Enzyme/transporter multiplicative effect

Another molecular mode of action of furanocoumarins is related with protein modification. Proteins have multiple functions enzymes, transporters, ion channels, receptors, microtubules, structural proteins, etc. Conformational changes alter their properties and can prevent effective cross talk between proteins themselves and between proteins and other targets. Polyphenols can interact with proteins by forming hydrogen bonds and ionic bonds with electronegative atoms of the peptide bond or the positively charged side chains of basic amino acids, respectively. 

Fig-1 The final NM-induced toxic effect observed in vitro is the result of multiple processes (1) interaction with proteins (formation of the protein corona, activation/inactivation of enzymes) (2) dissolution and release of toxic ions (3) production of ROS at the NMs surface (4) aggregation/agglomeration (5) diffusion and sedimentation that influence NM transport to the cell layer and the final effective concentration (6) interaction with the cell membrane and membrane receptors (activation/inhibition) (7) cell uptake (including receptor-mediated endocytosis and other uptake mechanisms) (8) interaction with intracellular enzymes (activation/inhibition) (9) production of intracellular ROS (10) activation of transcription factors and (11) binding to nucleic acids and genotoxicity, among others. Processes (1)—(5) are closely interconnected. The resulting effect observed is the result of the composite rate of all these different reactions... 

Encapsulation of enzymes in LMs offers further improvements for immobilization of complex enzyme systems, as the enzymes / cofactors, etc. are situated in aqueous droplets surrounded by a stable liquid hydrocarbon film (Figure 1). Instead of the physical pores present in microcapsules, the HC barrier, which has a diffusion thickness of about 0.1-1.0 p, effectively blocks all molecules except those which are oil-soluble or transportable by the selected carriers. Encapsulation of enzymes in LMs is accomplished simply by emulsifying aqueous enzyme solutions. Hence, LMs offer many advantages over other systems used for separation and eirzyme immobilization they are inexpensive and easy to prepare they promote rapid mass transport they are selective for various chemical species they can be disrupted (demulsified) for recovery of internal aqueous solutions gradients of pH and concentration (even of small molecules) can be maintained across the HC barrier multiple enzyme / cofactor systems can be coencapsulated and enzymatic reaction and separation can be combined. Some of the potential disadvantages of LMs for enzyme encapsulation have been discussed earlier. 

The inhibitory effects of the pyrrolinone derivatives were evaluated using enzyme inhibition and cellular activation assays. Compound 6 (Fig. 4.3-5) showed an IC50 of 10 nM, compared to 0.6 nM for the related peptide inhibitor 5 (L682,679). However, the synthetic agent 6 showed better cell transport capacity. In a cellular antiviral assay, 5 and 6 showed CIC95 values (the concentration that inhibits 95% of virus multiplication in the cellular cultures) of 6.0 and 1.5 pM, respectively. Smith and Hirschmann proposed that the improved cellular uptake properties of polypyrrolinones are due to a reduction in the inhibitor solvation. Solvation is an impediment to transport because extraction of a molecule into a lipid bilayer from an aqueous phase is... 

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