Kidney chemical modification

Elimination Filtration and secretion in the kidneys chemical modification in the liver... 

Although the antibacterial spectmm is similar for many of the sulfas, chemical modifications of the parent molecule have produced compounds with a variety of absorption, metaboHsm, tissue distribution, and excretion characteristics. Administration is typically oral or by injection. When absorbed, they tend to distribute widely in the body, be metabolized by the Hver, and excreted in the urine. Toxic reactions or untoward side effects have been characterized as blood dyscrasias crystal deposition in the kidneys, especially with insufficient urinary output and allergic sensitization. Selection of organisms resistant to the sulfonamides has been observed, but has not been correlated with cross-resistance to other antibiotic families (see Antibacterial AGENTS, synthetic-sulfonamides). 

The elimination of a drug is its removal from the body, either by chemical modification through metabolism or by removal from the body through the kidney, the gut, the lungs or the skin. 

In spite of the improved stability to nucleases, achieved through chemical modification, AS-ODN degradation in plasma still occurs, predominantly from the 3 -terminus. In the liver and kidney, the major sites of metabolism, AS-ODNs are degraded from the 5 -terminus as well [127,128]. 

As an example of how the chemical modification can influence the affinity of sulfonamides to certain tissues, the results of another model experiment are briefly reviewed. Groups of four rabbits received a single oral dose of 500 mg. per kg. of five different sulfonamides and were sacrificed 3 hours later. Free and total sulfonamide were determined in the cortex and medulla of the kidneys as well as in the blood plasma. A summary of the results limited to the free sulfonamide is presented in Figure 9. The most pronounced differences are seen between sulfisoxazole and sulfamethoxazole, two agents which are chemically similar. With sulfisoxazole, the kidney levels are much higher than the plasma levels and the sulfonamide content in the medulla of the kidney markedly surpasses the one in the cortex (index medulla/cortex = 1.6). With sulfamethoxazole, almost identical sulfonamide levels are found in kidney cortex, medulla, and blood plasma. 

Bjamason and Carpenter (38, 52, 53) studied the use of formylation, acetylation, and propionylation for blocking amino groups in food proteins. Many of these chemical modifications could be easily applied on a commercial scale. The formyl and acetyl derivatives were nutritionally utilized at least partially. The propionylated lysine was not utilized however the propionylated lactalbumin was partially utilized (Table VII). The acylation procedure lowered considerably the extent of the Maillard reaction. Previous investigations, in support of the observations of Bjamason and Carpenter, have shown deacylase in the kidney (51). 

Compounds that cannot be oxidized as fuels in the human are often excreted in the urine. Chemical modifications often occur in the liver, kidney, or other tissues that inactivate or detoxify the chemicals, make them more water-soluble, or otherwise target such molecules for excretion. Uric acid, the basis of Lotta Topaigne s pain, is excreted in the urine (see Fig. 5.26). Judging from the similarity in structure, do you think it is derived from the degradation of purines, pyrimidines, or pyridines ... 

The red kidney bean a-amylase inhibitor contains 9-10% covalently bound carbohydrate. Removal of up to 70% of the carbohydrate does not affect the activity of the inhibitor (110). The glyco groups, removed from the protein, do not inhibit a-amylase at 3.5 X 10 times the concentration of the inhibitor (110). Chemical modification studies indicate that histidine and tyrosine residues in the inhibitor may be important for its activity (110). 

Liver degrades 15%, whereas 10% are broken down in kidneys and another 10% are transferred through the stomach to the gastrointestinal tract, releasing amino adds and peptides that are reabsorbed and provide nutrition to the peripheral tissues [430]. The degradation mechanism involves fusion with lysosomes in the receptors of the endothelial cell surface and can be hindered by chemical modification of the albiunin [431]. 

In the balance of this paper, we describe the application of our method of chemical modification to the generation of fluorohydrolases The most common substrate to measure fluorohydrolase activity is diiso-propylphosphorofluoridate (DFP). Although DFP is not found in nature, Mazur reported the enzymatic hydrolysis of this highly toxic organo-fluorophosphate by an enzyme isolated from hog kidney.Since then, diisopropyl phosphorofluoridate fluorohydrolase (DFPase, E.C. 3.8.2.1) has been extensively studied and well characterized. In addition, enzymes with organofluorophosphate hydrolyzing activity have been shown to be widely distributed phylogenetically and sources are known from bacteria, protozoa, invertebrates, and vertebrates. 

One class of mechanism-based MAO inhibitors includes the unsaturated alkylamines (propargylamine analogs) (Table II). Although the kinetics of enzyme inactivation for these compounds are consistent with a mechanism-based inhibitor, in only a few cases has the chemical mechanism and site of protein modification been determined. Pargyline (iV-benzyl-N-methyl-2-propynylamine) is a classic example. Pargyline reacts stoichiometrically and irreversibly with the MAO of bovine kidney, with protection from inactivation afforded by substrate benzylamine (91). Furthermore, the reaction involves bleaching of the FAD cofactor at 455 nm and the formation of a new absorbing species at 410 nm and a covalent adduct of inactivator with flavin cofactor (92). 

Some substances attack other organs specifically, aside from the liver and kidneys. Damage can be caused by the formation of specific donor-acceptor complexes at special receptors and by direct modifications of the cell. The target organs and specific damage caused by numerous chemicals are well known (see Table 2.1). 

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