Metabolism
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
The combustion of fatty acids, the major energy component of fats, commences with their activation to CoA derivatives such as palmitoyl CoA. Palmitoyl CoA must be first converted to palmitoylcarnitine by carnitine-palmitoyltransferase in the outer mitochondrial membrane before it can enter the mitochondrion. At the inner mitochondrial membrane, palmitoyl carnitine is reconverted to palmitoyl CoA and then oxidized by β-oxidation, which releases two carbon compounds as acetyl CoA until the entire fatty acid molecule is broken down. β-Oxidation of free fatty acids provides a major source of acetyl CoA, an important substrate for the citric acid cycle. Free fatty acids in blood, derived from the diet or by the action of lipoprotein lipase on lipoproteins at the endothelial cell layer of tissue, are oxidized in the mitochondria. Growth hormone and glucocorticoid increase the mobilization of fat stores by increasing the amount of triglyceride lipase. Initially, free fatty acid is converted to acyl CoA utilizing one ATP. Acyl CoA is oxidized to acetyl CoA, and the residual carbon atoms re-enter the cycle to produce more acetyl CoA (Figure 65.6). This partial oxidation of free fatty acids produces hydrogen ions that are removed as NADH and reduced flavoproteins.
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 combustion of fatty acids, the major energy component of fats, commences with their activation to CoA derivatives such as palmitoyl CoA. Palmitoyl CoA must be first converted to palmitoyl-carnitine by carnitine-palmitoyl transferase in the outer mitochondrial membrane before it can enter the mitochondria. At the inner mitochondrial membrane, palmitoylcarnitine is reconverted to palmitoyl CoA and then oxidized by β-oxidation, which releases two carbon compounds as acetyl CoA until the entire fatty acid molecule is broken down. β-Oxidation of free fatty acids provides a major source of acetyl CoA, an important substrate for the citric acid cycle. Free fatty acids in blood, derived from the diet or by the action of lipoprotein lipase on lipoproteins at the endothelial cell layer of tissue, are oxidized in the mitochondria. Growth hormone and glucocorticoid increase the mobilization of fat stores by increasing the amount of triglyceride lipase. Initially, free fatty acid is converted to acyl CoA utilizing one ATP. Acyl CoA is oxidized to acetyl CoA, and the residual carbon atoms reenter the cycle to produce more acetyl CoA (Figure 12.6). This partial oxidation of free fatty acids produces hydrogen ions that are removed as NADH and reduced flavoproteins.
Carnitine palmitoyl transferase II deficiency, lethal neonatal
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Long-chain fatty acids require a carnitine transport system in order to gain entrance to the mitochondrial matrix where β-oxidation takes place. CPT II is located on the inner side of the inner mitochondrial membrane. It catalyzes the conversion of long-chain acylcarnitine esters, like palmitoylcarnitine, to free carnitine and the corresponding CoA ester, such as palmitoyl CoA.
Logistic role of carnitine shuttle system on radiation-induced L-carnitine and acylcarnitines alteration
Published in International Journal of Radiation Biology, 2022
Hai-Xiang Liu, Qing-Jie Liu
Acylcarnitines represent a ‘dormant’ pool of acyl groups that may be used in biochemical pathways upon their conversion back into acyl-CoA esters by carnitine acyltransferases (Adeva Andany et al. 2017). Acyl groups pool provides activated substrates for many critical metabolic pathways such as tricarboxylic acid cycle (TCA), lipid, and cholesterol synthesis for proteins posttranslational modification and detoxication mechanisms (Niu et al. 2019). In this context, acetylcarnitine (C2) donates acetyl group for histone acetylation to modulate epigenetic properties. Acetyl-L-carnitine can be converted into malonyl-CoA in the cytosol to inhibit the activity of CPT1 and reduce the oxidation of fatty acids, which results in eliminating the adverse reactions caused by the accumulation of acyl-CoA metabolic intermediates in the mitochondria (Casals et al. 2016). The long-chain acylcarnitines, notably palmitoylcarnitine, are related to palmitoylation levels of specific proteins (Chen et al. 2017; Niu et al. 2019; Yao et al. 2019). Palmitoylation of proteins is a pervasive posttranslational modification that regulates the transport, compartmentalization and stability of protein, involved in many biological processes such as apoptosis and proliferation.
Liver metabolomic characterization of Sophora flavescens alcohol extract-induced hepatotoxicity in rats through UPLC/LTQ-Orbitrap mass spectrometry
Published in Xenobiotica, 2020
Peng Jiang, Yancai Sun, Nengneng Cheng
The liver metabolomic results of the rats after they were orally exposed to SFAE showed a disturbance of fatty acid metabolism. Increased acetylcarnitine, l-carnitine, stearoylcarnitine and palmitoylcarnitine levels and decreased 3-hydroxybutyric acid levels indicated the inhibition of ketone body generation, which is the primary cause of steatosis. Betaine also plays a role in the manufacture of carnitine and protects kidneys from damage. Betaine insufficiency is associated with lipid disorders, metabolic syndrome and diabetes (Pekkinen et al., 2013). Betaine is also widely regarded as an anti-oxidant and used to treat liver disorders. Palmitoylcarnitine significantly increases from normal levels in steatosis samples. Alterations in carnitine levels are a result of abnormal lipid metabolism and high lipid loads (Schooneman et al., 2013).
Screening of radiation gastrointestinal injury biomarkers in rat plasma by high-coverage targeted lipidomics
Published in Biomarkers, 2022
Cong Xi, Hua Zhao, Hai-Xiang Liu, Jia-Qi Xiang, Xue Lu, Tian-Jing Cai, Shuang Li, Ling Gao, Xue-Lei Tian, Ke-Hui Liu, Mei Tian, Qing-Jie Liu
Interestingly, 15 differential fatty acids in the jejunum were all decreased while 20 out of 23 differential fatty acids in plasma increased after irradiation, suggesting the elevated fatty acids in plasma may partly originate from the jejunum. FA (16:0) (palmitic acid) and FA (18:0) (stearic acid) are the most common long-chain fatty acids in organisms. In this study, levels of FA (16:0) and FA (18:0) significantly decreased with a good dose-response relationship in the jejunum while significantly increasing in plasma. Previous radiation metabolomics study revealed that at the same time point (72 h post-irradiation), palmitoylcarnitine significantly increased with a good dose-response relationship in rat plasma (Zhao et al.2020). It has been reported that the accumulation of long-chain acylcarnitine can cause hypoxia to important tissues with high oxygen consumption, whose energy demand mainly comes from fatty acid oxidation (Ahmad et al.2016). In the process of β-oxidation of fatty acids in mitochondria, long-chain fatty acids, such as FA (16:0) and FA (18:0) must be formulated as acylcarnitine to pass through the mitochondrial membrane (Eaton et al.1996). The imbalance of acylcarnitine and the disturbance of fatty acid oxidation metabolism can lead to impaired mitochondrial function, resulting in radiation-induced tissue injury (Prithivirajsingh et al.2004). Changes in fatty acids in the current study may indicate radiation-induced mitochondrial energetics disorders. It is worthwhile to systematically investigate fatty acids and fatty acylcarnitine profiles in the jejunum and circulation as well as upstream molecules in the metabolic pathway in future studies to test this hypothesis.
Related Knowledge Centers
- Ester
- Fatty Acid
- Carnitine
- Carnitine O-Palmitoyltransferase
- Carnitine-Acylcarnitine Translocase