Metabolism integration

As described in the previous section, bile acids have evolved over the last years from regulators of bile acid homeostasis to general metabolic integrators. It is therefore not too surprizing that a number of bile acid-activated signaling pathways have become attractive targets for the treatment of gallstones and other metabolic diseases, such as obesity, type 2 diabetes, hyperlipidemia, and atherosclerosis. 

Given the overwhelming influence of the physical properties of skin in determining bioavailabilities via the dermal route, assessment of dermal penetration is one area in metabolism and toxicology where in vitro methods can be effectively used to predict in vivo results and to screen chemicals. Apparatus and equipment exist that one can use to maintain sections of skin (obtained from euthanized animals or from human cadavers or surgical discard) for such experiments (Holland et al., 1984). These apparatus are set up to maintain the metabolic integrity of the skin sample between two reservoirs the one on the stratum comeum side, called the application reservoir and the one on the subcutaneous side, called the receptor reservoir. One simply places radiolabeled test material in the application reservoir and collects samples from the receptor fluid at various time points. 

Biochemistry of intercellular communication metabolic integration and coordination... 

Kagan, V.E., Ritov, V.B., Tyurina, Y.Y., and Tyurin, V.A., 1998, Sensitive and specific florescent probing of oxidative stress in different classes of membrane phospholipids in hve cells using metabolically integrated cw-parinaric add, Meth. Mol. Biol. 108 71-87. 

Prous Science provides a database for drug discovery and development encompassing all the areas in drug discovery, including metabolism. Integrity enables researchers to combine chemistry and genomics data with pharmacodynamics and pharmacokinetics databases. All the data are cumulated through available public records, literature, conferences, and patents. This database is a very useful system to acquire public information (290). 

Ter-Pogossian MM, Klein MS, Markham J, Roberts R, Sobel BE. Regional assessment of myocardial metabolic integrity in vivo by positron-emission tomography with 1 IC-labeled palmitate. Circulation 1980 61 242-255... 

As complex as the regulation of carbohydrate metabolism is, it is far from the whole story of fuel metabolism. The metabolism of fats and fatty acids is very closely tied to that of carbohydrates. Hormonal signals such as insulin and changes in diet or exercise are equally important in regulating fat metabolism and integrating it with that of carbohydrates. We shall return to this overall metabolic integration in mammals in Chapter 23,... 

New discussion of the role of AMP-dependent protein kinase in metabolic integration... 

While some culture media are formulated to promote cell multiplication (growth media), others only maintain cell structural and metabolic integrity (maintenance media), but do not stimulate cell division. Media prepared with highly purified compounds and with known composition are designated chemically defined media. These are particularly attractive for biopharmaceutical production, because they are less vulnerable to contamination and quality control is easier. Nevertheless, these media can be expensive. 

Sato A, Nakajima T. 1979a. Dose-dependent metabolic integration between benzene and toluene in vivo and in vitro. Toxicol Appl Pharmacol 48 249-256. 

For any nutrient, there is a range of intakes between that which is clearly inadequate, leading to clinical deficiency disease, and that which is so much in excess of the body s metabolic capacity that there may be signs of toxicity. Between these two extremes is a level of intake that is adequate for normal health and the maintenance of metabolic integrity, and a series of more precisely definable levels of intake that are adequate to meet specific criteria and may be used to determine requirements and appropriate levels of intake. These follow. 

Adequate body reserves and normal metabolic integrity. This is the (possibly untestable) goal. Both immune function and rninirnization of DNA damage offer potential methods of assessing optimum micronutrient status, but both are affected by a variety of different nutrients and other factors (Fenech, 2001). 

Artho, A., BavestreUo, G., Burlando, B., and Sara (1993). Metabolic integration between symbiotic cyanobacteria and sponges A possible mechanism. Mar. Biol. 117, 159—162. 

Figure 23.18 Metabolic integration of nitrogen metabolism. The urea cycle, gluconeogenesis, and the transamination of oxaloacetate are linked by fumarate and aspartate.

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