High Affinity Iron-Transport System

Earhart (39) provide the evidence that in SDS gels the ferric entero-bactin receptor behaves as a component with mol wt 95,000. Both parts of the high affinity iron transport system endogenous to E. coli have now been shown to be under iron repression. Gilchrist and Konisky (76) observed lower levels of colicin la receptor in a heme requiring mutant of E. coli, a result which might be ascribed to an intracellular accumulation of iron. The latter represses formation of the la receptor (66). 

The Fur (Ferric uptake regulation) protein is a negative regulator of the aerobactin-operon and of several other siderophore-mediated, high affinity iron transport systems in... 

Similar to the occurence in animals, iron deprivation in the yeast Saccharomyces cerevisiae induces the expression of a high affinity iron transport system, and the mechanism by which the signal is transduced is partially understood. Ferric iron is reduced to Fe via Frel/Fre2, and subsequently reoxidized and transported into cells by Fet3 and Ftrl, respectively (reviewed in [49], see Chapter 4 and [50]). Fet3 is a multicopper oxidase homologous to ceruloplasmin it requires the protein Ccc2 for... 

The high affinity iron transport system in yeast is composed of an oxidase and a permease. The oxidase converts extracellular ferrous iron to ferric which crosses the... 

Copper occurs in cytochrome oxidase, a key protein in respiratory electron transport, and in plasto-cyanin, which substitutes for the iron protein cytochrome Cg in photosynthetic electron transport in oceanic phytoplankton. It is also an essential component of the high-affinity iron transport system of many eukaryotic algae. Because copper is needed for iron uptake and can metabolically substitute for iron, co-limitations can occur for Cu and Fe, as observed in some diatoms. 

This pathway was first found in microorganisms which produce SA or the related compound 2,3-DHBA. The function of these compounds is different from that in plants. Under aerobic growth conditions, iron occurs in the environment as the highly insoluble Fe(OH)j. To overcome the problem of Fe " deficiency almost all bacteria and fungi have evolved high-affinity Fe transport systems based on the synthesis of low-molecular-mass... 

The ferrous iron produced by the ferrireductases can be transported through either a high affinity or a low afiinity iron transport system. The low affinity iron transport system has a Kta for iron of 30 pM and transports other metals in addition to iron including the potentially toxic metals cadmium and cobalt [25]. The FET4... 

The accumulation of iron is dependent on its transport into the cell. Askwith and Kaplan (Chapter 4) discuss iron transport mechanisms in eukaryotic cells, developing models based on studies carried out in the yeast, Saccharomyces cerevisiae. These cells possess both siderophore-dependent and elemental iron transport systems. The latter system relies on cell surface ferrireductases to convert extracellular ferric chelates to ferrous iron, which can be transported through either a high or low affinity iron transport system. Studies on a high affinity ferrous iron transporter (FET3) revealed that the multicopper oxidase will oxidize ferrous to ferric iron, which is then mobilized across the membrane by a ferric transmembrane permease (Ftrlp). This is a highly specific transport system in yeast it only transports iron. In humans, the copper enzyme, ceruloplasmin, is responsible for the radical-free oxidase activity. This plasma protein oxidizes the ferrous iron that is excreted from cells into the transferrin-usable ferric form. 

A third high-affinity iron-uptake system mediates the accumulation of iron complexed with citrate. Growth of . coli in the presence of citrate induces the production of an outer membrane protein (M 80,500). Genetic analysis of the iron citrate transport system of E. coli located the genes controlling the system, designated fee. Subsequently the /ec locus was subdivided into fecA and /ecS, the former coding for the outer membrane protein. 

Figure 1. Schematic of the two iron transport systems of microorganisms. The high affinity system is comprised of specific carriers of ferric ion (siderophores) and their cognate membrane hound receptors. Both components of the system are regulated by iron repression through a mechanism which is still poorly understood. The high affinity system is invoked only when the available iron supply is limiting otherwise iron enters the cell via a nonspecific, low affinity uptake system. Ferri-chrome apparently delivers its iron by simple reduction. In contrasty the tricatechol siderophore enterobactin may require both reduction and ligand hydrolysis for release...

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