously shown that EP possessed anticoagulant effects in lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) rat model and improvement of organ functions by reduction of IL-6 release and suppression of tissue factor expression. The protective effect of EP is associated with the induction of HO-1 expression [16]. Furthermore, EP attenuated liver injuries in several experimental animal models, including acute pancreatitis [17], alcohol, obstructive jaundice [18], ischemia–reperfusion [19], high-fat diet [20], as well as reduced acute fatal liver injury attributed from concanavalin A, d-galactosamine and acetaminophen [15]. However, the beneficial effect of EP on HS has not been investigated yet. In the present study, we explored the protective effect of EP on the MOD caused by HS in rats, and further investigated the possible mechanisms, including anti-inflammatory response, stress protein induction and activation of autophagy.
Related Knowledge Centers
- Carboxylic Acid
- Fatty Acid
- Glucose
- Ketone
- Metabolic Pathway
- Gluconeogenesis
- Carbohydrate
- Preferred Iupac Name
- Conjugate
- Glycolysis