Diabetic ketoacidosis
Moshe Hod, Lois G. Jovanovic, Gian Carlo Di Renzo, Alberto de Leiva, Oded Langer in Textbook of Diabetes and Pregnancy, 2018
DKA is a complex metabolic disorder characterized by hyperglycemia, acidosis, and ketonemia.10 It frequently occurs as a consequence of absolute or relative insulin deficiency accompanied by an increased secretion of the counterregulatory hormones (cortisol, glucagon, epinephrine).11 These hormone changes lead to a more marked hepatic gluconeogenesis and glycogenolysis, prompting severe hyperglycemia. Glycogen stores are depleted, and gluconeogenesis is enhanced, partly because of high levels of glucose precursors (and glycerol in particular), as a result of the increased lipolysis and of amino acids from muscle breakdown. Insulin resistance is responsible for the increased lipolysis, which in turn reduces the adipocytes’ capacity to store free fatty acids, which are metabolized as an alternative energy source in the process of ketogenesis.10,12 In particular, the excessive beta-oxidation of fatty acids prompts the formation of large quantities of acetyl CoA, which is then converted by the liver into ketone bodies (3-beta-hydroxy-butyrate and acetoacetate). Acetoacetate undergoes decarboxylation and conversion into acetone. The abundant ketone bodies, and particularly 3-beta-hydroxy-butyrate and lactic acid (which is also used in gluconeogenesis), are the main contributors to the metabolic acidosis.12
Bioenergetics
Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan in Strength and Conditioning in Sports, 2023
Beta-oxidation is a process of extracting energy from FFA. Beta-oxidation is primarily a function of the mitochondrial trifunctional protein. The MTFP is an enzyme complex associated with the inner mitochondrial membrane, although especially long-chain FA are oxidized in oxidative organelles, the peroxisomes. The peroxisomes use a similar oxidative enzyme group as found in the inner mitochondrial membrane. Free fatty acids undergoing β-oxidation result in the accumulation of acetyl-CoA, and H+. The acetyl-CoA can enter the Krebs cycle and the protons, which are carried to the ETS by nicotinic adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD), can enter the electron transport system (ETS) (see Figure 2.5). Type I muscle fibers generally contain high concentrations of oxidative enzymes compared to type II, thus the process of FFA oxidation is quite important for these fibers (35, 79). Fat use during exercise becomes increasingly important with duration (108).
Nutritional Ergogenic Aids: Introduction, Definitions and Regulatory Issues
Ira Wolinsky, Judy A. Driskell in Nutritional Ergogenic Aids, 2004
Aspartate and asparagine are precursors to the Krebs cycle intermediate, oxaloacetate. The amino acid carnitine is the product of lysine and methio-nine (di-peptide) as well as being supplied by the diet. Carnitine is used to transport free fatty acids into the mitochondria for beta-oxidation. In a study where the researchers used a combination of aspartate, asparagines and carnitine and compared it with a control group, those receiving the supplement were able to exercise 40% longer.6 In addition, serum analysis of the blood revealed greater glycogen preservation and free fatty acid utilization by those receiving the dietary supplement. The study has many weaknesses and was not well described in the literature; however, it is feasible that “priming” oxaloacetate production may have an effect on exercise endurance. This study needs modern replication where the combination of amino acids is compared with placebo rather than control. In addition, the replication study should employ a common lactate threshold/time-to-exhaustion trial format.
Ophthalmic manifestations of Heimler syndrome due to PEX6 mutations
Published in Ophthalmic Genetics, 2018
Nutsuchar Wangtiraumnuay, Waleed Abed Alnabi, Mai Tsukikawa, Avrey Thau, Jenina Capasso, Reuven Sharony, Chris F. Inglehearn, Alex V. Levin
The peroxisome is a cytoplasmic organelle. Its main function is the breakdown of very long chain fatty acids through beta-oxidation. The PEX1 and PEX6 proteins bind with adenosine triphosphate (ATP) to form a heterohexameric ATPase which is associated with various cellular activities that fuel essential protein transport across peroxisomal membranes, the final steps of peroxisomal matrix-protein import (19–23). PEX1 and PEX6 are expressed in the retina, especially in photoreceptors (24). Abnormal PEX6 and PEX1 proteins result in abnormal peroxisomal function, leading to the accumulation of very long chain fatty acids. Histopathology of other peroxisomal disorders shows accumulation of characteristic bileaflet fatty acid inclusions in photoreceptors, RPE and pigment laden macrophages (13). Fatty acid accumulation may create the lipofuscin-like substances which appear as hyperfluorescent flecks seen on FAF in our patients.
Radiation metabolomics in the quest of cardiotoxicity biomarkers: the review
Published in International Journal of Radiation Biology, 2020
Michalina Gramatyka, Maria Sokół
The heart, as an organ with very high energy demands, is particularly vulnerable to mitochondrial dysfunction. Mitochondria occupy approximately 40% of the cardiomyocytes volumes, and cardiomyocytes constitute about 75% of the cells in the heart (Barjaktarovic et al. 2011; Sridharan et al. 2014). This allows the heart to produce enough ATP to cover its energy demands. In the heart the processes of beta oxidation of fatty acids provide 60–80% of the produced energy (Constantinou et al. 2007). Glucose, ketone bodies, succinate, lactate, amino acids and proteins also may serve as a fuel for ATP production (Drake et al. 2012; Tapio 2017), although they are less energetically efficient than fatty acids (Ussher et al. 2016). It is reported that cardiac exposure to low doses of radiation shifts the balance of energy production from beta oxidation toward other processes, like glycolysis (Tapio 2017).
De-novo identification of specific exposure biomarkers of the alternative plasticizer di(2-ethylhexyl) terephthalate (DEHTP) after low oral dosage to male volunteers by HPLC-Q-Orbitrap-MS
Published in Biomarkers, 2018
Frederik Lessmann, Daniel Bury, Tobias Weiss, Heiko Hayen, Thomas Brüning, Holger M. Koch
For data processing, we used the Thermo Scientific Compound Discoverer Software Version 2.0.0.303 with the default study design workflow “Metabolism\Find Expected Mark Background”. As a first step, the discovery algorithm of the software utilizes an implemented library of metabolic reactions (divided into phase I and phase II transformations) to calculate exact masses of metabolites originating from a user defined parent structure (in this case DEHTP). The customizable parameter settings for the “Generate Expected Compounds” node for the parent compound di(ethylhexyl) terephthalate (C24H38O4) were as follows: The minimum mass of the dealkylation product was set to 150 Da. A maximum number of dealkylation steps of 2 were allowed, dearylation was not allowed. All phase I and phase II transformations from the default transformation library were allowed. In addition, we added the phase I transformation step “beta-oxidation” with “C2H4” as a leaving group, to account for β-oxidized metabolites (i.e. carboxylic acid metabolites with an alkyl chain shortened by one C2H4 unit). The maximum number of all transformation steps (counting any number of dealkylation steps as one step) was set to six, with a maximum of one phase II transformation. [M-H]− was set as the only ionic species to be screened for.
Related Knowledge Centers
- Biochemistry
- Fatty Acid
- Flavin Adenine Dinucleotide
- Nicotinamide Adenine Dinucleotide
- Metabolism
- Catabolism
- Citric Acid Cycle
- Cytosol
- Mitochondrion
- Acetyl-Coa