Pathways central

Bollrath J, Greten FR (2009) IKK/NF-kappaB and STAT3 pathways central signalling hubs in inflammation-mediated tumour promotion and metastasis. EMBO Rep 10(12)4314-1319. doi 10.1038/embor.2009.243... 

Fig. 14.16 Schematic overview of the Wnt signaling pathway. Central to wnt signaling is a protein complex composed of/ -catenin, APC, glycogen synthase kinase 3 (CSK3) and axin.

In pain pathways, central sensitization involves enhanced efficiency of excitatory synaptic transmission pathways within the CNS, notably in the dorsal horn of the spinal cord at the synapse between the sensory nociceptor fibres and second-order relay neurones (Ji et al. 2003). It has been suggested that central sensitization in the cough reflex loop might also underlie hypertussive states (Bonham et al. 2004, 2006a, b), but to date, there are few data confirming this. 

This is not the place to expose in detail the problems and the solutions already obtained in studying biochemical reaction networks. However, because of the importance of this problem and the great recent interest in understanding metabolic networks, we hope to throw a little light on this area. Figure 10.3-23 shows a model for the metabolic pathways involved in the central carbon metabolism of Escherichia coli through glycolysis and the pentose phosphate pathway [22]. 

Modulation of second-messenger pathways is also an attractive target upon which to base novel antidepressants. Rolipram [61413-54-5] an antidepressant in the preregistration phase, enhances the effects of noradrenaline though selective inhibition of central phosphodiesterase, an enzyme which degrades cycHc adenosiae monophosphate (cAMP). Modulation of the phosphatidyl iaositol second-messenger system coupled to, for example, 5-HT,, 5-HT,3, or 5-HT2( receptors might also lead to novel antidepressants, as well as to alternatives to lithium for treatment of mania. Novel compounds such as inhibitors of A-adenosyl-methionine or central catechol-0-methyltransferase also warrant attention. 

Two groups of substituted l,4-ben2oquiaones are associated with photosynthetic and respiratory pathways the plastoquinones, eg, plastoquinone [4299-57-4] (34), and the ubiquinones, eg, ubiquinone [1339-63-5] (35), are involved in these processes. Although they are found in all living tissue and are central to life itself, a vast amount remains to be learned about their biological roles. 

The distribution of rods and cones is shown in Figure 3b centered about the fovea, the area of the retina that has the highest concentration of cones with essentially no rods and also has the best resolving capabiUty, with a resolution about one minute of arc. The fovea is nominally taken as a 5° zone, with its central 1° zone designated the foveola. There are about 40 R and 20 G cones for each B cone in the eye as a whole, whereas in the fovea there are almost no B cones. A result of this is that color perception depends on the angle of the cone of light received by the eye. The extremely complex chemistry involved in the stimulation of opsin molecules, such as the rhodopsin of the rods, and the neural connections in the retinal pathway are well covered in Reference 21. 

The chromaffin cells of the adrenal medulla may be considered to be modified sympathetic neurons that are able to synthesize E from NE by /V-methylation. In this case the amine is Hberated into the circulation, where it exerts effects similar to those of NE in addition, E exhibits effects different from those of NE, such as relaxation of lung muscle (hence its use in asthma). Small amounts of E are also found in the central nervous system, particularly in the brain stem where it may be involved in blood pressure regulation. DA, the precursor of NE, has biological activity in peripheral tissues such as the kidney, and serves as a neurotransmitter in several important pathways in the brain (1,2). 

FIGURE 18.2 The metabolic map as a set of dots and lines. The heavy dots and lines trace the central energy-releasing pathways known as glycolysis and the citric acid cycle. 

Although most cells have the same basic set of central metabolic pathways, different cells (and, by extension, different organisms) are characterized by the alternative pathways they might express. These pathways offer a wide diversity... 

Certain of the central pathways of intermediary metabolism, such as the citric acid cycle, and many metabolites of other pathways have dual purposes—they serve in both catabolism and anabolism. This dual nature is reflected in the designation of such pathways as amphibolic rather than solely catabolic or anabolic. In any event, in contrast to catabolism—which converges to the common intermediate, acetyl-CoA—the pathways of anabolism diverge from a small group of simple metabolic intermediates to yield a spectacular variety of cellular constituents. 

Carboxylic acids, RC02H, occupy a central place among carbonyl compounds. Not only are they valuable in themselves, they also serve as starting materials for preparing numerous acyl derivatives such as acid chlorides, esters, amides, and thioesters. In addition, carboxylic acids are present in the majority of biological pathways. We ll look both at acids and at their close relatives, nitriles (RC=N), in this chapter and at acyl derivatives in the next chapter. 

A variety of starting materials other than glucose or its derivatives is possible for use by some micro-organisms the four shown in Figure 5.1 are all initially converted to acetyl CoA for entry into the central metabolic pathways. 

Many anticancer agents currently in use, including chemotherapeutic drugs and radiation, are potent inducers of apoptosis and cell-cycle arrest. It is believed that induction of these molecular pathways is central to the efficacy of such agents [1]. Genetic and epigenetic alterations that contribute to tumorigenesis... 

Alterations to the P53 gene are the most common genetic defects known in cancer [5]. The protein product of P53 is involved in a number of pathways that directly and indirectly lead to apoptosis. Many genes that are involved in apoptosis can be induced by this protein, which is a transcriptional transactivator. The emerging hypothesis is that p53 is a central node of a complex apoptotic network that may function differ ently in diver se cell types and tissues. For example, Bax, the prototype proapoptotic member of the Bcl2 family, can be transcriptionally induced by p53 in certain, but not all, cell types. Like p53, Bax can modulate the extent to which cells are sensitive to apoptosis caused by therapeutic agents. 

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