Assimilation in Mammals

Since in mammals, metals need first to be assimilated from dietary sources in the intestinal tract and subsequently transported to the cells of the different organs of the body through the bloodstream, we will restrict ourselves in this section to the transport of metal ions across the enterocytes of the upper part of the small intestine (essentially the duodenum), where essentially all of the uptake of dietary constituents, whether they be metal ions, carbohydrates, fats, amino acids, vitamins, etc., takes place. We will then briefly review the mechanisms by which metal ions are transported across the plasma membrane of mammalian cells and enter the cytoplasm, as we did for bacteria, fungi, and plants. The specific molecules involved in extracellular metal ion transport in the circulation will be dealt with in Chapter 8. 

FIGURE 7.18 The transferrin to cell cycle. HOLO-TF diferric transferrin TfR, transferrin receptor DMTl, divalent metal transporter. 

Serum iron is delivered to cells via the transferrin to cell cycle (Fig. 7.18). The drferric-transferrin molecule binds to its receptor and the complex is invaginated into clathrin-coated pits, which fuse with the target membranes of endosomes delivering the vesicle contents into the interior of the endosome. The pH of the endosome is reduced to around 5—6 by the action of an ATP-dependent proton pump, and at this pH iron is released from transferrin 

Copper uptake across the gastrointestinal tract is poorly understood — most probably utihsing the divalent cation transporter DMTl. At the cellular level, Cu is imported across the plasma membrane of mammalian cells as Cu, by members of the CTR family. The CTR family of proteins have been found in yeast and plants, as we saw, but also in humans and other mammals. They contain several methionine-rich motifs at their N-terminus, and conserved cysteine and histidine residues at their C-terminus. Unusually, CTR proteins can mediate the uptake of platinum anticancer drugs into mammalian cells (see Chapter 22). 

The ZIP family are involved in Zn transport into the cytosol, mostly across the plasma membrane. Although the human genome encodes 14 ZIP-related proteins, Z1P4 appears to mediate Zn uptake. It s involvement in dietary Zn uptake into intestinal enterocytes is well estabhshed, and mutations in Z1P4 have been found in patients with acrodermatitis enteropathica, a recessive disorder of Zn absorption which results in Zn deficiency. DMTl is probably also involved in the transport of dietary zinc across the brush border membrane of the intestine. 

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Glutamine synthetase is found in all organisms. In addition to its importance for NHj assimilation in bacteria, it has a central role in amino acid metabolism in mammals, converting toxic free NHj to glutamine for transport in the blood (Chapter 18). 

Most of the discrimination between inorganic and methylmercury thus occurs during trophic transfer, while the major enrichment factor is between water and the phytoplankton. This also has been reported for the diatom Thalassiosura weissflogii in a marine food chain (Mason et al. 1996). Methylmercury was accumulated in the cell cytoplasm, and its assimilation by copepods was 4 times more efficient than the assimilation of inorganic mercury. Bioaccumulation has been demonstrated for predator fish in both freshwater and marine systems and in marine mammals (see Section 5.4.4). Bioaccumulation of methylmercury in aquatic food chains is of interest, because it is generally the most important source of nonoccupational human exposure to this compound (EPA 1984b WHO 1990, 1991). 

We therefore discuss in succession the assimilation of metal ions by bacteria, by plants, and fungi, and finally by mammals, with a particular focus on man. In most cases, we consider systems involved in iron uptake and then those involving copper and zinc. This is based on the simple logic that these are the three metals for which the assimilation systems are the best characterized. We begin with a brief outline of inorganic biogeochemistry and then discuss a few other metals where sufficient information is available. The specific cases of Na" ", K, and will be dealt with in Chapters 9 and 11. We remind the reader that uptake systems for the essential metalloids B and Si and their toxic homologues As and Sn were already discussed in Chapter 1. 

Despite the existing evidence attesting to the safety of dietary astaxanthin, little is known about the bioavailability and metabolism of this carotenoid in humans. Several steps are involved in the assimilation of carotenoids by mammals, including transfer from the food matrix, transfer to lipid micelles in the small intestine, uptake by intestinal mucosal cells, transport to the lymph system, and eventually, deposition of the carotenoid or its metabolites in specific tissues. " A number of factors can influence the progression of these steps, including the nature of the food matrix, " the structure of the carotenoid (including potential esterification and the nature of its isomeric composition), the presence of other carotenoids, " and the amount and types of lipids in the diet. Overall, human metabolism of astaxanthin should be somewhat similar to that of the other xanthophylls, but subtle differences are expected. 

Arachidonic acid is present in high concentrations in ester form in most animal fats and so can be assimilated by man directly in his diet. Alternatively, mammals may biosynthesize arachidonic acid from linoleic acid via desaturation to y-linolenic acid, chain elongation to dihomo-y-linolenic acid, and then further desaturation to arachidonic acid. 

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