Execution Pathway

2e Execution Pathway. The extrinsic and intrinsic pathways both end at the point of the execution phase, considered the final pathway of apoptosis. It is the activation of the execution caspases that begins this phase of apoptosis. Execution caspases activate cytoplasmic endonuclease, which degrades nuclear material they also activate proteases, which degrade the nuclear and cytoskeletal proteins. Caspase 

TABLE 16.4. Intrinsic Pathway Proteins, Abbreviations, and Alternate Nomenclature 

Abbreviation Protein Name Select Alternate Nomenclature 

Smac/DIABLO Second mitochondrial activator of caspases/direct IAP-binding protein with low PI None 

HtrA2/Omi High-temperature requirement Omi stress regulated endoprotease, serine protease Omi protein A2 

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TABLE 16.5. Execution Pathway Proteins, Abbreviations and Alternate Nomenclature... 

Because of its motor, i.e., activating effect on vascular smooth muscle and its inhibitory effect on intestinal smooth muscle, the sympathetic nervous system has been cast into the role of the component of the nervous system that executes control of visceral function in times of physical emergency for the organism. The phrase fight or flight has been often used to describe the circumstances in which the adrenergic transmitters of the sympathetic system are dominant over the cholinergic parasympathetic system. This concept is perhaps oversimplified but it has the utility of a first approximation of how the two components of the ANS interact in the periphery. Sensory inputs which lead to increased blood pressure, for example, activate the sympathetic pathways. 

The central dogma of apoptosis is that all the initiating pro-apoptotic stimuli converge on the mitochondrial compartment. Thus, although apoptosis can be initiated elsewhere, the execution phase of apoptosis induced by ionizing radiation needs mitochondria. How do DNA lesions trigger mitochondria Several metabolic pathways coimect mitochondria to the nucleus. 

Stopped-flow experiments, illustrated by pathway A of Figure 7.8, are better suited for sample components present at low concentrations since a separated analyte can be selected and held in the NMR probe allowing extensive signal averaging. Execution of stopped-flow acquisition requires calibration of the exact length of time it takes... 

Once the "synthesis tree" has been elaborated, we must proceed to the evaluation of the alternative pathways and compare them with possible synthetic schemes in order to optimise the chosen route and make it as self-consistent as possible. However, all synthetic plans must be flexible enough to allow new alternative solutions when things do not happen as anticipated. In this sense. Woodward referred very often to opportunism and of taking advantage of the "surprises" which may occur during the execution of a synthesis. Through the different stages of a synthesis new aspects may evolve and even important discoveries may be made. Such was the case, for instance, in the vitamin B12 synthesis in which the considerations of the stereochemistry of an intermediate, opposite to the one anticipated, led Woodward to the discovery of the principle of conservation of orbital symmetry [29]. 

The PFC, PAC, and ITC all project to the caudate nucleus as part of the cognitive circuit through the basal ganglia, which projects via the thalamus back to PFC (Fig. 8.2). In contrast, the motor circuit involves cortical projections to the putamen, which in turn projects back onto the premotor cortices (Fig. 8.2). This pathway is important for the planning, selection, initiation, and execution of movements. The entire cortical mantle also projects indirectly to the cerebellar cortex (not shown), which ultimately projects back to the primary motor cortex. This pathway serves as a biological gyroscope, providing on-line correction of movements. 

The execution of the apoptotic program is strictly controlled at several levels. This creates links to signaling pathways that have a control function in cell division. 

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