The Biological Role Of Isoketals

Alan Diamond’s laboratory at the University of Illinois at Chicago as an intern. My research focused on the effect of DNA variations and selenium supplementation on the expression of the antioxidant, Glutathione Peroxidase 1 (GPx-1). By western blot analysis, I found that selenium, a nutritional supplement, increased GPx-1 expression in human-derived cell lines. In addition, using the Seahorse XF Analyzer, I determined that GPx-1 induction led to a decreased rate of glycolysis. The Seahorse simultaneously measures oxygen consumption and changes in acidity. Particularly amazing to me was the ability of the instrument to analyze and collect data on living and breathing cells in real time. Interestingly, the decreased rate of glycolysis upon GPx-1 induction correlated with a reduced expression of Lactate Dehydrogenase (LDH), a key enzyme upregulated in cancer. The results suggest that increased GPx-1 expression and consequent reduction in glycolysis may help to slow cancer cell growth. The next steps would be to extend the findings to animal models. I believe this work may have translational applications for treating patients with

Isoamyl acetate was synthesized by refluxing 1 eq of isopentanol with 4 eq of acetic acid, and 0.5 eq of concentrated sulfuric acid as a catalyst and a dehydrating agent to ensure reaction equilibrium lies far towards the products. The reaction mixture was then added to water and liquid-liquid extraction was conducted. A second extraction was then conducted after adding NaHCO3 solution to the organic layer. This removes the residual acids which are soluble in the aqueous layer. Drying of the crude ester with anhydrous MgSO4 removes H2O that disrupts the NMR and infrared spectrum, hindering the characterization of the product formed.

Molecular Sciences reveal the irreversible non-enzymatic degradation of lycopene with various oxidative metabolites. The blood plasma levels get affected by the accumulation of 3-keto-apo-B and 1515-apo lycopenoids among cleavage products.(64) Certain dietary factors consistently influence heart related diseases by the concentration of plasma levels with no specific components. The Hyper-reactivity of ROS and Nitric Oxide generation endogenously affect metabolic activities throughout the critical stages of DNA, lipids and proteins. The blood circulation containing Chylomicrons and other Apo-beta lipoproteins need a constant Sophisticate Replenishment System for internal absorption and enzymatic pathways on human cells and tissues.

As you may know, antioxidants promote good health as they help avoid diseases. More specifically, antioxidants help slow down the oxidation of cells in our body. When cells oxidize, they generate free radicals, which are also known as cellular bi-products. It is perfectly safe to have a manageable amount of these free radicals in the body. However, when the free radicals are in excess, they can wreak havoc on our organism's cellular

Both types of the aconitase can catalyze the interconversion of citrate and isocitrate. However, for the cytosolic aconitase, it can accelerate the reaction in the cytoplasm as an alternative, unlike the mitochondrial aconitase which proceeds the reaction inside of the mitochondrion. In addition to that, the cytosolic aconitase has the specific feature of balancing the number of acetyl-CoA and NADPH synthesized during the citric acid cycle. As the result of this, the other metabolisms can use these two compounds to generate other essential compounds, such as amino acids and fatty acids. Even though, the cytosolic aconitase can only be active in catalysis when the level of the iron atoms in the cytosol is high under normal circumstances. Otherwise, the cluster with four iron atoms and four sulfur atoms will be detached from the cytosolic aconitase, losing the role of being an enzyme. (McDowall,

To affirm that the theorized mechanism of halogenation for sulfilimine bond formation they tested the ability of peroxidasin to form crosslinks in the absence of halides. As expected minimal crosslinking occurred, and it was supported that crosslinks formed as a result of halogenation. The rest of figure 3 investigates the role of peroxidase in hypohalous acid production specifically; HBr and HCl. Different peroxidases showed preferentiality in which hypohalous acid they formed.

In this journal entry it states “receiving experimental exposure of rotenone for 24h to study the oxidative stress-induced cytotoxicity and apoptotic cell death in human liver cells-HepG2, the result shows that there is a deficiency in cellular antioxidant defenses, glutathione, catalase, and superoxide dismutase levels”. (3) The specific aim of this research is to understand how enzyme work within our body and what causes them to become faulty, with the right knowledge and studies there might be a chance that one day enzyme can be transform into its original state which will help cure diseases such diabetes, Alzheimer, and other incurable

This free radical, which is initially formed as relatively unreactive, reacts very rapidly with oxygen to yield a highly reactive trichloromethyl peroxy radical (CCl3OO•). Both radicals are capable of binding to proteins or lipids, or abstracting a hydrogen atom from an unsaturated lipid, thus, initiating lipid peroxidation (Halliwell, and Gutteridge, 1990; Williams, and Burk, 1990; Lee, and Jeong, 2002). Lipid peroxidation may cause peroxidative tissue damage in inflammation, cancer, aging, ulcer, cirrhosis, and atherosclerosis. Therefore, inhibition of the cytochrome P450-dependent oxygenase activity could cause a reduction in the level of toxic reactive metabolites and a decrease in tissue injury. On the other hand, an elevation of plasma AST and ALT activities could be regarded as a sign of damage to the liver cell

IsoKs react covalently to lysyl residues of proteins to form a stable adduct and intramolecular cross-links (Iyer, Ghosh et al. 1989, Boutaud, Brame et al. 1999, Brame, Salomon et al. 1999). These molecules react at a rate that far exceeds other well studied products of lipid peroxidation, including 4-hydroxynonenal (4-HNE) (Brame, Salomon et al. 1999) (Fig. 1.3A). Results from in vitro oxidation of arachidonic acid strongly suggests that IsoKs form in vivo; however when tissues such as plasma and urine, IsoKs were not detected, although significant quantities of F2-IsoPs were detected by GC/MS. Analysis of iron/ADP/ascorbate treated liver microsomes also failed to detect any IsoKs, despite containing abundant F2-IsoPs. The reason for the failure to detect IsoKs in biological samples became apparent when studies were carried out to quantify the reactivity of IsoKs with proteins.

Absence of GDH, mitochondrial matrix enzyme indicates that amino acids are not important oxidative substrates

Glutathione helps to protect cells from reactive oxygen species. GSH checks free radical damage and helps detoxification by conjugating with chemicals. Increase in reactive oxygen species protection causes GSH depletion. GSH acts as cofactor for Glutathione Peroxidase (GPx) and Glutathione-S-transferase (GST). Glutathione-S-transferase is thought to play a physiological role in initiating the detoxification and these enzymes catalyse the reaction of such compounds with the -SH group of glutathione, thereby neutralizing their electrophilic sites and rendering the products more water-soluble. GPx is present throughout the tissues as four different isoenzymes, cellular, extracellular glutathione peroxidase, as phospholipid hydroperoxide glutathione peroxidase and gastrointestinal glutathione peroxidase (Alam et al 2013). GPx low activity is one of the early consequences of a disturbance of the prooxidant or antioxidant balance due to toxic exposure. Glutathione reductase plays an important role in maintaining a basic GSH pool, via catalysing the reduction of glutathione disulfide (GSSG) to GSH in NADPH-dependent reaction (Yao Chen et al

Oxidative stress has been implicated in various pathophysiological conditions either directly or indirectly. They are cardiovascular disease, cancer (1), neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s diseases (AD) (2,3), Amyotrophic lateral sclerosis (ALS), Huntington’s disease, and multiple sclerosis, Diabetes Mellitus (4), ischemia/reperfusion, fibrosis, Kidney disease, impairment via cochlear damage induced by elevated sound levels, ototoxicity of drugs such as cisplatin, and in congenital deafness in both animals and humans, obstructive sleep apnea, obesity, hypertension, diseases of prematurely and other diseases related to ageing (5). These diseases fall into two groups.

CYP2E1 is a major cytochorme found to be involved in carbon-chlorine bond reductive cleavage and biotransformation of CCl4 to trichloromethyl radical (CCl3•). These cytochrome systems catalyze many reactions involved in drug metabolism and synthesis of cholesterol and other lipid metabolites both in endogenous substrates, such as ethanol and acetone as well as exogenous substrates which includes carbon tetrachloride (Tang et al., 2013). In the presence of oxygen, CCl3• generates the highly reactive metabolites such as trichloromethyl peroxy (CCl3OO•) free radicals which covalently bind to the cellular macromolecules, lipids and polyunsaturated fatty acids in the cellular membrane. Trichloromethyl peroxy (CCl3OO•) free radicals react with suitable substrates to complete its electron pair. CCl3OO• is

Several metabolites, molecules generated and used in intermediate steps of metabolic reactions, have been shown to slow the aging process and are of great interest to researchers because the mechanisms of how they do this is unknown. This project is a deeper dive into a specific molecule that was of particular interest to the research team during a screening of many endogenous molecules including metabolites and disease-associated metabolites. In this study, α-ketoglutarate (α-KG) is explored in order to determine if and how it effects the lifespan of adult Caenorhabditis elegans, also known as roundworms. α-KG is an important molecule in cellular respiration, particularly the citric

Abstract: Atherosclerosis is a disease in which plaque builds up inside the arteries. Arteries are blood vessels that carry oxygen-rich blood to the heart and other parts of the body. Reactive oxygen species are common by-products of many oxidative biochemical and physiological processes. They can be released by NAD(P)H oxidase, nitric oxide synthase and xanthine oxidase and activates various signaling pathways that underlie vascular inflammation in atherogenesis thus leading to oxidative stress induced tissue injury. Therefore, it is important to consider the sources of oxidants in the context of available antioxidants such as ascorbic acid, tocopherol, β-carotene, superoxide