General concepts for applied exercise physiology
Nick Draper, Helen Marshall in Exercise Physiology, 2014
Enzymes are classified in a number of ways and these reveal much about the function of the enzyme. Generally the first part of the name of an enzyme refers to the substrate with which it is associated, for instance creatine kinase catalyses the reversible reaction to form phos-phocreatine from creatine and Pi. The second part of an enzyme name relates to the type of reaction it catalyses while the ‘ase’ indicates that the protein-based structure is an enzyme. Kinases, as with the term kinetics, are associated with work, for example the transfer of a phosphoryl group to or from a substrate. Isomerases and mutases, however, change the structure of the substrate, for example glucose phosphate isomerase, (discussed in the section on glycolysis in Chapter 10) changes the structure of the substrate in its reaction but does not alter the chemical composition. Another important enzyme category, within the cellular metabolic pathways, are the dehydrogenases which catalyse a specialised group of oxidation and reduction (redox) reactions (the loss or gaining of electrons). Dehydrogenases, such as lactate dehydrogenase, catalyse reactions that lead to the removal or addition of hydrogen atoms from or to a substrate.
Thiamin
Judy A. Driskell, Ira Wolinsky in Sports Nutrition, 2005
Thiamin pyrophosphate is also the cofactor for the pyruvate dehydrogenase component of the complex. Pyruvate dehydrogenase catalyzes the oxidative decarboxylation of pyruvate. Other components of the enzyme complex complete the conversion of pyruvate to acetyl CoA. Other reactions that require TPP involve α–ketoglutarate and branched-chain α-keto acids. This reaction has a similar metabolic pathway to that of pyruvate.37 Alpha-ketoglutarate is decarboxylated and the product is transferred to CoA to give succinyl CoA by action of TPP dependent α-ketoglutarate dehydrogenase. Also, in BCAA catabolism, TPP is required as a coenzyme for branched-chain keto-acid dehydrogenase for the oxidative decarboxylation of α-ketoglutarate and branched chains derived from certain amino acids (valine, luecine, isoluecine).38
Branched chain keto acid dehydrogenase kinase (BCKDK) deficiency
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Deficiency of BCKDK has been reported in six patients with very severe deficiency of motor and cognitive function, autism, seizures and cerebral atrophy [1, 2]. The kinase enzyme is responsible for phosphorylating the enzyme branched chain keto acid dehydrogenase (Figure 20.1). This phosphorylation downregulates the activity of the enzyme; so, its deficiency leads to very robust dehydrogenase activity. This increased oxidation of the branched chain amino acids leads to very low concentrations of the branched chain amino acid leucine isoleucine and valine, in the blood and CSF fluid. Plasma concentrations reported have been under 20 μmol/L. The activity of the enzyme has been found to be defective. Mutations reported have included p.R174Gfs and on the other allele p.L389P [2] and homozygosity for pM74fs, p.R156X and p.R224P [1]. Some improvement has been reported after treatment designed to increase levels of the branched chain amino acids, and neurologic abnormalities were abolished in an animal model within a week of starting a diet enriched with branched chain amino acids.
Anti-biofilm effect of a butenolide/polymer coating and metatranscriptomic analyses
Published in Biofouling, 2018
Wei Ding, Chunfeng Ma, Weipeng Zhang, Hoyin Chiang, Chunkit Tam, Ying Xu, Guangzhao Zhang, Pei-Yuan Qian
Firstly, comparing the DCOIT-treated biofilms and the control biofilms, genes involved in energy production, including enoyl-coenzyme A hydratase/carnithine racemase (COG1024) and acyl-coenzyme A dehydrogenases (COG1960) had lower abundance in the butenolide treated biofilms, suggesting inhibition of these genes by butenolide. In particular, acyl-coenzyme A dehydrogenase is an enzyme which generates energy by catalyzing the β-oxidation of long chain fatty acids (McAndrew et al. 2008). It has been demonstrated that butenolide binds to very long chain acyl-coenzyme A dehydrogenase, actin, and glutathione S-transferases in the barnacle Balanus (=Amphibalanus) amphitrite, and based on the result of in vitro molecular assay using purified proteins and compounds, butenolide binds to the succinyl-coenzyme A synthetase β subunit in the marine bacterium Vibrio sp. UST020129-010 to inhibit its growth (Zhang et al. 2012). These results imply that butenolide inhibits marine biofilm formation by altering the primary metabolism in microbes. It is worthwhile mentioning that some biocides also affect energy metabolism in bacteria. For example, tetrakis (hydroxymethyl) phosphonium sulfate has been shown to affect energy metabolic pathways in sulfate-reducing bacteria (Lee et al. 2010).
Improving mitochondrial function in preclinical models of heart failure: therapeutic targets for future clinical therapies?
Published in Expert Opinion on Therapeutic Targets, 2023
Anna Gorący, Jakub Rosik, Joanna Szostak, Bartosz Szostak, Szymon Retfiński, Filip Machaj, Andrzej Pawlik
Mitochondrial dysfunction also leads to increased lipid peroxidation, resulting in the production of highly reactive carbonyls, such as various ketones, alkanes, and aldehydes. A key role in these processes is played by aldehyde dehydrogenase (ALDH2). ALDH2 is involved in the removal and metabolism of exogenous chemicals and endogenous reactive aldehydes to maintain homeostasis and normal mitochondrial function [200]. This enzyme appears to be a promising target for therapy aimed at improving mitochondrial function in patients with HF. In an animal model of HF induced by myocardial infarction, ALDH2 activation was shown to reduce the concentration of reactive aldehydes in cardiomyocytes and limited. Most therapies to date affecting mitochondrial metabolism have focused on single factors or processes disrupted in HF. However, in this disease, there are multidirectional disorders improve mitochondrial bioenergetics [201]. Moreover, sustained ALDH2 activation prevented myocardial hypertrophy, fibrosis, and cardiac dysfunction.
Exposure of human intestinal epithelial cells and primary human hepatocytes to trypsin-like serine protease inhibitors with potential antiviral effect
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Erzsébet Pászti-Gere, Judit Pomothy, Ákos Jerzsele, Oliver Pilgram, Torsten Steinmetzer
The assay is based on the ability of living cells to reduce the MTS tetrazolium compound to a coloured formazan product soluble in the cell culture medium. The reduction is carried out by an NAD(P)H-dependent dehydrogenase in metabolically active cells. The HIEC-6 and the hepatocytes were placed onto 96-well-plates and incubated for 24 h with the inhibitors at 5, 20, 50, and 100 µM concentrations. The MTS assay was performed with eight parallels at each inhibitor concentration. After removing the medium and three times washing of the cells with PBS, 20 µL of CellTiter96 Aqueous One Solution (Promega Corporation, Madison, WI) containing MTS and an electron acceptor reagent, phenazine ethosulfate, were pipetted into a 96-well plate, each containing 100 µL of phenol red free medium. The plate was incubated for 1.5 h in a 5% CO2 incubator. The viability of HIEC-6 was detected with an EZ Read Biochrom 400 microplate reader (Biochrom, Cambridge, UK) at 490 nm.
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