Some Biochemical Generalizations

Post-translational modifications were recognized as additional sources of the structural modification of proteins.(22) Should such a modification occur by an enzyme-mediated process, as had been established for oxidation of sulfhydryl groups or the addition of carbohydrate or phosphate groups, or by the cleavage of the polypeptide with loss of a terminal amino group, or a larger part of the chain, it too could be subject to genetic variation. 

The VNTRs or minisatellites of the human genome may be repeated 100 times or more in different persons. Many VNTRs, numbering in the thousands, are well characterized. Restriction fragment analysis will produce different size fragments proportional to the number of repeats in the VNTR. Where the identification of traits has been slowed for lack of a sufficient number of suitable genetic markers, the use of VNTRs should alleviate this constraint.(24) 

For the reasons stated above, pharmacogenetic polymorphisms must be defined on phenotypic grounds. Any comprehensive description of a given pharmacogenetic polymorphism should include information about the phenotype that characterizes the polymorphism and the genotype(s) that explain the polymorphism. 

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Reviews on the microbial metabolism of hydrocarbons with biochemical aspects are available, and inclnde those of Britton (1984) on alkanes, and of Morgan and Watkinson (1994) that also includes cycloalkanes and some aromatic compounds. Virtually all the issues that are discussed in these recur in the examples that are used as illustration. Some broad generalizations are summarized ... 

We have already dealt with some general aspects of biochemical self-assembly in Section 2.10 including the remarkable formation of viral capsids. There are some biochemical examples, however, that translate readily into supramolecular chemical concepts and have been pivotal in defining the field. One such system is the tobacco mosaic virus, a virus that is very harmful to a variety of crops including tobacco, tomato, pepper, cucumbers and species such as ornamental flowers. This system consists of a helical virus particle measuring some 300 X 18 nm (Figure 10.6). A central strand of RNA is sheathed by 2130 identical protein subunits, each of which contains 158 amino acids. What is remarkable about... 

Biological processes at the level of the single cell or at the level of the more complex, multicellular forms of life constitute some of the most intricate and challenging problems of chemistry and chemical kinetics. From the enormous amount of work that has been done on elucidating the elementary kinetic pathways in biological processes, some few generalizations can be made. One of these is that most discrete structural steps in biochemical processes are catalyzed by large molecules called enzymes. 

Spectroscopic methods are facile, convenient and noninvasive techniques for the identification of chemical compounds. The techniques generally require a small quantity of samples and are particularly suitable for the identification of biomolecules. For this purpose, it is required that the spectra of the biomolecules or related structures of the interested compounds are known. Spectral Database System (SDBS) maintained spectra of many organic compounds, including some biochemical compounds that can be searched and retrieved at http //www.aist.go.jp/RIODB/SDBS/menu-e.html as illustrated in Figure 2.1. 

Nonliquefied compressed gases are of no use for pMDIs because liquid is needed for suspension of the dmg and the addition of water makes propulsion of the aerosol in an appropriate manner technically impossible. Hydrocarbons in general have the wrong density for use as propellants in pMDIs. While snitable as propellants for some nonmedicinal honsehold purposes, they are difhcult to use in a situation where dose reprodncibility is essential, and most are of course flammable and thus inappropriate for inhalation. The HCFCs are ozone-damaging and additionally have adverse toxicological effects on the heart and some biochemical hepatic functions. 

The five organ functions assessed in safety pharmacology are the cardiovascular system, nervous system, respiratory system, gastrointestinal system and renal system. To these we would add general systemic metabolic functions, as these are amenable to collectiOTi of at least some biochemical and physiological data. 

Reviews conferences, symposia - There are some general reviews of current therapy as well as a discussion of some biochemical effects of anthelminthic drugs . Individual drugs considered at specific meetings were niridazole and thiabendazole . 

As with all antiarthritic drugs, the situation is not clear. Biochemical effects of copper are general, and no one target, such as a particular protein, is recognizable. The copper complexes are presumably a means of further increasing the copper content, because the species are expected to be rather labile. The introduction of exogenous copper will also affect thiol content and redox state of the cell, and some biochemical responses listed above may be a consequence of this altered state. Besides ceruloplasmin and albumin, major binding sites of Cu(II) are histidine and cysteine [94, 95] and some possibilities for the mechanism of action have been summarized [64]. 

Parkinson s disease is the brain disease in which clearest evidence has been obtained that a disturbance of brain amine metabolism plays a major role in the development of symptoms. It is also a striking example of a common brain disease of which a knowledge of the biochemical disturbance has led to the prediction of a successful rational therapy. Some useful general accounts of developments in this area have recently appeared [107, 108, 109],... 

The examples discussed illustrate that assignment of the resonances is usually relatively straightforward. This combined with the 100% natural abundance of the nucleus may explain the popularity of the P-NMR technique for the study of phosphoproteins. The sensitivity is about 5% of H-NMR sensitivity. For most other nuclei, this disadvant e can be overcome by the use of higher magnetic fields. However, as discussed for the study of phosphoproteins, contributions of the chemical-shift anisotropy relaxation mechanism often prohibit advantageous appUcation of such instruments, much as was observed for the F nucleus (Sykes and Weiner, 1980). Table IV presents an overview of the majority of P-NMR studies presented in this chapter. Some biochemically interesting generalizations can be made on the basis of these results and are discussed further. 

There has been a surge of research activity in the physical chemistry of membranes, bilayers, and vesicles. In addition to the fundamental interest in cell membranes and phospholipid bilayers, there is tremendous motivation for the design of supported membrane biosensors for medical and pharmaceutical applications (see the recent review by Sackmann [64]). This subject, in particular its biochemical aspects, is too vast for full development here we will only briefly discuss some of the more physical aspects of these systems. The reader is referred to the general references and some additional reviews [65-69]. 

The Henderson-Hasselbalch equation provides a general solution to the quantitative treatment of acid-base equilibria in biological systems. Table 2.4 gives the acid dissociation constants and values for some weak electrolytes of biochemical interest. 

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