Secondary compartmentalization

A problem with employment of ASON in a larger clinical setting is their poor uptake and inappropriate intracellular compartmentalization, e.g., sequestration in endosomal or lysosomal complexes. In addition, there is a need for a very careful selection of the ASON-mRNA pair sequences that would most efficiently hybridize. To date, several computer programs are used to predict the secondary and tertiary structures of the target mRNA and, in turn, which of the mRNA sequences are most accessible to the ASON. However, even with this sophisticated techniques, the choice of base-pairing partners still usually includes a component of empiricism. Despite these principal limitations, it has become clear that ASON can penetrate into cells and mediate their specific inhibitory effect of the protein synthesis in various circumstances. 

J. Guern, J. P. Renaudin, S. C. Brown, The compartmentation of secondary metabolites in plant cell cultures. Cell Culture and Somatic Cell Genetics of Plants. Vol. 4 (F, Constabel and 1. K. Vasil, eds.). Academic Press, San Diego, 1987, p. 43. A. L. Samuels, M. Fernando, and A. D. M. Glass, Immunofluorescent localization of plasma membrane H -ATPase in barley roots and effects of K nutrition. Plant Physiol. 99 1509 (1992). 

Wink M (1997) Compartmentation of secondary metabolites and xenobiotics in plant vacuoles. In Leigh RA, Sanders D, Callow JA (eds) The plant vacuole advances in botanical research, vol 25. Academic, London, pp 141-169... 

Keeping in mind all three DNA structure levels, primary, secondary, and tertiary, it is essential to understand that the lower level will mediate but not fully determine the higher structural level. In other words, the secondary as well as tertiary DNA structures of ODN in solution will be affected by many physical and chemical parameters, such as temperature, pH, salt content, compound concentration, etc. When evaluating complex biochemical systems, additional factors have to be taken into consideration possible interactions of ODN with a variety of other molecules and macromolecules in solution, local concentration effects and compartmentalization, biological half-life, etc. Hence when designing a DIMS ODN compound, its 3-D structure will not be fully predictable. 

It is generally accepted that chloroplasts possess an intact pathway of aromatic amino acid biosynthesis that is tightly regulated. In addition, the subcellular location of some aromatic-pathway isozymes has been shown to be in the cytosol, but whether an intact pathway exists in the cytosol has not yet been proven. The evidence bearing on aromatic amino acid compartmentation and regulation is reviewed, with particular emphasis given to the relationship between primary biosynthesis and secondary metabolism in the cytosol. 

Clark CG, Roger AJ (1995) Direct evidence for secondary loss of mitochondria in Entamoeba histolytica. Proc Natl Acad Sci USA 92 6518-6521 Clayton CE, Michels P (1996) Metabolic compartmentation in African trypanosomes. Parasitol Today 12 465-471... 

The primary analysis examined pharmacokinetic parameters calculated from plasma concentrations of CYS-conjugated XYZ1234 using non-compartmental techniques. The secondary analysis examined the pharmacokinetic parameters of unconjugated XYZ1234. 

The model independent pharmacokinetic characteristics for XYZ1234 following single dose administration of the different treatments were calculated using non-compartmental procedures. The following table gives the arithmetic means, standard deviations, and coefficients of variation as well as the medians and ranges of the primary pharmacokinetic measure AUCo-co, and of the secondary measures Cm, Cmax and MRT. 

The structure and function of this bacterial photosystem reveals important principles for the design of artificial photosystems. First, the sensitizer needs to be posi tioned close to secondary acceptors and donors which themselves are spatially iso lated from each other such that photoexcitation leads to rapid spatial separation of the electron hole pair. Second, compartmentalization of the photosynthetic assembly is likely to be necessary so as to prevent wasteful back reactions. For water splitting, a system in which H2 and O2 are generated in separate compartments would have both safety and efficiency advantages. 

The biosynthesis of SM exhibits a remarkable complexity. Enzymes are specific for each pathway and are highly regulated in terms of compartmentation, time and space. The same is true for fhe mechanisms of accumulation or the site and time of storage. In general, we find fhaf fissues and organs which are important for survival and multiplication, such as epidermal and bark tissues, flowers, fruits and seeds, have distinctive profiles of SM, and secondary compounds are stored in high amounts in them. As an example, the complex pattern of alkaloid synfhesis, transporf and sforage is illustrated in Fig. 1.7. 

Guern, J., Renaudin, J.P and Brown, S.C. (1987) The compartmentation of secondary metabolites in plant cell cultures, in Cell Culture and Somatic Cell Genetics (eds R Constabel and I. Vasil). Academic Press, New York, pp. 43-76. 

Plate 3 Compartmentation of biosynthesis and sequestration. Abbreviations SM, secondary metabolites GS-SM, conjugate of SM with glutathione NPAAs, non-protein amino acids ATP, adenosine triphosphate ADP, adenosine diphosphate mt, mitochondrium cp, chloroplast nc, nucleus 1, passive transport 2, free diffusion 3, H+/SM antiporter 4, ABC transporter for SM conjugated with glutathione 5, ABC transporter for free SM 6, H+-ATPase. (Fig. 1.4, p. 9)... 

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