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Lipids and Lipid Metabolism in Postnatal Gut Development and Risk of Intestinal Injury
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
Utilization of fatty acids at the cellular level begins with internalization of the fatty acid into the cell via fatty acid transporters. Once within the cell, the fatty acid is converted to fatty acyl-CoA via fatty acyl-CoA synthase (Figure 49.2). At the outer membrane of the mitochondria, carnitine palmitoyltransferase 1 converts the fatty acid-CoA to fatty acyl carnitine. Fatty acyl carnitine then crosses the inner mitochondrial membrane through a carnitine exchange via carnitine-acyl carnitine translocase. Once inside the mitochondrial matrix, the fatty acyl carnitine is converted back to fatty acyl-CoA via carnitine palmitoyltransferase 2, allowing for entry into the β-oxidation pathway generating acetyl-CoA. Acetyl-CoA is utilized by the tricarboxylic acid cycle (TCA) cycle to form NADH and FADH2.
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.
Diseases of the Nervous System
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
The brain has an absolute dependence on the oxidation of carbohydrates. Lack of glucose by any means will depress cerebral metabolism and consequently affecting function. Insulininduced hypoglycemia can also reduce brain metabolism. The effect is reversible if the hypoglycemia is of short duration and not excessive. There are differences in the events occurring during ischemia and hypoglycemia. During hypoglycemia, metabolic changes are different from those in circulatory failure, and the onset of functional and metabolic changes is slow. The tricarboxylic acid cycle is functioning and the concentration of endogenous substrates is enough to maintain energy metabolism for 20 to 25 min. Hypoglycemia may occur in the brain associated with liver disease, insulin-secreting tumors, and insulin overdose. The clinical signs of hypoglycemia, such as increased perspiration and tachycardia, are due to the release of large amounts of epinephrine. Drowsiness and confusion are apparent when blood glucose is reduced to 30 mg/dl, and coma ensues at 20 mg/dl. Below this level there is loss of neurons. Prolonged hypoglycemia can produce permanent damage, mental and psychological disorders, and death. Infantile hypoglycemia is found to be a significant cause of neonatal brain damage.
Recent progress in the development of nanomaterials targeting multiple cancer metabolic pathways: a review of mechanistic approaches for cancer treatment
Published in Drug Delivery, 2023
Ling Zhang, Bing-Zhong Zhai, Yue-Jin Wu, Yin Wang
Despite the low blood pressure within the tumors, lymphatic insufficiency and blood vessel leaks play a role in making blood serum or its albumin protein accessible to cancer cells. Macropinocytosis occurs more frequently in Ras-driven tumors, which makes it easier for them to internalize extracellular proteins (ECPs) (Finicle et al., 2018). Additionally, it has been noted that inhibition of the mTORC1 signaling pathway causes cancer cells to become dependent on extracellular macromolecules rather than amino acids in the event of nutrient deprivation. In an experiment, AMPK activation and mTORC1 suppression in a state of glucose and amino acid starvation facilitate tumor proliferation by scavenging cell debris in Phosphatase and Tensin Homolog (PTEN) deficient prostate cancer cell lines and K-Ras-driven pancreatic tumors (Kim et al., 2018). Amino acids from cell debris participate in the building of cell biomass. Furthermore, when starved of glucose and glutamine, pancreatic ductal adenocarcinoma (PDAC) can internalize collagen I and IV. To produce proline, PDAC cells break down the internalized collagen in the lysosomes (Olivares et al., 2017). Extracellular signal-regulated kinase pathways that result in the production of ATP and, ultimately, cell survival feed proline into the tricarboxylic acid cycle. In vitro studies reveal that cancer cells utilize albumin as an alternative source of nutrients (Recouvreux and Commisso, 2017). An in vivo study shows that PDAC cells can take in albumin and use the amino acids it contains in other metabolic pathways, which normal cells can’t do (Lambies and Commisso, 2022).
Exploratory metabolomic analysis based on UHPLC-Q-TOF-MS/MS to study hypoxia-reoxygenation energy metabolic alterations in HK-2 cells
Published in Renal Failure, 2023
Xiaoyu Yang, Ailing Kang, Yuanyue Lu, Yafeng Li, Lili Guo, Rongshan Li, Xiaoshuang Zhou
Succinic acid and malate (Figure 8(C,D)) are involved in energy metabolism as TCA circulating metabolites. Under conditions of ischemia and hypoxia, malate is dehydrated to fumarate, which is reduced to succinate, accumulates to drive reactive oxygen species generation and compensates for the reduced pool of electron donors and carriers, and after reperfusion, succinate accumulated during ischemia is rapidly oxidized [42,43]. Acetyl coenzyme A (Figure 8(E)) acts as a substrate for the tricarboxylic acid cycle, releasing large amounts of energy. In addition, the glutamine enters the TCA cycle, and glutamine (Figure 8(F)) enters the mitochondria to form glutamate, which, as mentioned above, is converted to α-ketoglutarate to replenish the TCA cycle [12,44,45]. This suggests that the kidney produces ATP by altering metabolic substrates to maintain the energy deficit at the time of injury.
Association of hyperuricemia with cardiovascular diseases: current evidence
Published in Hospital Practice, 2023
1. Uric acid-induced oxidative stress: Uric acid has been shown to have both antioxidant and prooxidant properties with the latter being more dominant. With respect to its antioxidant effects, it reacts with hydroxyl radicals, peroxynitrite, NO, and scavenges the production of ROS. Regarding its prooxidant effects, these are mediated through a decrease in production of NO in vascular endothelial cells with reduction of vasodilation. In addition, it interferes with the tricarboxylic acid cycle and decreases the fatty acid β oxidation. It also increases the production of angiotensin II (Ang II), stimulates the proliferation of vascular smooth muscle cells, and generates chronic inflammation through stimulation of the inflammasome and increases the oxidation of LDL-C leading to atherosclerosis and atheromatous plaque formation [59]. The antioxidant effects of UA occur usually in the plasma, whereas its prooxidant effects occur within the cells and are responsible for its adverse CV effects [60].