Of molecular events

Atoms, ions, and molecules rearrange and recombine during chemical reactions. These processes usually do not occur all at once. Instead, each reaction consists of a sequence of molecular events called a reaction mechanism. 

Implicit in the use of the term sequence of molecular events is the idea that the chemical transformation that one observes in the laboratory is not the result of a single molecular process but is the end result of a number of such processes. If one considers reactions such as... 

The series of molecular events responsible for the uptake process constitutes the endocytic pathway, which enables cells to internalize macromolecules from the cell exterior, forming an endosome. The endosome is an intermediate organelle that serves as an essential component for many receptor-mediated signaling pathways and as a transport vector for eventual delivery to a specialized organelle known as the lysosome. Once in the lysosomal lumen, digestive enzymes provide essential metabolites from these macromolecules (i.e. free amino acids and lipids) directly to the cytosol for their use. 

Most protein serine-threonine kinases undergo autophosphorylation. The autophosphorylation of most protein kinases is associated with an increase in kinase activity [4, 10]. In some instances, such as with the RII subunit of PKA, autophosphorylation represents a positive feedback mechanism for kinase activation, in this case by enhancing the rate of dissociation of the RII and C subunits. In the case of CaMKII, autophosphorylation causes the catalytic activity of the enzyme to become independent of Ca2+ and calmodulin. This means that the enzyme, activated originally in response to elevated cellular Ca2+, remains active after Ca2+ concentrations have returned to baseline. By this mechanism, neurotransmitters that activate CaMKII can produce relatively long-lived alterations in neuronal function. In other instances, such as with the receptor-associated protein tyrosine kinases (discussed in Ch. 24), autophosphorylation is an obligatory step in the sequence of molecular events through which those kinases are activated and produce physiological effects. 

Thus far, our discussion of chemical kinetics has centered on reaction rates. We ve seen that the rate of a reaction usually depends on both reactant concentrations and the value of the rate constant. An equally important issue in chemical kinetics is the reaction mechanism, the sequence of molecular events, or reaction steps, that defines the pathway from reactants to products. Chemists want to know the sequence in which the various reaction steps take place so they can better control known reactions and predict new ones. 

Spectroscopic techniques, such as ultra-violet (9), Infrared (25), Nuclear Magnetic Resonance (24), and Fluorescence spectroscopies (5-8), constitute direct probes of specific events occurring at the molecular scale. When a quantitative interpretation is possible, spectroscopy provides very detailed microscopic information. Unfortunately however, the interpretation of spectra in terms of molecular events is often complex. Yet another approach that probes events at the molecular scale involves the use of tracers, such as chromophores (1-225). Again, the complexity of the tracer imposes limitations on the extent to which the data can be interpreted quantitatively. 

We suggest that the results of calculations described above for a small (Cm < 1 mol liter ) salt concentration give a correct qualitative picture and relevant time/space scales of molecular events. 

We propose that these arguments are consistent with, but do not corroborate, the hypothesis that the platinum drug enhances the antigenic character of the tumor cells, tipping the balance in favor of the host s immunologic intervention to destroy the cancer. The question then becomes, how does the platinum drug accomplish this . Now we return to the derepression story based on Reslova s work. In brief, Fig. 7 outlines one potential sequence of molecular events in a mammalian cell which could produce the desired result. 

Traditional molecular excitation and subsequent system evolution, discussed in Chapter 2, affords little opportunity for us to control the outcome of molecular events. According to perturbation theory, as developed in Section 2.3, the branching ratio (i.e the relative probability to populate different product charnels) at the end of the process depends entirely [see Eq. (2.77)] on the ratio between squares ( , n e d ,>[2/ ( , nr e d ) 2 of the purely material transition dipole matrix elements. Thus, the electric field profile does not appear in the branching ratio expression. Since the electric field profile of the pulse is the means by which one could hope to influence and possibly control the outcome of the event, it seems that there is no way that we can change the natural branching ratio [37, 38],... 

The mechanisms of apoptosis are highly complex and sophisticated, involving an energy-dependent cascade of molecular events (Figure 16.11). There are two main apoptotic pathways the extrinsic or death receptor pathway and the intrinsic or... 

---