Hypoxia inducible factors (HIFs) play vital roles in cellular maintenance of oxygen homeostasis. These transcription factors are responsible for the expression of genes involved in angiogenesis, metabolism, and cell proliferation. Here, we generate a detailed mathematical model for the enzyme kinetics of α-ketoglutaratedependent HIF prolyl 4-hydroxylase domain (PHD) dioxygenases to simulate our...

Activated macrophages undergo metabolic reprogramming, which drives their pro-inflammatory phenotype, but the mechanistic basis for this remains obscure. Here, we demonstrate that upon lipopolysaccharide (LPS) stimulation, macrophages shift from producing ATP by oxidative phosphorylation to glycolysis while also increasing succinate levels. We show that increased mitochondrial oxidation of succ...

Lactate dehydrogenase isozyme 5 from rabbit skeletal muscle is activated by citrate, cis-aconitate, isocitrate, alpha-ketoglutarate, succinate, fumarate, malate, aspartate, and glutamate. In the presence of these activators the shape of the pyruvate saturation curve is changed from sigmoid to hyperbolic. Lactate dehydrogenase isozyme 1 from rabbit heart gives a hyperbolic pyruvate saturation cu...

The production of 1,3-propanediol (1,3-PD) from glycerol by Klebsiella pneumoniae is limited synthesis numerous byproducts. Among them, the accumulation acetate has largest negative impact on fermentation performance. To address overflow caused knocking out lactate dehydrogenase, alcohol dehydrogenase and succinate several metabolic engineering manipulations were conducted. First, was reduced t...

Following traumatic brain injury, complex cerebral energy perturbations occur. Correlating with unfavourable outcome, high brain extracellular lactate/pyruvate ratio suggests hypoxic metabolism and/or mitochondrial dysfunction. We investigated whether focal administration of succinate, a tricarboxylic acid cycle intermediate interacting directly with the mitochondrial electron transport chain, ...

Escherichia coli NZN111, which lacks activities for pyruvate-formate lyase and lactate dehydrogenase, and AFP111, a derivative which contains an additional mutation in ptsG (a gene encoding an enzyme of the glucose phophotransferase system), accumulate significant levels of succinic acid (succinate) under anaerobic conditions. Plasmid pTrc99A-pyc, which expresses the Rhizobium etli pyruvate car...

The effect of temperature on the activation energies of mitochondrial enzymes of the yeast Saccharomyces cerevisiae was examined. Non-linear Arrhenius plots with discontinuities in the temperature range 14-19 degrees C and 19-22 degrees C were observed for the respiratory enzymes and mitochondrial ATPase (adenosine triphosphatase) respectively. A straight-line Arrhenius plot was observed for th...

The mammalian enzyme system which catalyzes the aerobic oxidation of succinic acid has been shown by Keilin and Hartree (1) to consist of succinic dehydrogenase and the complete cytochrome system. Although cytochrome oxidase is generally considered to be the universal catalyst of all respiring cells (2), it has been reported to be absent from, or present in small amounts in, several aerobic org...

Hypoxia inducible factors (HIFs) play vital roles in cellular maintenance of oxygen homeostasis. These transcription factors are responsible for the expression of genes involved in angiogenesis, metabolism, and cell proliferation. Here, we generate a detailed mathematical model for the enzyme kinetics of α-ketoglutarate-dependent HIF prolyl 4-hydroxylase domain (PHD) dioxygenases to simulate ou...

introduction: recently depleted uranium is being widely used as anti-armour ammunition and at very high temperature, results in information of an aerosol of very small uranium oxide particles, which may be inhaled. it is alleged that these particles represent a new battlefield hazard because of the chemical toxicology and/or radioactivity. method & materials: male wistar strain albino rats were...