Absorption metabolic activity

The mucosa of the GIT represents an interface between the external and internal environments. The expansive surface area is necessary for the efficient hydrolysis of foodstuffs and the absorption of energy and nutrients. The mucosa also influences the systemic availability of non-nutrient compounds in the diet, both beneficial and detrimental. Digestion and absorption of glucosinolates are critical determinants of health benefits (see Chapter 4) Similarly, the bioavailability and health benefits of phytoestrogens, such as genistein (see Chapters 5 and 10) are at least partly dependent on the carrier-mediated processes of absorption associated with the GIT (Oitate et al, 2001). Moreover, the metabolic activities of the mucosa can influence the systemic concentrations and forms of dietary phytochemicals, as exemplified by research with soy isoflavones (Andlauer et al., 2000). 

FIG. 2 Mechanisms of drug transfer in the cellular layers that line different compartments in the body. These mechanisms regulate drug absorption, distribution, and elimination. The figure illustrates these mechanisms in the intestinal wall. (1) Passive transcellular diffusion across the lipid bilayers, (2) paracellular passive diffusion, (3) efflux by P-glycoprotein, (4) metabolism during drug absorption, (5) active transport, and (6) transcytosis [251]. 

Several studies have been carried out to investigate the effect of pH on azo dye decolorization. In these assays, the decrease of absorbance at the wavelength corresponding to the maximum absorption for each dye is used as the method to evaluate the effectiveness of decolorization. Unfortunately, in most cases it is not clear if the isosbestic point of each dye was taken into account, and so it cannot be well understood if the different decolorization rate at different pH is due to a physical factor or to a differently influenced metabolic activity. 

Metabolism of fenvalerate proceeds by way of oxidation and hydrolysis to produce metabolites considered pharmacologically inactive or inferior to the parent compound. Insects and fish are extremely susceptible to fenvalerate when compared to mammals and birds. Interspecies differences are associated with rates of metabolism, excretion, absorption, esterase activity, and neurosensitivity. 

In a more traditional pharmaceutical setting, this characterization would be done during preformulation studies. With the availability of automation and the ability to conduct most of these experiments with small quantities of material, more preformulation activities are being shifted earlier into drug discovery. Recently, Balbach and Korn37 reported a "100 mg approach" to pharmaceutical evaluation of early development compounds. Additional absorption, metabolism, distribution, elimination, and toxicity38 screens may also be conducted at this stage. 

Figure 5-4. Metabolic activities of major organs in the fed state. The relative activities of major metabolic pathways or processes in each of the organs are indicated by their font sizes. The exchange of nutrient materials and fuel molecules through the bloodstream illustrates the interrelationships of these organs. In the absorptive condition, all organs share the bounty of nutrients made available by digestion of food by the intestine. PPP, pentose phosphate pathway FA, fatty acids TAG, triacyl-glycerol.

Figure 5-5. Metabolic activities of major organs during a short-term fast. The importance of the liver in providing glucose to support the brain and other glucose-requiring organs in the post-absorptive state is illustrated. The body relies on available glycogen stores as a ready source for glucose as fuel. PPP, pentose phosphate pathway FA, fatty adds TAG, triacylglycerol.

Molecular size J, incumbrance area of planar molecule <100 or >135 A2 Affect absorption and metabolic activation... 

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