Zinc transport proteins

Zhao, H. and Eide, D. (1996). The yeast ZRT1 gene encodes the zinc transporter protein of a high-affinity uptake system induced by zinc limitation, Proc. Natl Acad. Sci., 93, 2454-2458. 

Keywords Zinc Early Alzheimer s disease Mild cognitive impairment Zinc transporter proteins Amyloid beta peptide Neurodegeneration... 

O Dell BL. 1992. Cysteine-rich intestinal protein (CRIP) A new intestinal zinc transport protein. Nutr Rev 50(8) 232-233. 

Unfortunately, the pharmacology of chloride channels is poorly developed. Specific and highly useful inhibitors or modulators (e.g. strychnine, picrotoxin, diazepams) are only available for ligand-gated chloride channels (but these are covered in a different chapter). There are several chloride channel inhibitors such as the stilbene-disulfonates DIDS and SITS, 9-antracene-carboxylic acid (9-AC), arylaminobenzoates such as DPC and NPPB, niflumic acids and derivates, sulfony-lureas, and zinc and cadmium. All of these inhibitors, however, are not veiy specific. Several of these inhibitors (e.g. DIDS) inhibit many chloride channels only partially even at millimolar concentrations and have effects on other types of transport proteins. 

Transport proteins (channels) for chloride and zinc Vacuolar proton pump Components of synaptic vesicles to mediate the chloride flux for glutamate uptake and zinc uptake in most synaptic vesicles. Zinc transporter is homologous to endosomal and plasma membrane zinc transporters chloride transporters remain to be identified. Protein complex of more than 12 subunits. Constitutes the largest component of synaptic vesicles and establishes... 

Fraser, W.D., Taggart, D.P., Fell, G.S. et al. (1989) Changes in iron, zinc and copper concentrations in serum and in their binding transport proteins after cholecystectomy and cardiac surgery. Clin. Chem., 35, 2243-2247. 

The Isolated, vascularly perfused rat intestine system has been used to investigate the influence of various zinc-binding ligands on zinc absorption. With this approach the functional integrity of the intestine with respect to several minerals, including calcium, iron and zinc uptake, and subsequent transfer of these minerals to their respective serum transport proteins is maintained (32,33). The intestinal perfusion system allows the simultaneous measurement of both mucosal zinc uptake (retention) and transfer to the portal circulation (absorption), and thus provides detailed information on the nature of the mechanisms of both uptake from the lumen and transfer to albumin in the portal circulation. 

Competition for Transport on a Circulating Carrier-Protein (J). Once across the serosal border, zinc must still be bound by a transport protein to carry It through the portal circulation, away from the Intestine. There Is debate as to whether this role Is played by transferrin (11) or by albumin (12,13). In either case, the presence of excess metal(s) that bind to the same site on the portal transport protein as zinc would Impede the passage of zinc Into the systemic circulation. 

Zinc homeostasis is largely regulated by its uptake and loss through the small intestine. Although a number of zinc transporters and binding proteins have been identified in villus epithehal cells, a full understanding of zinc absorption is not yet at hand. 

White KJ, Kiser PD, Nichols DE, Barker EL (2006) Engineered zinc-binding sites confirm proximity and orientation of transmembrane helices I and III in the human serotonin transporter. Protein Sci 15 2411-2422... 

Zinc and Zinc Transport and Sequestration Proteins in the Brain in the Progression of Alzheimer s Disease... 

In general, Zn homeostasis is maintained by three families of proteins (a) met-allothioneins (MT) that quickly bind, sequester, and hold Zn after influx into the cytoplasm, (b) Zrt-Irt-like (ZIP) proteins that likely mediate Zn influx into the cell, and (c) zinc transporter (ZnT) proteins that mediate efflux of cytoplasmic Zn to the extracellular space or sequestration in intracellular organelles. 

Takeda A, Minami A, Takefuta S, Tochigi M, Oku N (2001) Zinc homeostasis in the brain of adult rats fed zinc-deficient diet. J Neurosci Res 63 447-452 Taylor KM, Morgan HE, Johnson A, Hadley LJ, Nicholson R1 (2003) Structure-function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters. Biochem J 375 51-59... 

Zinc efflux is mediated by a zinc exporter known as ZntA (Zn + transport or tolerance), a membrane protein which was identified through studies of bacterial strains that were hypersensitive to zinc and cadmium. Sequence inspection revealed that ZntA was a member of the family of cation transport P-type ATPases, a major family of ion-translocating membrane proteins in which ATPase activity in one portion of the protein is used to phophorylate an aspartate within a highly conserved amino acid sequence, DKTG, in another portion of the protein. The cysteine rich N-terminus of these soft metal transport proteins contains several metal-binding sites. How the chemical energy released by ATP hydrolysis results in metal ion transport is not yet known, in part because there is only partial information about the structures of these proteins. The bacterial zinc exporter also pumps cadmium and lead and is therefore also involved in protection from heavy metal toxicity (see Metal Ion Toxicity). 

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