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Introduction to disorders of fatty acid oxidation
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
A summation of the various pathways involved in fatty acid oxidation and their interrelations is shown in Figure 34.1. Abnormality in those pathways has often first been suggested chemically by the excretion of dicarboxylic acids in the urine. Dicarboxylic aciduria may also be dietary, especially in infants receiving formulas containing medium-chain triglycerides. When ß-oxidation is defective, ω-oxidation and hydroxylation take place in the microsomal P450 system. This takes place efficiently in the case of long-chain fatty acyl CoA compounds, but the affinity of the system for medium-chain chain compounds is so low that they are thought to result from ß-oxidation in peroxisomes of longer chain dicarboxylic or hydroxy acids [4].
Myocardial Metabolism During Diabetes Mellitus
Published in Grant N. Pierce, Robert E. Beamish, Naranjan S. Dhalla, Heart Dysfunction in Diabetes, 2019
Grant N. Pierce, Robert E. Beamish, Naranjan S. Dhalla
The defect in energy metabolism in the heart during diabetes has also been suggested to involve carnitine. Carnitine and associated cofactors are essential constituents in fatty acid oxidation. Without carnitine, metabolism of fatty moieties would be significantly impaired. Its central role in fatty acid metabolism is depicted in Figure 9. The fatty acyl group combines with coenzyme A in the cytoplasm of the cell to form acyl-CoA. Acyl-CoA can pass through the freely permeable outer mitochondrial membrane but it cannot move through the more selective permeability barrier offered by the inner mitochondrial membrane. The function of carnitine is to transport the acyl-CoA group across the inner mitochondrial membrane. Carnitine acyl-transferase, an enzyme bound to both sides of the inner mitochondrial membrane, catalyzes the formation of acyl-carnitine and coenzyme A from free carnitine and acyl-CoA. The acyl-carnitine can pass through the inner mitochondrial membrane in exchange for free carnitine through the action of the membrane-bound carnitine/acyl-carnitine translocase protein.98 The carnitine acyl-transferase enzyme which is bound to the inner surface of the inner mitochondrial membrane then catalyzes the reformation of free carnitine and acyl-CoA from the transported acyl-carnitine and coenzyme A. The acyl-CoA which is now located within the cristae is available for β-oxidation and subsequent metabolism and energy production.
Alterations in Myocardial Energy Metabolism in Streptozotocin Diabetes
Published in John H. McNeill, Experimental Models of Diabetes, 2018
William C. Stanley, Gary D. Lopaschuk, Krista M. Kivilo
In addition to regulation of flux through PDH by phosphorylation of the enzyme, it is important to note that the rate of flux for any given phosphorylation state is largely a function of both the concentration of the products and substrates of PDH. Acetyl CoA produced from fatty acid oxidation in the mitochondrial matrix causes direct product inhibition of flux through PDH.39 Thus, elevated rates of fatty acid and/or ketone body oxidation not only inhibit flux through PDH by elevating the concentrations of NADH and acetyl CoA, and stimulating PDH kinase and phosphorylating PDH, but also by inhibiting flux through PDH for any given PDH phosphorylation state. Flux through PDH is also dependent on the pyruvate concentration, which could be decreased in the diabetic heart because of a lower rate of glycolysis. However, it has not yet been unequivocally established that a decrease in pyruvate supply to PDH contributes to the low pyruvate oxidation in STZ diabetes.
Protective effect of Qingluotongbi formula against Tripterygium wilfordii induced liver injury in mice by improving fatty acid β-oxidation and mitochondrial biosynthesis
Published in Pharmaceutical Biology, 2023
Jie Zhou, Ming Li, Zhichao Yu, Changqing Li, Lingling Zhou, Xueping Zhou
Mitochondria are the key organelles involved in cellular lipid metabolism and have been reported to be the targets for various drug-induced hepatotoxicities (Begriche et al. 2011). Studies have shown that mitochondrial damage is one of the main mechanisms of triptolide cytotoxicity, the main active and toxic component of TW (Yao et al. 2008; Fu et al. 2013; Chen et al. 2020). Liver lipid homeostasis can be disrupted by mitochondrial dysfunction, such as inhibited fatty acid oxidation (Natarajan et al. 2006; Chen et al. 2007). The fatty acid oxidation process produces acetyl-CoA, which will be oxidized in the tricarboxylic acid cycle, and provides electrons passed to the respiratory chain for ATP synthesis, ensuring cellular energy supply. There is evidence that mitochondrial fatty acid oxidation and oxidative phosphorylation processes are not only functionally interrelated but also physically connected, which can reduce electron leakage and ROS production during the processes (Wang et al. 2019).
Low-intensity exercise diverts cardiac fatty acid metabolism from triacylglycerol synthesis to beta oxidation in fructose-fed rats
Published in Archives of Physiology and Biochemistry, 2023
Milan Kostić, Goran Korićanac, Snežana Tepavčević, Jelena Stanišić, Snježana Romić, Tijana Ćulafić, Tamara Ivković, Mojca Stojiljković
Inside the cardiomyocyte FA are converted into fatty acyl-CoA esters and can then proceed down either of three major pathways: they can undergo β-oxidation and ATP production; they can be esterified into TAG, diacylglycerols (DAG) or phospholipids; or converted to sphingolipids (Brindley et al.2010, Chavez and Summers 2010). Fatty acid oxidation in the mitochondria is essential for energy homeostasis in the absence of a consistent energy supply, especially during prolonged fasting or exercise (Goodwin and Taegtmeyer 2000, Smith et al.2018). The carnitine palmitoyltransferase (CPT) system, made up of two distinct proteins corresponding to the outer and inner membrane forms, CPT1 and CPT2, respectively, acts to transport long-chain FA across the mitochondrial membranes (Kodde et al.2007). CPT1 is the key rate-limiting enzyme of mitochondrial FA uptake (Zhang et al.2010).
New insights into the metabolism of Th17 cells
Published in Immunological Medicine, 2023
Fatty acid oxidation is a mitochondrial aerobic process responsible for producing acetyl CoA from fatty acids. In contrast, fatty acid synthesis is the creation of fatty acids from acetyl CoA and Nicotinamide adenine dinucleotide phosphate (NADPH) [13]. Adenosine monophosphate-activated protein kinase (AMPK), a serine/threonine kinase, is a vital metabolic regulator that inhibits mTORC activity. AMPK-dependent phosphorylation of acetyl-CoA carboxylase 1 (ACC1) is the rate-limiting enzyme for fatty acid synthesis. ACC1 modulates the DNA binding of RORγt to target genes and enhances Th17 cell differentiation [79–81]. Cholesterol is synthesized from acetyl CoA by the hydroxymethylglutaryl-coenzyme A (HMG-CoA). Statin, an inhibitor of HMG-CoA reductase, reduces Th17 cell differentiation [82].