Micronutrients
Chuong Pham-Huy, Bruno Pham Huy in Food and Lifestyle in Health and Disease, 2022
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.
Oxidative Stress and the Effects of Dietary Supplements on Glycemic Control in Type 2 Diabetes
Emmanuel C. Opara, Sam Dagogo-Jack in Nutrition and Diabetes, 2019
Blood glucose regulation is dependent upon normal glucose metabolism, which, in turn, is regulated by chains of reactions catalyzed by enzymes. Some enzymes require no chemical groups other than their amino residues for activity, and others require an additional chemical component referred to as a cofactor. The cofactor may be either one or more inorganic ions or a complex organic or metallorganic molecule called a coenzyme. Certain enzymes require both a coenzyme and one or more metal ions for activity. These metal ions are usually transition metals, which are obtained from the diet in small (micrograms and milligrams) amounts, hence the term trace elements. As already mentioned, some of these elements are present in the cells and tissues as cofactors of certain antioxidant enzymes, such as zinc in superoxide dismutase (SOD) and selenium in glutathione peroxidase (GPx). As transition metals, the trace elements have antioxidant potential, and the effect of supplementation with certain trace elements on glycemic control has been examined in diabetic patients.
Introduction
Emmanuel Opara in NUTRITION and DIABETES, 2005
Blood-glucose regulation is dependent upon normal glucose metabolism, which, in turn, is regulated by chains of reactions catalyzed by enzymes. Some enzymes require no chemical groups for activity other than their amino residues, and others require an additional chemical component referred to as a cofactor. The cofactor may be either one or more inorganic ions or a complex organic or metallorganic molecule called a coenzyme. Certain enzymes require both a coenzyme and one or more metal ions for activity. These metal ions are usually transition metals, which are obtained from the diet in small (micrograms and milligrams) amounts, hence the term trace elements. As already mentioned, some of these elements are present in the cells and tissues as cofactors of certain antioxidant enzymes, such as zinc in superoxide dismutase (SOD) and selenium in glutathione peroxidase (GPx). As transition metals, the trace elements have antioxidant potential, and the effect of supplementation with certain trace elements on glycemic control has been examined in diabetic patients.
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.
Design, synthesis, and evaluation of 3,7-substituted coumarin derivatives as multifunctional Alzheimer’s disease agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Sheunopa C. Mzezewa, Sylvester I. Omoruyi, Luke S. Zondagh, Sarel F. Malan, Okobi E. Ekpo, Jacques Joubert
Similarly, in contrast to MAO-A, the elongated nature of the MAO-B active site allows for better accommodation of the 3-propargylamine derivatives 6 and 7. It was observed that both compounds were able to interact with the crucial flavin adenine dinucleotide (FAD) cofactor to varying extents due to the inclusion of the propargylamine moiety. The FAD cofactor is essential for substrate catalysis and thus compounds that can come into close proximity or bind to this cofactor are known to inhibit the enzyme function to a greater extent42. Compound 6 maintains the previously mentioned π–H bonding with Cys 172 as well as its propargylamine moiety orienting in close proximity to FAD. Compound 7’s propargylamine moiety forms crucial π–H bonds with the cofactor. From the low nanomolar IC50 and high SI values displayed by these compounds, the importance of the propargylamine moiety can be seen in its ability to produce highly potent and selective inhibitors of MAO-B (Figure 7) .
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].
Related Knowledge Centers
- Biochemistry
- Catalysis
- Chemical Compound
- Chemical Reaction
- Enzyme
- Enzyme Kinetics
- Ligand
- Organic Compound
- Protein
- Inorganic Ions