701 research outputs found
Oncometabolites: tailoring our genes
Increased glucose metabolism in cancer cells is a phenomenon that has been known for over 90Ā years, allowing maximal cell growth through faster ATP production and redistribution of carbons towards nucleotide, protein and fatty acid synthesis. Recently, metabolites that can promote tumorigeneis by altering the epigenome have been identified. These āoncometabolitesā include the tricarboxylic acid cycle metabolites succinate and fumarate, whose levels are elevated in rare tumours with succinate dehydrogenase and fumarate hydratase mutations, respectively. 2-Hydroxyglutarate is another oncometabolite; it is produced deĀ novo as a result of the mutation of isocitrate dehydrogenase, and is commonly found in gliomas and acute myeloid leukaemia. Interestingly, the structural similarity of these oncometabolites to their precursor metabolite, Ī±-ketoglutarate, explains the tumorigenic potential of these metabolites, by competitive inhibition of a superfamily of enzymes called the Ī±-ketoglutarate-dependent dioxygenases. These enzymes utilize Ī±-ketoglutarate as a cosubstrate, and are involved in fatty acid metabolism, oxygen sensing, collagen biosynthesis, and modulation of the epigenome. They include enzymes that are involved in regulating gene expression via DNA and histone tail demethylation. In this review, we will focus on the link between metabolism and epigenetics, and how we may target oncometabolite-induced tumorigenesis in the future
Electrochemistry and application of a novel monosubstituted squarate electron-transfer mediator in a glucose oxidase-doped poly(phenol) sensor
Electrosynthetic poly(phenol) nanofilms were deposited in situ on platinum electrodes
in the presence and absence of glucose oxidase. The synthesis charges and currents of
the nonconducting polymer films were recorded at various applied potentials for films grown
from 25ā100 mM phenol concentrations. Film parameters such as the standard rate constant
for film deposition, film thickness, and surface concentration of the poly(phenol) films were
evaluated from the cyclic and step voltammograms of the polymerization process. A novel
electron-transfer mediator consisting of monosubstituted 4-hydroxycyclobut-3-ene-1,2-dione
(squarate) was used as a mediator for Pt/poly(phenol) nano-film/GOx amperometric glucose
biosensors. Amperometric responses for 3-diphenylamino-4-hydroxycyclobut-3-ene-1,2-
dione (diphenylaminosquarate: EĀ°ā² = of +328 mV/Ag-AgCl at pH 7.0)-mediated systems
were measured by both steady-state amperometric and cyclic voltammetry. The sensor sensitivity
was calculated to be 558 nA cm
ā2
(ĀµM)
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