Receptors metabolic sensors

Biosensors for inhibitor determination are based on the ability of inhibiting substances to become bound to the receptor component and decelerate the substrate conversion. Therefore, inhibitor sensors, similar to apoenzyme sensors and immunosensors, combine the affinity principle with enzymatic amplification reactions. In contrast to metabolism sensors, the binding is evaluated rather than the chemical reaction of the analyte. 

In contrast, metabolic sensors have the advantage to regenerate their affinity structures by themselves, because the substrate S is converted to the product P, which has a different affinity to the receptor, in this case an enzyme E. The response of enzyme-based sensors is induced by the production of P, and follows the Michaelis-Menten kinetics. The simplest case is the reversible formation of an. intermediate complex SE, which then decomposes with a velocity constant k to the product. The affinity constant in this case, called the Michaelis constant is an expression of the substrate concentration, at which half the maximum... 

Depending upon the mechanism of biochemical interaction between the receptor and the analyte, two basic types of biosensors can be distinguished biocatalytic (metabolic) sensors, and bio-affinity sensors (Table 18). 

The linear measuring range for metabolic sensors depends on the apparent Michaelis-Menten constant (/fMapp) of the immobilized enzyme (not free in solution and approachable from all directions, thus, apparent ). which describes a particular substrate concentration associated with half the maximum rate of the enzyme reaction. The reaction rate of an immobilized receptor enzyme is controlled by the rate of substrate and product diffusion through both the semiper-meable membrane covering the enzyme and the layer of immobilized enzyme itself, resulting in a... 

Another example in which literature results were reanalyzed in view of the PSSC concept concerns the development of ligands for the farnesoid X receptor. The farnesoid X receptor is a transcriptional sensor for bile acids, the primary products of cholesterol metabolism, and plays an important role in lipid homeostasis. The farnesoid X receptor was, until recently, an orphan receptor, which means that no specific ligands existed for this receptor. Selective ligands for this receptor have been found in natural product libraries described by Nicolaou et al. The group of Nicolaou developed solid phase synthesis methods to make combinatorial libraries based on a benzopyran core structure. " A 10,000-membered combinatorial library based on the benzopyran core structure was synthesized and screened for activity on the farnesoid X receptor. The first specific ligands for the... 

Iron Regulatory Proteins 1 and 2 (IRPl and 2) are Important Cytosolic Iron Sensors that Regulate Expression of Ferritin, Transferrin Receptor and Other Iron Metabolism Proteins... 

Receptors/sensors involved in regulation of xenobiotic-metabolizing enzymes... 

Latruffe, N., M. Cherkaoui-Malki, V. Nicolas-Frances, B. Jannin, M.-C. Clemencet, F. Hansmannel, P. Passilly-Degrace and J.-P. Berlot. Peroxisome-proliferator-activated receptors as physiological sensors of fatty acid metabolism molecular regulation in peroxisomes. Biochem. Soc. Trans. 29 305-309, 2001. 

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