Metabolism mechanisms

FIGURE 5.3 Different types of functional readouts of agonism. Receptors need not mediate cellular response but may demonstrate behaviors such as internalization into the cytoplasm of the cell (mechanism 1). Receptors can also interact with membrane proteins such as G-proteins (mechanism 2) and produce cytosolic messenger molecules (mechanism 3), which can go on to mediate gene expression (mechanism 4). Receptors can also mediate changes in cellular metabolism (mechanism 5). 

D7. Dietrich, L. S., Friedland, I. M., and Kaplan, L. A., Pyridine nucleotide metabolism mechanism of action of the niacin antagonist, 6-amino-nicotinamide. ]. Biol. Chem. 233, 964-968 (1958). 

Plunkett W, Huang P, Xu YZ, Heinemann V, Grunewald R, Gandhi V. Gemcitabine metabolism, mechanisms of action, and self-potentiation. Semin Oncol 1995 22(4 Suppl 11) 3—10. 

The results of these studies implicate dysfunctions in presynaptic storage, release, reuptake, and metabolic mechanisms in dopamine mesolimbic systems (Davis and Lieberman, 2000). 

Ammonia is produced by all tissues during the metabolism of a variety of compounds, and it is disposed of primarily by formation of urea in he liver. However, the level of ammonia in the blood must be kept very fcw, because even slightly elevated concentrations (hyperammonemia) ae toxic to the central nervous system (CNS). There must, therefore, be a metabolic mechanism by which nitrogen is moved from peripheral tissues to the liver for ultimate disposal as urea, while at the same hre low levels of circulating ammonia must be maintained. 

Metabolic mechanisms Varied, particularly that of Glycolysis is pathway for... 

Hurst, S., Loi, C. M., Brodfuehrer, J., and El-Kattan, A. (2007). Impact of physiological, physicochemical and biopharmaceutical factors in absorption and metabolism mechanisms on the drug oral bioavailability of rats and humans. Expert Opin. Drug Metab. Toxicol. 3 469-489. 

Deacetylation. Deacetylation occurs in a number of species, but there is a large difference between species, strains, and individuals in the extent to which the reaction occurs. Because acetylation and deacetylation are catalyzed by different enzymes, the levels of which vary independently in different species, the importance of deacetylation as a xenobiotic metabolizing mechanism also varies between species. This can be seen in a comparison of the rabbit and the dog. The rabbit, which has high acetyltransferase activity and low deacetylase, excretes significant amounts of acetylated amines. The dog, in which the opposite situation obtains, does not. 

W. Lovenberg (Ed.), Iron-Sulfur Proteins, Vol. Ill, Structure and Metabolic Mechanisms, Academic Press, New York (1977). 

It appears that the white musculature of fish is provided with metabolic mechanisms that allow lipids as well as glycogen to contribute energy. Experiments using 14C tracer have shown that triacyl-glycerols in white... 

B. Bioavailability Enhancement by Means of Biochemical/Metabolic Mechanisms... 

Studies in recent years have revealed a number of remarkable drug interactions with irreversible or mechanism-based inhibitors of CYP3A, many of which can be attributed to inhibition of sequential intestinal and hepatic first-pass metabolism. Mechanism-based inhibition involves the metabolism of an inhibitor to a reactive metabolite, which either forms a slowly reversible metabolic-intermediate (MI) complex with the heme moiety or inactivates the enzyme irreversibly via covalent binding to the enzyme catalyzing the last step in the bioactivation sequence. As a result, mechanism-based inhibition is both... 

Foliar uptake of elements is believed to consist of two phases non-metabolic cuticular absorption which is generally considered to be the major route of entry and metabolic mechanisms which account for element accumulation against a concentration gradient. Passsage through the cuticle is possible only by diffusion (Ziegler, 1988 Reiderer, 1991). The second process is responsible for transporting ions across the plasma membrane and into the cell protoplast. 

In summary, then, the above short overview indicates that organisms from very early on probably minimized the threat of ammonia intoxication by metabolic mechanisms which serve to limit the amount of free ammonia in cell/body fluids formed in the first place. However, some formation and accumulation are inevitable. In mammals, and other animals that depend upon the urea cycle, this excess NH4+/NH3 together forms the precursor pool for urea synthesis. 

The metabolism of halogenated organic compounds is related directly to their environmental impact and toxicology. Accordingly, there has been extensive research into metabolic mechanisms, some of which detoxify and remove environmental pollutants, others which are responsible for in vivo toxicity. A brief overview in this subject will be given in this section. 

The rapid advances in analytical chemistry and the detection of ever smaller quantities of material involved in the processes in our bodies mean that our understanding of the metabolic mechanisms and interactions with drugs is becoming more and more sophisticated. The small quantities of carbon monoxide and its presence in the brain, the massive role of nitric oxide and the detection of minute quantities of oxidants and anti-oxidants in the blood and cells are discussed in other chapters. 

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