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Influence of medication on typical exercise response
Published in R. C. Richard Davison, Paul M. Smith, James Hopker, Michael J. Price, Florentina Hettinga, Garry Tew, Lindsay Bottoms, Sport and Exercise Physiology Testing Guidelines: Volume II – Exercise and Clinical Testing, 2022
Phase II reactions – Phase II reactions involve conjugation by coupling a drug or its metabolites to another molecule, such as glucuronidation, acylation, sulfate or glycine. These metabolic pathways are dependent on the availability of a number of cofactors. Chief amongst these cofactors is acetyl coenzyme A (CoA). The effects of exercise on CoA are innumerate, but it is worth considering that they may have implications for any medications prescribed (Sarmiento et al., 2016). This is especially the case in people new to physical activity.
Micronutrients
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
Cofactors are inorganic molecules such as metal ions or nonprotein compounds that are bound to an enzyme for its functioning. Cofactors tightly bound to the protein form metalloenzymes, while those that are loosely associated with the protein are termed activator ions (90–92). Metalloenzymes are enzyme proteins containing metal cofactors, which are covalently bound to the enzyme. About one-third of all enzymes are metalloenzymes. For example: iron in cytochrome oxidase, copper in catalase, zinc in alcohol dehydrogenase, alkaline phosphatase, and so on (91–93). In humans, the metalloid selenium forms the active site of several antioxidant enzymes including glutathione peroxidase, thioredoxin reductase, iodothyronine deiodinase, formate dehydrogenase, and glycine reductase. Some cofactors are essential at the active site of a reaction, while others help maintain the structural integrity of an enzyme or protein (90). Therefore, when these mineral activators are absent in foods, enzymes become inactive and diseases appear.
Vitamin C in Pneumonia and Sepsis
Published in Qi Chen, Margreet C.M. Vissers, Vitamin C, 2020
Vitamin C is a potent water-soluble antioxidant, able to scavenge a wide range of reactive oxygen species, thus protecting essential cellular structures, metabolic functions, and signaling pathways from oxidative damage [105,106]. Vitamin C also exhibits anti-inflammatory activity with inverse associations observed between vitamin C and pro-inflammatory cytokines and acute phase reactants such as C-reactive protein and procalcitonin [39,45,56,57,77]. Severe infection and sepsis are characterized by significant oxidative stress and overwhelming inflammatory mediators, sometimes referred to as a “cytokine storm” [107,108]. These stressors can contribute to the pathophysiology of sepsis, such as impaired microcirculatory flow, coagulopathy, capillary plugging, increased endothelial dysfunction and permeability, and multiorgan failure [109,110]. As such, the role of vitamin C in severe infection and sepsis has often focused on its antioxidant and anti-inflammatory functions and effects on signaling pathways [109,110]. However, less attention has been paid to its role as an enzyme cofactor.
Characterisation of seven medications approved for attention-deficit/hyperactivity disorder using in vitro models of hepatic metabolism
Published in Xenobiotica, 2022
Rebecca Law, David Lewis, Daniel Hain, Rachel Daut, Melissa P. DelBello, Jean A. Frazier, Jeffrey H. Newcorn, Erika Nurmi, Elizabeth S. Cogan, Susanne Wagner, Holly Johnson, Jerry Lanchbury
CLD loss was 6.4% on average over the 2-h incubation period (Table 2). This corresponds with the finding in cPHHs. Notably, 4-OH-CLD formed in low amounts, and was inhibited 74.6% by paroxetine and 31.4% by phencyclidine (Table 3). Given that phencyclidine, along with being a strong CYP2B6 inhibitor, is a moderate inhibitor of CYP2D6, it is likely that only CYP2D6 plays a role in 4-OH-CLD formation and the inhibition by phencyclidine is due to a lack of enzyme specificity. The remaining conditions did not meaningfully impact 4-OH-CLD formation. Also, the formation of 2-[(2,6-dichlorophenyl)-imino]-imidazolidine-4-one was only observed in cPHHs and not in HLMs. It is possible that the enzyme responsible for its formation is not retained in HLMs or it requires a cofactor other than NADPH and UDPGA.
Frontiers of metal-coordinating drug design
Published in Expert Opinion on Drug Discovery, 2021
Giulia Palermo, Angelo Spinello, Aakash Saha, Alessandra Magistrato
Due to their optimal redox potential, reactions mediated by copper enzymes promote fundamental biological processes (i.e. cellular respiration, iron oxidation, antioxidant defense) [9]. Yet, an excessive concentration of copper can possibly trigger cytotoxic cellular damages, as implicated in neurodegenerative disorders and cancer [10]. Deregulated copper metabolism, due to genetic abnormalities in Cu transporters, is responsible for Menkes’ and Wilson’s diseases [11]. In this respect, ligands that regulate misfunction of Cu(I) metabolism offer appealing opportunities to counteract these pathological states [12]. Zinc ions are the natural cofactors of a wide variety of enzymes such as (i) matrix metalloproteinase (MMP), responsible for protein degradation at the cell-extracellular matrix, typically targeted by anticancer compounds [13]; (ii) human carbonic anhydrase (hCA), promoting reversible hydration of carbon dioxide to bicarbonate [14], whose inhibitors exhibit several medical applications (i.e. diuretics, anticonvulsants, as anticancer agents/diagnostic tools for tumors, antiobesity agents); (iii) bacterial metallo-β-lactamases (MBL) enzymes that promote the degradation of β-lactam antibiotics. Their inhibitors are of critical importance to counteract resistance to commonly used β-lactam antibiotics [15,16].
The aging brain: impact of heavy metal neurotoxicity
Published in Critical Reviews in Toxicology, 2020
Omamuyovwi M. Ijomone, Chibuzor W. Ifenatuoha, Oritoke M. Aluko, Olayemi K. Ijomone, Michael Aschner
The process of aging is accompanied by several morphological and functional alterations in the nervous system as it also affects other organ systems. Based on cellular and molecular evidence, neurons and glia in the brain are susceptible to oxidative stress, mitochondrial dysfunctions, aggregation of damaged proteins, ion dyshomeostasis, diminished clearance of toxins, metabolic impairment, DNA damage, and apoptosis, as a result of aging. These changes culminate into neuronal death and are aggravated in some selected vulnerable neurons (Mattson and Magnus 2006). Several essential metals have been considered to possess neurotoxic ability during aging. These metals include calcium, cobalt, copper, iron, magnesium, manganese, molybdenum, selenium, sodium, and zinc. These metals play vital roles in many biological processes in the body. For example, they serve as cofactors for enzymes. However, a change in the concentration of these metals above or below the optimum level is considered harmful. Conversely, non-essential metals, such as nickel, cadmium, lead, mercury, tin, and aluminum, possess no biological functions (Caito and Aschner 2015). The dysregulation of these metals in the aging brain causes several alterations and increases the risk of age-related neurodegenerative diseases. However, before discussing the neurotoxic impact of metals in the aging brain, it is pertinent to elucidate those associated metabolic and cellular alterations that occur during brain aging, which, have been collectively called the hallmarks of aging in the brain (Mattson and Magnus 2006), as summarized in Table 1.