Translocators

The principles and details of enzyme assays are discussed in Bergmeyer (1983) and Suelter (1990). The object of this chapter is thus not proteins that change molecules (enzymes) but proteins that control the spatial distribution of molecules or ions transporters and ion channels. Transporters and ion channels are also called translocators. 

Transporters mediate the admission or delivery of lipid-unsoluble materials (sugars, amino acids, ions) via the phospholipid membranes of the cell. Transporters do not have a porous structure, Wt transport their freight in three steps binding of the substrate to one side of the membrane, conformation change or position change of the transporter-substrate complex, and dissociation of the substrate from the transporter on the other side of the membrane. Often, not only one molecule is being transported but several at the same time, either in the same direction (symport e.g., and lactose) or in opposite direction (antiport e.g., Na versus Ca ). Primary active transport processes (pumps) are powered by ATPases (e.g., Na / 

ATPase), while secondary active transport processes are coupled to H+ or Na gradients or to the membrane potential. 

The currently known transporter proteins have up to a dozen transmembrane helixes, some of which are amphipatic and the rest hydrophobic. The amphipatic helixes of the transporter presumably form an inner circle that is held together by an outer circle of hydrophobic helixes in the membrane. 

Transporters have binding sites for their substrate. Transport processes, just like the kinetic quantities of transport speed and exchange rate, are characterized by the affinity of the substrate to the transporter protein and the number of its binding sites. The transport speed (e.g., in rM substrate/min) reaches a maximum value with increasing substrate concentration, the maximum transport speed (Vmax). The exchange rate (in sec ) measures the number of substrate molecules transported by a transporter molecule per second. 

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C2H4N4. A translocated herbicide, m.p. 157-159 C, used as a non-selective herbicide on fallow land or in established orchards. 

MCPB, 4-(4-chloro-2-methylphenoxy)-butyric acid, CiiHisClOj. A compound in itself harmless to plants, but when absorbed and translocated in the cells, CnHuClOs is converted to a powerful herbicide, and results in the death of the plant. Acts as a selective weedkiller. Other butyric acid derivatives used commercially are 2,4-Dg and 2,4,5-Tb, the butyric acid analogues of 2,4-D and 2,4,5-T. ... 

CaH24N.,03P2,(Me2N)2P(0)0P(0)(NMe2)z. It is not highly toxic to insects when used as a contact insecticide, but is readily absorbed by the roots and leaves of plants and translocated in the sap, so that the plant becomes toxic to species feeding on it. 

The concentration of alkaloids, as well as the specific area of occurrence or localization within the plant or animal, can vary enormously. Thus the amount of nicotine [54-11-5] (21), C2QH24N2, apparentiy synthesized ia the roots of various species of JSHcotiana and subsequentiy translocated to the leaves varies with soil conditions, moisture, extent of cultivation, season of harvest, etc and may be as high as 8% of the dry leaf, whereas the amount of morphine (2, R = H) ia cerebrospiaal duid is of the order of 2 to 339 fmol/mL (23). 

On ornamental plants CCC is appHed to a2aleas, geraniums, and hibiscus (Hibiscus sp] to make compact plants, and to poinsettias to reduce stem height and increase the red color of the bracts. A considerable amount of work has been carried out on cereals with CCC to reduce stem length and inhibit lodging. In Europe, the effect of CCC on shortening the culms of cereals is dependent upon the genotype. It has been demonstrated that the effect is as follows wheat > triticale > durum wheat > rye > oats > barley > corn = millet = rice (37). In barley, culms are initially inhibited but later the plant overcomes the inhibition (37). This has been attributed to poor assimilation, translocation, and rapid breakdown in wheat (38). 

Inabenfide. [4-Chloro-2-(a-hydroxybenzyl)]-isonicotonanilide) [82211 -24-3] (Inabenfide) (32) is not for use in the United States, but is used in other countries to inhibit the growth of rice plants. The compound is appHed to the soil 40—60 days prior to the heading up of plants, where it is absorbed through the roots and translocated throughout the stem. It inhibits the elongation of the lower intemodes and this stops lodging. It is extremely toxic to fish. 

Biorational approaches have proven useful in the development of classes of herbicides which inhibit essential metaboHc pathways common to all plants and thus are specific to plants and have low toxicity to mammalian species. Biorational herbicide development remains a high risk endeavor since promising high activities observed in the laboratory may be nullified by factors such as limitations in plant uptake and translocation, and the instabiHty or inactivity of biochemical en2yme inhibitors under the harsher environmental conditions in the field. Despite these recogni2ed drawbacks, biorational design of herbicides has shown sufficient potential to make the study of herbicide modes of action an important and growing research area. 

In this type of activation, which occurs in both animal and plant tissues, the original insecticide is relatively stable and can be translocated through plant tissues without destmctive hydrolysis until the oxidation has occurred, which then makes the insecticide both highly toxic and relatively unstable so that it rapidly is hydroly2ed to nontoxic products. 

Genetic Control. Manipulation of the mechanisms of inheritance of the insect pest populations has occurred most successhiUy through the mass release of steri1i2ed males, but a variety of other techniques have been studied, including the environmental use of chemostetilants and the mass introduction of deleterious mutations, eg, conditional lethals and chromosomal translocations (58 ndash 60) (see Genetic engineering). 

Metabolic Functions. Chromium (ITT) potentiates the action of insulin and may be considered a cofactor for insulin (137,138). In in vitro tests of epididymal fat tissue of chromium-deficient rats, Cr(III) increases the uptake of glucose only in the presence of insulin (137). The interaction of Cr(III) and insulin also is demonstrated by experimental results indicating an effect of Cr(III) in translocation of sugars into ceUs at the first step of sugar metaboHsm. Chromium is thought to form a complex with insulin and insulin receptors (136). 

Excitation of smooth muscle via alpha-1 receptors (eg, in the utems, vascular smooth muscle) is accompanied by an increase in intraceUular-free calcium, possibly by stimulation of phosphoUpase C which accelerates the breakdown of polyphosphoinositides to form the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 releases intracellular calcium, and DAG, by activation of protein kinase C, may also contribute to signal transduction. In addition, it is also thought that alpha-1 adrenergic receptors may be coupled to another second messenger, a pertussis toxin-sensitive G-protein that mediates the translocation of extracellular calcium. 

Ethylene oxide has been shown to produce mutagenic and cytogenic effects in a variety of test systems (226). An increased frequency of chromosomal aberrations in peripheral lymphocytes of monkey exposed to ethylene oxide for 104 weeks has been reported (240). In mice, it is an effective inducer of chromosome breaks leading to dominant-lethal mutations. In addition, ethylene oxide has been shown to induce heritable effects in the heritable translocation test conducted in mice exposed to ethylene oxide by inhalation (241,242). In this study, male mice were exposed to ethylene oxide ranging from 165 to 300 ppm for 6 h per day 5 or 7 days/week for 8.5 weeks. Ethylene oxide has also been shown to bind to proteins (243) as well as to DNA (244). Several studies on ethylene oxide-exposed workers have demonstrated an increased incidence of chromosomal aberrations and sister chromatid exchanges the relevance of such effects to human health evaluation is currendy uncertain. 

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