Molecular mechanism of regulation of siderophore-mediated iron assimilation.

This review describes a molecular mechanism for regulation of one pathway of microbial assimilation of iron, an element which may well be a nutrient required by all living cells. Unlike organic compounds, minerals cannot be synthesized and must be acquired from the environment. In contrast to amino acids, fatty acids, and monosaccharides, all of which can be accumulated in the form of relatively innocuous polymers, living tissues in general seem to have little capacity to store metal ions and hence organisms prefer to limit the uptake at the membrane level. This concept, as it applies to iron, is firmly rooted in the pioneering work of McCance and Widdowson who, according to Underwood (55), concluded that the amount of the element "must be regulated by controlled absorption." We have lately come to recognize that there are special reasons why aerobic and facultative anaerobic organisms should carefully meter the amount of iron taken up. This is because surplus iron may find its way into coordination sites where it can generate oxidizing radicals. While the following equation may not do full justice to all of the complications inherent in Haber-Weiss-Fenton chemistry, they do nonetheless illustrate the propensity of iron (18) to catalytically promote hydroxyl radical production from superoxide and peroxide, species which inevitably arise from partial reduction of molecular oxygen: O2 + Fe3" = 02 + Fe2+; 202 + 2H+ = H202 + 02; H202 + Fe2+ = Fe3+ + OH+ OH . The human body contains 4 to 5 g of iron, of which amount roughly three-quarters is in hemoglobin and virtually all of the remainder is stored in the liver as ferritin. This leaves only trace quantities for enzyme and transport forms of iron.