Absorption, Transport, and Metabolism

Vitamin E is absorbed as free tocopherol, along with other fat-soluble vitamins and dietary lipids. Tocopheryl acetate, the form commonly used for dietary supplementation, is hydrolyzed before absorption. Uptake requires bile salts. A selective impairment of vitamin E absorption without malabsorption of other fat-soluble vitamins has been identified it was corrected after a large oral intake of the vitamin. Patients with chronic fat malabsorption and abetalipoproteinemia (Chapter 20) may develop vitamin E deficiency. 

About 75% of the absorbed vitamin E enters the lymphatics in chylomicrons, and the rest in other lipoproteins. In plasma, vitamin E is carried by lipoproteins and erythrocytes. In humans, vitamin E is present in greatest amounts in adipose tissue, liver, and muscle. Its principal excretory route is the feces, probably by way of bile. 

Vitamin E may also possess antiatherogenic properties. In vitro, studies have shown that oxidized low-density lipoproteins (LDL) are proatherogenic (Chapter 20) and vitamin E retards LDL oxidation. Thus, it is thought vitamin E supplementation might reduce the morbidity 

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Measurement of exposure can be made by determining levels of toxic chemicals in human serum or tissue if the chemicals of concern persist in tissue or if the exposure is recent. For most situations, neither of these conditions is met. As a result, most assessments of exposure depend primarily on chemical measurements in environmental media coupled with semi-quantitative assessments of environmental pathways. However, when measurements in human tissue are possible, valuable exposure information can be obtained, subject to the same limitations cited above for environmental measurement methodology. Interpretation of tissue concentration data is dependent on knowledge of the absorption, excretion, metabolism, and tissue specificity characteristics for the chemical under study. The toxic hazard posed by a particular chemical will depend critically upon the concentration achieved at particular target organ sites. This, in turn, depends upon rates of absorption, transport, and metabolic alteration. Metabolic alterations can involve either partial inactivation of toxic material or conversion to chemicals with increased or differing toxic properties. 

As Co-containing organometallic compounds, cobalamins are unique in nature, and they have a genetic history of more than four billion years. Their biosynthesis, absorption, transport, and metabolism have been well documented in organisms of both marine and terrestrial origin.1110-1112... 

Several studies have investigated the absorption, transport, and metabolism of resveratrol in vitro and ex vivo. They are summarized in Table 13.1. 

Olson, J. 1994. Absorption, transport, and metabolism of carotenoids in humans. Pure Appl. 

TCI has a high affinity for and is about 90% saturated with cobalamin, while TCIII binds less strongly and is largely unsaturated. However, TCII binds newly absorbed cobalamins, and the TCII-cobalamin complex appears to deliver cobalamin to peripheral tissues (Figure 38-18). TCII accounts for most of the unsaturated vitamin B12 binding capacity of serum. Therefore, cobalophilins (except TCII see below) probably have a minimal role in cobalamin absorption, transport, and metabolism. Thus, members of the family with congenital cobalophilin deficiency showed no symptoms of vitamin B12 deficiency despite a very low serum concentration of the vitamin secondary to the absence of TCI. 

The absorption, transport and metabolism of TOH in animals has been reviewed on several occasions (Bjomeboe et al., 1989 Drevon, 1991). TOH is transferred from circulating lipoproteins to the brain, spinal cord and peripheral nerves and muscle by unknown mechanisms (Sokol, 1989). There is no uniform distribution of TOH in the central and peripheral nervous system (Vatassery etal., 1984a). 

Drevon, C.A. (1991) Absorption, transport and metabolism of vitamin E. Free Radical Res. Commun. 14 229-246. 

This volume gives an overview of the current status and an outlook to future more reliable predictive approaches. It is subdivided in five sections dealing with studies of membrane permeability and oral absorption, drug dissolution and solubility, the role of transporters and metabolism in oral absorption, computational approaches to drug absorption and bioavailability, and finally with certain drug development issues. 

Smith P, Mirabelli C, Fondacaro J, Ryan F, Dent J (1988) Intestinal 5-fluorouracil absorption Use of Ussing chambers to assess transport and metabolism. Pharm Res 5 598-603. 

Cultured nasal cells are reliable models for drug transport and metabolism studies, since they are known to express important biological features (e.g. tight junctions, mucin secretion, cilia, and various transporters), resembling those found in vivo systems. Moreover, easy control of experimental conditions as well as separation of the permeation step from the subsequent absorption cascade is also possible. A relatively simple primary culture condition using human nasal epithelial cells for in vitro drug transport studies has been established and applied in transport and metabolism studies of drugs. It is known that the culture condition and/or selection of culture media are critical in the recapitulation of well-differentiation features of in vivo nasal mucosal epithelium [46],... 

Mizuma, T., A. Koyanagi, and S. Awazu. 1997. Intestinal transport and metabolism of analgesic dipeptide, kyotorphin Rate-limiting factor in intestinal absorption of peptide as drug. Biochim... 

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