Kinetic parameters (k(inact) and K(I)) obtained in microsomes are often used to predict time-dependent inactivation. We previously reported that microsomal inactivation kinetic parameters of diltiazem underpredicted CYP3A inactivation in hepatocytes. In this study, we evaluated the contributions of inactivation and reversible inhibition of CYP3A by diltiazem and its N-desmethyl (MA) and N,N-did...

The targeted inactivation of oncogenes may be a specific and effective treatment for cancer. However, because human cancers are the consequence of multiple genetic changes, the inactivation of one oncogene may not be sufficient to cause sustained tumor regression. Moreover, cancers are genomically unstable and may readily compensate for the inactivation of a single oncogene. Here we confirm by ...

Protein tyrosine phosphatases (PTPs) are cysteine-dependent enzymes that play a central role in cell signaling. Organic hydroperoxides cause thiol-reversible, oxidative inactivation of PTP1B in a manner that mirrors the endogenous signaling agent hydrogen peroxide.

The reversible inactivation of tobacco mosaic virus by crystalline ribonuclease is reported. Studies on the effect of time of standing on the amount of inactivation, and on the effect of dilution and repeated high speed centrifugation on the recovery of virus activity, and the preparation of an insoluble virus-enzyme complex show that the inactivation is brought about at least in part by a comb...

1. Partially purified preparations of rat brain 4-aminobutyrate aminotransferase were inhibited in a time-dependent manner by ethanolamine O-sulphate. The inhibition was not reversed by dialysis. 2. The inhibitor formed an initial reversible complex with the enzyme (K(i)=4.4x10(-4)m) and the rate of inactivation followed pseudo-first-order kinetics (k=7.15x10(-4)s(-1)). The inclusion of 4-amino...

A reversible effect of pH on the ionization of amino-acid residues at the active center of choline oxidase was observed near the optimum pH (8). Inactivation of choline oxidase took place in the pH ranges 3-6 and 9-11, in which irreversible changes in the structure occur leading to the enzyme inactivation. The first order rate constants of the enzyme's inactivation at various pH values were est...