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Whole-Body Regulation of Energy Expenditure, Exercise Fuel Selection, and Dietary Recommendations
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Oxidative Phosphorylation: At rest or with exercise below the respiratory threshold (∼60%–70% V˙O2max), aerobic glycolysis predominates. Here, pyruvic acid enters the mitochondria rather than being reduced to lactic acid and is converted into acetyl-CoA by the action of the pyruvate dehydrogenase complex, making the electron carrier nicotinamide adenine dinucleotide (NADH) available, as it is not needed to form lactic acid. The acetyl-CoA enters the citric acid cycle, where additional NADH and another electron carrier (FADH2), CO2, and a small amount of ATP (substrate phosphorylation) are formed. Ultimately, these carriers pass electrons along the electron transport chain (ETC), also located within the mitochondria, resulting in ATP synthesis, utilizing O2, and forming H2O as an end product. Since the 1960s this electron carrier oxidation coupling to ATP synthesis (chemiosmotic theory; 42) has been the prevailing explanation underlying how oxidative phosphorylation works, but data are accumulating that the torsional theory may more accurately explain the detail of this key step in oxidative metabolism (2, 45). Finally, aerobic metabolism predominates at rest and with low-to-moderate exercise intensities until the rate of pyruvic acid formation from accelerated glycolysis exceeds its maximal removal rate as acetyl-CoA into the citric acid cycle, at which point anaerobic glycolysis ramps up and muscle lactic acid production increases rapidly.
Skeletal Muscle
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
In practically all body cells, the main source of ATP is the citric acid cycle, also known as the tricarboxylic acid cycle or the Krebs cycle, which can metabolize all forms of nutrients, that is, carbohydrates, fats, and proteins. The input to the cycle is from glycolysis, and the output feeds oxidative phosphorylation, which provides most of the ATP, using oxygen, ADP, and phosphate (Figure 9.7). Both the citric acid cycle and oxidative phosphorylation occur in the mitochondria. Glycolysis is the metabolic pathway that breaks down one glucose molecule into two pyruvate molecules, the ionized form of pyruvic acid, and occurs in the cytoplasm outside the mitochondria. Under aerobic conditions, that is in the presence of oxygen, pyruvate feeds into the citric acid cycle, but under anaerobic conditions, that is in the absence of oxygen, pyruvate is converted to lactate.
Metabolism
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
The citric acid cycle (Figure 65.10) is an important aerobic metabolic reaction within mitochondria as it provides reduced coenzymes required for the final phase, oxidative phosphorylation. Simple catabolic units of fat, carbohydrate and protein are channelled through this cycle so that complete oxidation of the compounds occurs, resulting in carbon dioxide formation; in addition, hydrogen is removed as NADH and reduced flavoproteins. The chief precursor entering the citric acid cycle is acetyl CoA, which is formed from free fatty acids and carbohydrates. Overall, the cycle results in the oxidation of one acetate molecule to two CO2 molecules. Products of the catabolism of amino acids can enter the cycle via α-ketoglutarate, fumarate, succinyl CoA or oxaloacetate. In mammalian tissues, the main limitation of this pathway is the redox state, especially the NADH/NAD+ ratio. NADH inhibits the dehydrogenases of the cycle.
Sulfur mustard analog 2-chloroethyl ethyl sulfide increases triglycerides by activating DGAT1-dependent biogenesis and inhibiting PGC1ɑ-dependent fat catabolism in immortalized human bronchial epithelial cells
Published in Toxicology Mechanisms and Methods, 2023
Feng Ye, Qinya Zeng, Guorong Dan, Yuanpeng Zhao, Wenpei Yu, Jin Cheng, Mingliang Chen, Bin Wang, Jiqing Zhao, Yan Sai, Zhongmin Zou
Fatty acid is a lipolysis product as well as a substrate for energy metabolism. To be transformed to acetyl CoA for the citric acid cycle, fatty acid must be first oxidized. Peroxisome proliferator-activated receptor (PPAR)-γ coactivator 1 (PGC-1) regulates many fatty acid oxidation genes. If the transformation of fatty acid is blocked, lipolysis is also impaired, resulting in TGs accumulation (Haemmerle et al. 2011). PGC-1 family members include PGC1α and PGC1β, which are involved in regulating mitochondrial biosynthesis, mitochondrial oxygen consumption, fatty acid oxidation, adaptive thermogenesis, and hepatic gluconeogenesis. PGC1α and PGC1β are highly homologous (Piccinin et al. 2018), but their expression in specific tissues and after exogenous stimulation may differ (Frier et al. 2009; Ishii et al. 2009).
The ancestral stringent response potentiator, DksA has been adapted throughout Salmonella evolution to orchestrate the expression of metabolic, motility, and virulence pathways
Published in Gut Microbes, 2022
Helit Cohen, Boaz Adani, Emiliano Cohen, Bar Piscon, Shalhevet Azriel, Prerak Desai, Heike Bähre, Michael McClelland, Galia Rahav, Ohad Gal-Mor
Some Enterobacteriaceae species, including S. enterica, are capable of utilizing citrate as a carbon and energy source. Under aerobic conditions, growth on citrate is dependent on an appropriate transport system and a functional tricarboxylic acid (TCA cycle, also known as Krebs or citric acid cycle). Citrate fermentation requires the functional citrate transporter CitT, the citrate lyase (encoded by citCDEFXG), and the two-component regulatory system encoded by citAB.29 RNA-Seq data showed that DksA strongly represses the citrate regulon in S. Typhimurium and also (although to a lesser extent) in S. bongori and E. coli (Figure 3(a)). qRT-PCR analysis confirmed these results and showed that in S. Typhimurium, in the absence of DksA, the expression of citC, citD and citX increased by 6, 2.5, and 3-fold, respectively (Figure 3(b)), indicating that DksA is a negative regulator of the citrate regulon in S. enterica.
Dynamics and metabolic profile of oral keratinocytes (NOK-si) and Candida albicans after interaction in co-culture
Published in Biofouling, 2021
Paula Masetti, Paula Volpato Sanitá, Janaina Habib Jorge
Amino acids are essential for cell metabolism. They act in the production of proteins, are an alternative source of energy, and participate in the synthesis of other metabolites, such as glucose (Kidd and Kerr 1996; Sellick et al. 2015; Sousa et al. 2016; Yang and Vousden 2016). During the analysis of the metabolites, several amino acids were identified, among them alanine, glycine, serine, and threonine. In general, the abundance of the four amino acids identified was higher in the co-culture, in comparison with their abundance in the cells growing alone (Figure 3). One possible explanation is that, with cellular interaction, there may have been a greater production of these amino acids as a defense mechanism, so the production of cellular proteins was enhanced. In addition, data from the metabolism of serine and threonine can be related to the metabolic interactions in the activity of the citric acid cycle. Both amino acids are products of the metabolic reaction from the breakdown of the pyruvate molecule. Additionally, serine and threonine can follow several metabolic fates (dependent on the relative activities of cytosolic and mitochondrial enzymes), including pyruvate (with a potential consequence for alanine production).