overexpression of HXK1 in a highly modified strain of Yarrowia lipolytica W29 engineered to optimize oil production, combined with Saccharomyces cerevisiae invertase gene expression. For the recombinant strain, sucrose is a better substrate than either of its building blocks, glucose or fructose. Over its 96 h of growth in the bioreactors, this strain produces 9.15g/l of lipids, yielding 0.262g/g of biomass
high-throughput assay for screening small molecule collections to identify inhibitors of the Plasmodium falciparum hexokinase. The assay employs an ADP-GloTM reporter system in a 1536-well plate format, is robust with a signal-to-background of 3.4, a percent coefficient of variation of 6.8 and a Z'-factor of 0.75
given the combined prominent role of glucokinase on insulin secretion and hepatic glucose metabolism where the GK-GKRP mechanism is involved, activation of glucokinase has a new therapeutic potential in the treatment of type 2 diabetes
HK II inhibitors may be therapeutically useful for the treatment of advanced infiltrative hypovascular hepatocellular carcinomas, which are growing in a hypoxic environment
glucokinase is a potential therapeutic target for treating maturity-onset diabetes of the young and persistent hyperinsulinemic hypoglycemia of infancy
endogenous glucokinase expression correlates with O-GlcNAc levels in the pathophysiological model of type II diabetes, ob/ob mice. In response to the pharmacological inhibition of O-GlcNAcase, contents of glucokinase increase. Glucokinase is modified by O-GlcNAcylation. siRNA-mediated O-linked N-acetylglucosamine transferase knock-down not only decreases O-GlcNAc content but also glucokinase protein level
hexokinase is distributed in the worm extensively as well as in liver tissue and serum from infected rats. High-level specific IgG1 and IgG2a are induced in rats by immunization with recombinant enzyme. The enzymatic activity of hexokinase is suppressed by the antibodies in vitro, and the survival of Clonorchis sinensis is inhibited by the antibodies in vivo and in vitro
hexokinase-II binds to the voltage-dependent anion channel located on the mitochondrial outer membrane. When bound, hexokinase-II is blocking a major cell death pathway. A series of truncations and point mutations to the N-terminal end of hexokinase-II identify the binding site to the channel within the first 10 amino acids
HIV-1 induces a robust increase in hexokinase-1 expression. Hexokinase enzymatic activity is significantly inhibited in HIV-1 infected peripheral blood mononuclear cells and in phorbol 12-myristate 13-acetate differentiated U1 cells. Increased levels of mitochondria-bound hexokinase -1are observed in phorbol 12-myristate 13-acetate-induced U1 cells and in the HIV-1 accessory protein, viral protein R transduced U937 cell derived macrophages. Dissociation of hexokinase-1 from mitochondria in U1 cells using clotrimazole induces mitochondrial membrane depolarization and caspase-3/7 mediated apoptosis. Dissociation of hexokinase-1 from mitochondria in viral protein R transduced U937 also activates caspase-3/7 activity
in cancer cells, elevated hexokinase-2 expression is induced by activated PI3K/Akt signaling. Hexokinase-2 is overexpressed in 83.3% of specimens detected and is closely correlated with Ki67, a cell proliferation index. Silencing of endogenous hexokinase-2 results in decreased aerobic glycolysis. Inhibition of PI3K/Akt signaling also suppresses aerobic glycolysis and this effect can be reversed by reintroduction of hexokinase-2. Knockdown of HK2 leads to increased cell apoptosis and reduced ability of colony formation
mutations A379S, D400Y, E300A, E395A, E395G, H380N, I348N, L301M, M298I, M381G, M402R, R308K, R394P, R397S, and S398R are observed in 12 different patients with type 2 diabetic condition. The structural analysis of these mutated GKs shows a variable number of beta-alpha-beta units, hairpins, beta-bulges, strands, helices, helix-helix interactions, beta-turns, and gamma-turns along with the RMSD variations when compared to wild-type GK. The substrate shows variable binding orientations and cannot fit into the active site of these mutated structures, it is expelled out of the conformations
the peptidoglycan of Lactobacillus casei shows cytotoxic activity against various tumour cells. A synthetic peptide derived from the peptidoglycan impairs the entire metabolism of cultured tumour cells and restores the apoptotic process. Normal cells appear to be stimulated rather than inhibited by the peptide. The pentapeptide binds with the hexokinase and exerts a weak inhibitory effect on hexokinase enzymatic specific activity. in tumour cells, a percentage of peptide is partially blocked by the cytosolic hexokinase and the remaining is available to bind with the mitochondrial-bound hexokinase. This binding triggers the Bax-induced proapoptotic process including a decrease in succinate dehydrogenase activity, cellular ATP and mitochondrial membrane potential, as well as changes in the voltage dependent anion channel structure on the outer mitochondrial membrane and cytochrome C release. As the final stage, the antiapoptotic process is suppressed, the cellular functions are altered and the cell is destroyed