Modulating factors esters

Another factor affecting drug stability is electrical current. The stability of hydrocortisone hemisuccinate and phosphate esters as their sodium salts was affected by a change in pH that occurred when current was applied during an iontophoresis study.506 Degradation of propranolol hydrochloride in an electrically modulated drug delivery device has been reported.507... 

The LDL receptor is a key component in the feedback-regulated maintenance of cholesterol homeostasis [1]. In fact, as an active interface between extracellular and intracellular cholesterol pools, it is itself subject to regulation at the cellular level (Fig. 2). LDL-derived cholesterol (generated by hydrolysis of LDL-bome cholesteryl esters) and its intracellularly generated oxidized derivatives mediate a complex series of feedback control mechanisms that protect the cell from over-accumulation of cholesterol. First, (oxy)sterols suppress the activities of key enzymes that determine the rate of cellular cholesterol biosynthesis. Second, the cholesterol activates the cytoplasmic enzyme acyl-CoA cholesterol acyltransferase, which allows the cells to store excess cholesterol in re-esterified form. Third, the synthesis of new LDL receptors is suppressed, preventing further cellular entry of LDL and thus cholesterol overloading. The coordinated regulation of LDL receptors and cholesterol synthetic enzymes relies on the sterol-modulated proteolysis of a membrane-bound transcription factor, SREBP, as described in Chapter 14. 

Angel, P., Imagawa, M., Chiu, R., Stein, B., Imbra, R. J., Rahmsdorf, H. J., Jonat, C., Herrlich, P., and Karin, M. (1987). Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell (Cambridge, Mass.) 49,729-739. 

The pH of the reaction medium is another important factor for modulating both the activity and enantioselectivity of Lipase OF. The enzyme showed optimal hydrolysis activity at pH 4.0, while the enantioselectivity increased sharply with the decrease in medium pH from 4.0 to 2.2. Based on spectroscopic studies, the enhancement of the lipase activity and enantioselectivity at the lower pH could be attributed to the changes in the flexible and sensitive conformation of the lipase induced by tuning the biocatalyst microenvironment. Using a hybrid strategy by modulating pH and surfactant, enantiomer-enriched (5)-ketoprofen could be obtained with 95.5% ee and 39.1% yield from rac-ketoprofen chloroethyl ester (100 mM) at pH 2.5 in the presence of 0.5% (w/v) Tween-80 as a modulator. ... 

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