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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.
Muscle Disorders
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Kourosh Rezania, Peter Pytel, Betty Soliven
Autosomal recessive disorder caused by impaired transport of free fatty acids into mitochondria. The abnormal gene maps to chromosome 1. Carnitine palmitoyltransferase II (CPT2) deficiency is the most common inherited cause of recurrent myoglobinuria.
Carnitine-acylcarnitine translocase deficiency
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
Mitochondrial oxidation of long-chain fatty acids provides an important source of energy for the heart, as well as for skeletal muscle during prolonged aerobic work and for hepatic ketogenesis during long-term fasting. The carnitine shuttle is responsible for transferring long-chain fatty acids across the barrier of the inner mitochondrial membrane to gain access to the enzymes of β-oxidation. The shuttle consists of three enzymes (carnitine palmitoyltransferase [CPT] 1, carnitine-acylcarnitine translocase [CACT], CPT 2) and a small, soluble molecule (carnitine) to transport fatty acids as their long-chain fatty acylcarnitine esters. Carnitine is provided in the diet (animal protein) and also synthesized at low rates from trimethyllysine residues generated during protein catabolism. Carnitine turnover rates (300–500 μmol/day) represent <1 percent of body stores; 98 percent of carnitine stores are intracellular (total carnitine levels are 40–50 μM in plasma versus 2–3 mM in tissue). Carnitine is removed by urinary excretion after reabsorption of 98 percent of the filtered load; the renal carnitine threshold determines plasma concentrations and total body carnitine stores [5].
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).
Logistic role of carnitine shuttle system on radiation-induced L-carnitine and acylcarnitines alteration
Published in International Journal of Radiation Biology, 2022
L-carnitine (β-hydroxy-γ-trimethylammonium butyrate) as a carrier of the carnitine shuttle system which is comprised of the carnitine palmitoyltransferase 1 (CPT1) and 2 (CPT2), the carnitine-acylcarnitine translocase (CACT), and the carnitine acetyltransferase (CrAT) to transport long-chain fatty acids from the cytosol into mitochondria (Ramsay et al. 2001; Virmani et al. 2015; Houten et al. 2016). The carnitine shuttle system controls the flux of fatty acid β-oxidation (FAO). Long-chain (C14–C20) fatty acid acyl groups are transported exclusively as carnitine esters by the carnitine shuttle system. In contrast, the short- (C2–C5) and medium-chain fatty acids are transported into the mitochondrial matrix without any carnitine assistance in the process. In addition, most of the acylcarnitines, which are esters of L-carnitine and acyl groups, are derived from the intermediates of FAO. The alteration of the carnitine pool comprised free L-carnitine and various acylcarnitines in blood and urine might represent the changing flux of FAO.
The second phase of brain trauma can be controlled by nutraceuticals that suppress DAMP-mediated microglial activation
Published in Expert Review of Neurotherapeutics, 2021
As noted above, type 1 HDAC activity is required for efficient activation of NF-kappaB in LPS-stimulated microglia. Consistent with this, valproic acid and other pharmaceutical inhibitors of such activity have been shown to blunt inflammatory microglia activation, decrease lesion volume, and improve functional recovery in rodent models of brain trauma and stroke [121–127,142–147]. Curiously, the ketone body beta-hydroxybutyrate (BHB) can act as a type 1 HDAC inhibitor, in low millimolar concentrations that be achieved in plasma during fasting [127,147]. This may explain why ketogenic diets or 24-h fasting have been found to be protective in rodent brain trauma models [128–130,148–150]. Joint administration of carnitine and the phytochemical nutraceutical hydroxycitrate may accelerate onset of brisk ketosis during fasting or ketogenic dieting by optimizing hepatic activity of carnitine palmitoyl transferase [131,151].