The terms 'antioxidant', 'oxidative stress' and 'oxidative damage' are widely used but rarely defined. This brief review attempts to define them and to examine the ways in which oxidative stress and oxidative damage can affect cell behaviour both in vivo and in cell culture, using cancer as an example.

Biochemistry of oxidative stress

Decades of study indicate that copper oral exposures are typically not a human health concern. Ingesting high levels of soluble copper salts can cause acute gastrointestinal symptoms and, in uncommon cases, liver toxicity in susceptible individuals with repeated exposure. This focused toxicological review evaluated the current literature since the last comprehensive reviews (2007–2010). Our review identified limitations in the existing United States and international guidance for determining an oral reference dose (RfD) for essential metals like copper. Instead, an alternative method using categorical regression analysis to develop an optimal dose that considers deficiency, toxicity, and integrates information from human and animal studies was reviewed for interpreting an oral RfD for copper. We also considered subchronic or chronic toxicity from genetic susceptibility to copper dysregulation leading to rare occurrences of liver and other organ toxicity with elevated copper exposure. Based on this approach, an oral RfD of 0.04 mg Cu/kg/day would be protective of acute or chronic toxicity in adults and children. This RfD is also protective for possible genetic susceptibility to elevated copper exposure and allows for background dietary exposures. This dose is not intended to be protective of patients with rare genetic disorders for copper sensitivity within typical nutritional intake ranges, nor is it protective for those with excessive supplement intake. Less soluble mineral forms of copper in soil have reduced bioavailability as compared with more soluble copper in water and diet, which should be considered in using this RfD for risk assessments of copper.

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Critical Review of Exposure and Effects: Implications for Setting Regulatory Health Criteria for Ingested Copper.

Copper and Zinc Dysregulation in Alzheimer’s Disease

Meat flavour in pork and beef – From animal to meal

Visible absorbance spectroscopy is a widely used tool in chemical, biochemical, and medical laboratories. The theory and methods of absorbance spectroscopy are typically introduced in upper division undergraduate chemistry courses, but could be introduced earlier with the right curriculum and instrumentation. A major challenge in teaching spectroscopy is gaining access to laboratory equipment, which can be expensive. Even common educational spectrophotometers still carry a substantial cost and have the disadvantage of being inherently closed designs. We report on a 3D-printable smartphone spectrophotometer that is very inexpensive to build, yet retains the functionality and analytical accuracy necessary to teach concepts like the Beer–Lambert Law. The optical components are arranged in an intuitive, accessible way so that students can see each relevant part and experiment with the parameters. Here, we describe the device and provide exercises to teach different concepts in analytical spectrophotometry.

Teaching UV–Vis Spectroscopy with a 3D-Printable Smartphone Spectrophotometer

The multiple Maillard reactions of ribose and deoxyribose sugars and sugar phosphates

An important metabolite in nucleotide synthesis, ribose 5-phosphate (R5P) undergoes Maillard reactions at a rate significantly faster than most common sugars and sugar phosphates of its type. At pH = 8 and 37 degrees C, R5P reacts with amino acids to generate UV-absorbing compounds within hours and brownish compounds within a day. The increased rate can be attributed to the strategic location of the 5-phosphate group near the reactive C1 center. As expected, the rate of reaction is at least partially related to pKa of the attacking amine and it follows first-order kinetics in respect to amine (in the case of glycine). In terms of producing 280 nm absorbing compounds, the reaction order in respect to R5P was 1.5. The reaction mechanism appears to proceed through a 1-deoxyribosome intermediate. In reactions with proteins, R5P exhibits an ability to promote cross-linking.

Maillard reactions of ribose 5-phosphate and amino acids.

Ribose sugars generate internal glycation cross-links in horse heart myoglobin.

Extensive research has linked the amyloid-beta (Aβ) peptide to neurological dysfunction in Alzheimer's disease (AD). Insoluble Aβ plaques in the AD patient brain contain high concentrations of advanced glycation end-products (AGEs) as well as transition metal ions. This research elucidated the roles of Aβ, sugars, and Cu2+ in the oxidative stress mechanism of AD at the molecular level. Mass spectral (MS) analysis of the reactions of Aβ with two representative sugars, ribose-5-phosphate (R5P) and methylglyoxal (MG), revealed Lys-16 and Arg-5 as the primary glycation sites. Quantitative analysis of superoxide [Formula: see text] production by a cyt c assay showed that Lys-16 generated four times as much [Formula: see text] as Arg-5. Lys-16 and Arg-5 in Aβ1-40 are both adjacent to histidine residues, which are suggested to catalyze glycation. Additionally, Lys-16 is close to the central hydrophobic core (Leu-17-Ala-21) and to His-13, both of which are known to lower the pKa of the residue, leading to increased deprotonation of the amine and an enhanced glycation reactivity compared to Arg-5. Gel electrophoresis results indicated that all three components of AD plaques-Aβ1-40, sugars, and Cu2+-are necessary for DNA damage. It is concluded that the glycation of Aβ1-40 with sugars generates significant amounts of [Formula: see text], owing to the rapid glycation of Lys-16 and Arg-5. In the presence of Cu2+, [Formula: see text] converts to hydroxyl radical (HO·), the source of oxidative stress in AD.

Glycation of Lys-16 and Arg-5 in amyloid-β and the presence of Cu 2+ play a major role in the oxidative stress mechanism of Alzheimer's disease

Guanosine derivatives with a nucleophilic group at the 5′ position (G-5′) are oxidized by the PtIV complex Pt(d,l)(1,2-(NH2)2C6H10)Cl4 ([PtIV(dach)Cl4]). The overall redox reaction is autocatalytic, consisting of the PtII-catalyzed PtIV substitution and two-electron transfer between PtIV and the bound G-5′. In this paper, we extend the study to improve understanding of the redox reaction, particularly the substitution step. The [PtII(NH3)2(CBDCA-O,O′)] (CBDCA = cyclobutane-1,1-dicarboxylate) complex effectively accelerates the reactions of [PtIV(dach)Cl4] with 5′-dGMP and with cGMP, indicating that the PtII complex does not need to be a PtIV analogue to accelerate the substitution. Liquid chromatography/mass spectroscopy (LC/MS) analysis showed that the [PtIV(dach)Cl4]/[PtII(NH3)2(CBDCA-O,O′)]/cGMP reaction mixture contained two PtIVcGMP adducts, [PtIV(NH3)2(cGMP)(Cl)(CBDCA-O,O′)] and [PtIV(dach)(cGMP)Cl3]. The LC/MS studies also indicated that the trans,cis-[PtIV(dach)(37Cl)2(35Cl)2]/[PtII(en)(35Cl)2]/9-...

Roger K. Sandwick

Papers

The multiple Maillard reactions of ribose and deoxyribose sugars and sugar phosphates

Maillard reactions of ribose 5-phosphate and amino acids.

Ribose sugars generate internal glycation cross-links in horse heart myoglobin.

Glycation of Lys-16 and Arg-5 in amyloid-β and the presence of Cu 2+ play a major role in the oxidative stress mechanism of Alzheimer's disease

Importance of platinum(II)-assisted platinum(IV) substitution for the oxidation of guanosine derivatives by platinum(IV) complexes.