Eliminating organs, protein metabolism

Figure 5.3. A binding curve is simply a dose-response curve determined at the biomolecular level. In contrast to the dose-response curve determined on a whole organism, it is easier to ensure that the substance has good access to the protein, metabolism can be eliminated and the full range of a response will be available. In this graph, the binding curves of two different substances capable of binding to the same protein are shown. Substance A occupies 50% of the binding sites at one-tenth the concentration needed to bring about the same degree of occupancy with Substance B.

Protein Metabolism in Eliminating Organs. Peptidases in the gastrointestinal... 

Proteolytic enzymes such as proteases and peptidases are ubiquitous throughout the body. Sites capable of extensive peptide and protein metabolism are not only limited to the liver, kidneys, and gastrointestinal tissue, but also include the blood and vascular endothelium as well as other organs and tissues. As proteases and peptidases are also located within cells, intracellular uptake is per se more an elimination rather than a distribution process [13]. While peptidases and proteases in the gastrointestinal tract and in lysosomes are relatively unspecific, soluble peptidases in the interstitial space and exopeptidases on the cell surface have a higher selectivity and determine the specific metabolism pattern of an organ. The proteolytic activity of subcutaneous tissue, for example, results in a partial loss of activity of SC compared to IV administered interferon-y. 

A 6 month inhalation study was conducted in rats in which the animals were exposed daily to 10 mg m At 3 months, neuromuscular depression, lymphopenia, neutrophilia, and decreased oxygen consumption were observed. In the fifth month, increased organic sulfate elimination, variation in weight, arterial pressure, liver function, and protein metabolism were observed. Liver damage was reported upon histological examination. Studies on the teratogenic, embryotoxic, and cytogenic effects of 2-ME have been inconclusive. 

The tasks of the liver are manifold ranging from bile production, storage of carbohydrates, synthesis of plasma proteins, phase 1 and phase II metabolism, to formation of urea. It is the central organ of metabolism and elimination for a large variety of endobiotics and xenobiotics, and correspondingly hepatocytes express a multitude of transport proteins in their sinusoidal (basolateral) and canalicular plasma membrane (Figure 9.9). 

Pyrethroids bind strongly to plasma proteins before being distributed by the blood to the organs for metabolism and elimination. Only the unbound or free pyrethroids contribute to toxicity and are susceptible to metabolic reactions. Pyrethroids that have a high binding constant for a plasma protein show lower toxicity and... 

Chemical properties appropriate to a compound found at a branch point of metabolism are displayed by chorismic acid. Simply warming the compound in acidic aqueous solution yields a mixture of prephen-ate and para-hydroxybenzoate (corresponding to reactions h and l of Fig. 25-1). Note that the latter reaction is a simple elimination of the enolate anion of pyruvate. As indicated in Fig. 25-1, these reactions correspond to only two of several metabolic reactions of the chorismate ion. In E. coli the formation of phe-nylpyruvate (steps h and i, Fig. 25-1) is catalyzed by a single protein molecule with two distinctly different enzymatic activities chorismate mutase and prephenate dehydratase.34-36 However, in some organisms the enzymes are separate.37 Both of the reactions catalyzed by these enzymes also occur spontaneously upon warming chorismic acid in acidic solution. The chorismate mutase reaction, which is unique in its mechanism,373 is discussed in Box 9-E. Stereochemical studies indicate that the formation of phenylpyruvate in Fig. 25-1, step z, occurs via a... 

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