Biochemical sites

This degree of lowering of brain inositol would not appear to be sufficiently near the Km of PI synthase to slow PI synthesis. It has also been observed that Li+ must be administered for many days before a therapeutic effect is seen. This suggests that delayed effects of Li+, such as regulation of enzymes, might better correlate with the clinical effect. While the inositol depletion hypothesis appears attractive in many respects, its validity remains to be demonstrated. A number of other biochemical sites of Li+ action have been reported [3,4], and it maybe that multiple actions of Li+ are necessary for its clinical effectiveness. 

Biochemical site of action Site 1 on voltage-dependent sodium channel Site 5 on voltage-dependent sodium channel Catalytic subunit of phosphorylase phosphatases Kainate receptor in central nervous system Unknown Ciguatoxin site 5 on voltage-dependent sodium channel Maitotoxin calcium channels... 

According to McFarland [26], aquatic toxicity can be considered the result of penetration of toxicant into biophases and its interaction with one or more biochemical sites of action. Thus, he and others have postulated that toxicity is a function of the ability of the chemical to enter biophases and its ability to react with cellular compounds. Bioavailability of chemicals in fish has been shown to be related to chemical flux across fish gills [27], an identified exposure pathway. Flux across fish gills is in turn related to the ability of the chemical to partition between organic and aqueous phases, which is usually correlated with the its octanol-water partition coefficient (logPo/w) [28]. It is therefore not surprising that the acute toxicity of narcotic chemicals has been shown to be related to their propensity to accumulate in the membranes, and hence their logPe/w [29]. 

Biochemical, Site-Specific Incorporation of A -(5-Azido-2-nitrobenzoyl)lysine into Proteins... 

Biochemical, Site-Specific Incorporation of 4- 3-(Trifluoromethyl)-3//-diazirin-3-yl]phenylaIanine into Proteins by Phe(4-Tmd)-tRNAPhe... 

As indicated at the outset of this broad-based review, although of the order of ten thousand plant defensive compounds have been isolated and structurally characterized, only of the order of a thousand have so far been shown to interact with specific proteins and most of these biochemical sites of interaction are signal transduction components. The elucidation of such targets now permits rapid biochemical screening of complex ecosystems for plant-derived ligands for such proteins. 

Milbemectin is a GABA agonist. Therefore, for those acaricides that also possess high insecticidal activity, they share the same modes of action as found in insects. Table 7.2 summarizes the biochemical sites of action of insecticides and acaricides. 

Table 7.2 Biochemical sites of action of insecticides and acaricides...

Ishaaya, I., Biochemical sites of insecticide action and resistance, Ishaaya, I., Ed., Berlin Springer-Verlag, 2001.. 

Gunning, R.V. and Moores, G.D., Insensitive acetylcholinesterase as sites for resistance to organo-phosphates and carbamates in insects insensitive acetylcholinesterase confers resistance in Lepidoptera, in Biochemical sites of insecticide action and resistance, Ishaaya, I., Ed., Berlin Springer-Verlag, 2001, p. 221. 

R. Nauen, U. Ebbinghaus-Kintscher, A. Elbert, P. Jeschke and K. Tietjen in Biochemical Sites of Insecticide Action and Resistance (Ed. I. Ishaaya), Springer, Tokyo, 2000, h>. 77-105. 

The exclusion of selenium from the proteins of accumulator plants is thought to be the basis for their selenium tolerance. Their selenium metabolism is based mainly on water-soluble nonprotein forms such as selenium methylselenomethionine (Jacobs, 1989). The garlic odor characteristic of selenium-accumulator plants reflects the volatile organic compounds dimethylselenide and dime-thyldiselenide. Plants can suffer selenium toxicity as a result of selenium competition with essential metabolites for biochemical sites, replacement of essential ions by selenium, mainly major cations, selenate occupation of the sites of essential groups such as phosphate and nitrate, or selenium substimtion in essential sulfur compounds. 

Choosing drugs which act at different biochemical sites in the cell... 

The outlier interacts by a different molecular mechanism at its biochemical site of action than the other studied chemicals. 

Some of the above biochemical pathways are found exclusively in the helminths and offer unique targets for chemotherapeutic attack. This subject has been reviewed by several workers [4-12]. The present chapter will highlight only the vulnerable biochemical sites of helminths for chemotherapeutic attack and effective drug design. 

Hemrich. R.. Melendez-Hevia, E., Montero, F., Nuno, J. C..Sicphani, A., and Waddell. T. G. 1999. TTie structural design of glycolysis An evolutionary approadi. Biochem. Site. Trans. 27 294-298. 

Biochemical site of action of erythromycin Inhibits bacterial protein biosynthesis at the translocation step of translation... 

The biochemical site of action of EPTC, as is the case with the other thiocarbamates, is not exactly known. 

The heart poisons or cardiotoxins are, in reality, general muscle poisons. However their effect on the muscle of the heart is by far the most important in terms of killing the snake s prey or attacker. These incredibly potent toxins bind to specific biochemical sites on the surface of muscle cells causing depolarisation. The muscle cell works in a manner akin to neurones in that it transmits information, to initiate a contraction, by exchanging + and - ions across its cell... 

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