Absorption and metabolism

Irrespective of the physical form of the carotenoid in the plant tissue it needs to be dissolved directly into the bulk lipid phase (emulsion) and then into the mixed micelles formed from the emulsion droplets by the action of lipases and bile. Alternatively it can dissolve directly into the mixed micelles. The micelles then diffuse through the unstirred water layer covering the brush border of the enterocytes and dissociate, and the components are then absorbed. Although lipid absorption at this point is essentially complete, bile salts and sterols (cholesterol) may not be fully absorbed and are not wholly recovered more distally, some being lost into the large intestine. It is not known whether carotenoids incorporated into mixed micelles are fully or only partially absorbed. 

A small but variable proportion of the carotenoids with one or two P-ionone rings (mainly P-carotene) are cleaved in the enterocytes to produce retinol (vitamin A). This process is very tightly controlled, so that too much vitamin A is not produced, although the control mechanism is not clear. Some cleavage of P-carotene can also occur in the liver, but this does not account for the turnover of P-carotene in the body. Small amounts of carotenoids are subject to enterohepatic circulation, but this does not account for losses. 

The mechanisms of the metabolism and excretion of P-carotene are not clear, other than the identification of a number of partially oxidised intermediates found in plasma (Khachik et al., 1992). It is assumed that the carotenoids are metabolised in a manner analogous to the P-oxidation of fatty acids although there is no evidence for this. 

It is well known that excessive intake of P-carotene may lead to carotenodermia (yellow skin), and it is undoubtedly the case that some carotenoid is directly lost via the skin or through photo-oxidation in the skin. As far as is known the carotenoids are not cytotoxic or genotoxic even at concentrations up to 10 times the normal plasma concentration which may cause carotenodermia. However, they are associated with amenorrhoea in girls who may be consuming bizarre diets and, in long-term supplementation studies, with an increase in lung cancer (The Alpha-tocopherol, Beta-carotene Cancer Prevention Study Group, 1994). 

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WANG X D (1994) Review absorption and metabolism of beta-carotene , JAm Coll Nutr, 13, 314-25. 

ANDLAUER w, KOLB J and fOrst p (2000), Absorption and metabolism of genistin in the isolated rat small intestine. FEES Lett. 475, 127-30. 

LIU Y and HU m (2002) Absorption and metabolism of flavonoids in the caco-2 cell culture model and a perfused rat intestinal model. Drug Metab Dispos. 30 (4) 370-77. 

In this model, no attempt is made to reproduce the in vivo physiochemical conditions occurring in the lumen of the human small intestine during digestion. This cell culture model only provides information about the intestinal absorption and metabolism processes of the compound. Using this cell culture system in con-... 

Among all food pigments, we have the most knowledge about the carotenoids related to their absorption and metabolism on a molecular basis. 

During, A. and Harrison, E.H., Intestinal absorption and metabolism of carotenoids insights from cell culture. Arch. Biochem. Biophys., 430, 77, 2004. 

Wu, X., Cao, G., and Prior, R.L., Absorption and metabolism of anthocyanins in elderly women after consumption of elderberry or blueberry, J. Nutr, 132,1865, 2002. Matsumoto, H. et al.. Orally administered delphinidin 3-rutinoside and cyanidin 3-rutinoside are directly absorbed in rats and humans and appear in the blood as the intact forms, J. Agric. Food Chem., 49, 1546, 2001. 

Tsuda, T., Horio, R, and Osawa, T., Absorption and metabolism of cyanidin 3-0-beta-D-glucoside in rats, FEBS Lett., 449, 179, 1999. 

Selectivity between wheat and Galium aparine is based on differences in deposition, absorption and metabolism in both plants. 

FIGURE 29-2. Levodopa absorption and metabolism. Levodopa is absorbed in the small intestine and is distributed into the plasma and brain compartments by an active transport mechanism. Levodopa is metabolized by dopa decarboxylase, monoamine oxidase, and catechol-O-methyltransferase. Carbidopa does not cross the blood-brain barrier. Large, neutral amino acids in food compete with levodopa for intestinal absorption (transport across gut endothelium to plasma). They also compete for transport across the brain (plasma compartment to brain compartment). Food and anticholinergics delay gastric emptying resulting in levodopa degradation in the stomach and a decreased amount of levodopa absorbed. If the interaction becomes a problem, administer levodopa 30 minutes before or 60 minutes after meals. 

Drugs can affect thyroid function in a number of ways.41 Effects of drugs on thyroid hormone protein binding, LT4 absorption, and metabolism have been discussed previously. Several commonly used medications can alter thyroid hormone secretion. 

No studies were located that examined the toxicokinetics of mineral oil, organophosphate ester, or polyalphaolefin hydraulic fluids in humans or animals, with the exception of a study examining absorption in rats after exposure to a hydraulic fluid containing 99.9% cyclotriphosphazene (Kinkead and Bashe 1987) and the absorption and metabolism of Reolube HYD46, another organophosphate hydraulic fluid (Ciba-Geigy 1985). This section, therefore, discusses available information on the toxicokinetics of major components of these classes of hydraulic fluids or of materials that maybe expected to display similar toxicokinetic properties based on similar physical and chemical characteristics. It should be emphasized that many hydraulic fluids are complex mixtures of chemicals that may include some chemicals which may not share toxicokinetic properties with the major components. 

L Rivera-Calimlim, CA Dujovne, JP Morgan, L Lasagna, JR Bianchine. Absorption and metabolism of L-dopa by the human stomach. Eur J Clin Invest 1 313-320, 1971. 

Borchardt, R. T. Smith, P. L. Wilson, G., Models for Assessing Drug Absorption and Metabolism, Plenum Press, New York, 1996. 

Colonic Drug Absorption and Metabolism, edited by Peter R. Bieck... 

PJ Sinko, GD Leesman, GL Amidon. Mass balance approaches for estimating the intestinal absorption and metabolism of peptides and analogues Theoretical development and applications. Pharm Res 10 271-275, 1993. 

Carotenoid absorption and metabolism have been comprehensively reviewed (Erdman et al., 1993 Parker, 1996 van Vliet, 1996 Furr and Clark, 1997 Yeum and Russell, 2002) and this chapter will focus only on recent advances in these areas. A particular emphasis will be placed on studies that used in vitro and cell culture models as tools to understand better the mechanisms of absorption on the molecular level. 

Artursson, P. and R. T. Borchardt. Intestinal drug absorption and metabolism in cell cultures Caco-2 and beyond, Pharm. Res. 1997, 34, 1655-1658... 

Griffiths, R., Lewis, A., Jeffrey, P., Models for drug absorption in situ and in conscious animals, in Models for Assessing Drug Absorption and Metabolism. Borchard, R. T., Smith, P. L., Wilson, G. (eds), Plenum Press, New York, 1996, pp. 67-84. 

Petri, N., Tannergren, C., Bennett, R. N., Holst, B., Bao, Y. et al., Intestinal absorption and metabolism of sulforaphane and quercetin as well as regulation of phase II enzymes in human jejunum in vivo and in Caco-2 cells, Drug Metab. Dispos. 2003 (in press). 

In vitro kinetic constants obtained from homogenate or whole-cell experiments under controlled conditions were used, and the constants were scaled to the in vivo scenario using appropriate physiological scale factors. Figure 18.6 shows our simulated results for absorption and metabolism of midazolam when dosed with and without grapefruit juice. Midazolam is metabolized by the gut and liver by cytochrome 3A4. Saquinavir is also metabolized in the gut and liver by 3A4, and it is also a substrate for efflux by P-gp. Figure 18.7 shows our simulated results for absorption and metabolism of saquinavir when dosed with and without grapefruit juice. In both cases, it can be seen that the simulation correctly predicts the... 

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