Kinetics, inactivation

The 3 subunits ((31 -(34) are membrane proteins with a single transmembrane domain and an extracellular immunoglobulin-like motif, and perform the regulatory roles of the sodium channel. The (31 subunit accelerates the activation and inactivation kinetics. The (32 subunit is covalently linked to the a subunit, and is necessary for the efficient assembly of the channel. The more recently identified (33 subunit is homologous to (31, but differs in its distribution within the brain and in a weaker accelerating property. The (34 subunit is similar to (32 and is covalently linked to the a subunit. 

Complex inactivation kinetics caused by enzyme-catalyzed decomposition of epoxide kinetic constants calculated from initial rates of inactivation. Approximate value calculated from half-life in the presence of 50 mAf inhibitor. 

In experiments using oxidant stress induced by the photoactivation of rose bengal (10 nM), a 75% decline in the calcium inward current was observed after 10 min, with only a sUght acceleration in the inactivation kinetics of the current (Shattock etal., 1990). However, this decline in the calcium inward current appears to occur secondary to an oxidant stress-induced calcium overload and not as... 

In addition to the TDI experiment, the partition ratio measures the TDI efficiency. Specifically, the partition ratio is the number of inactivation kinetic events (k nact) versus the number of substrate turnover events per unit enzyme (kcat) [161], Thus, the most potent partition ratio is zero. The most common experimental setup for determining the partition ratio is the titration method that increases the inhibitor concentration relative to a known amount of enzyme. After the incubations, a secondary incubation containing a probe substrate similar to the TDI experiment is used to define the remaining activity. For accurate determination of the partition ratio from the titration method, it is assumed that the inhibitor is 100% metabolized ... 

A number of reports also describe the prediction of mechanism-based inhibition (MBI) [17,18]. In this type of model, MBI is determined in part by spectral shift and inactivation kinetics. Jones et al. applied computational pharmacophores, recursive partitioning and logistic regression in attempts to predict metabolic intermediate complex (MIC) formation from structural inputs [17]. The development of models that accurately predict MIC formation will provide another tool to help reduce the overall risk of DDI [19]. 

Prediction of DDI from in vitro inactivation data has also been accomplished. However, unlike the aforementioned simple cutoff that can be applied to inhibition data, no such simple cutoff criterion has been well established for mechanism-based inactivation kinetic parameters. Ratios of k act/kdeg and [ ] vivolKi have been shown to be related to the magnitude of DDI [50]. The early screens previously discussed rely upon abbreviated approaches to identify mechanism-based inactivation as an issue rather than provide quantitative data for predictions of DDI. 

Outward repolarizing currents oppose the effect of the inward Ica on the plateau phase. This current is carried predominantly through delayed rectifier potassium channels (Ik).These channels are voltage sensitive, with slow inactivation kinetics. Three distinct subpopulations of Ik with differing activation and inactivation kinetics have been described. A rapidly activating subset (Ikf), a slowly inactivating subset (Iks), and an ul-tra-rapidly activating subset to date are identified only in atrial tissue (Ikui)-... 

In order to describe and optimize the reverse micellar extraction process, Dekker et al. [ 170] have proposed a mathematical model, which satisfactorily describes the time dependency of the concentration of active enzyme in all the phases, based on the flow, mass transfer, and first-order inactivation kinetics. For each phase, a differential equation is derived. For forward extraction ... 

Arnold, W.N. (1969) Heat inactivation kinetics of yeast -fructofuranosidase. A poly disperse system. Biochim. Biophys. Acta, 178, 347-353. 

The inactivation kinetics of the Q-type channel are similar to the N-type channel but are resistant to DHPs and co-conotoxin GVIA. Q-type channels are inhibited by co-agatoxin IVA but less effectively than co-agatoxin IVA blocks P-type channels (review Miljanich and Ramachandran, 1995). 

TNP-amino acids 45). Various levels of TNBS were then reacted with the enzyme, and the inactivation kinetics were analyzed in terms of a multi-order reaction, according to the treatment of Levy et of. (47)... 

When the enzyme is inactivated by heating in the presence or absence of Mg2+, the inactivation kinetics of the three activities are indistinguishable (Fig. 7). 

Zook, C.D., Parish, M.E., Braddock, R.J. and Balaban, M.O. (1999) High pressure inactivation kinetics of Saccharomyces cerevisiae ascospores in orange and apple juices. Journal of Food Science 64(3), 533-5. 

Figure 13. Inactivation kinetics of allenic secosteroids [all secoste-...

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