Early Stages in the Metabolism of Iron 195 



Essentially nothing is known of the structure and origin of the active 

 centres of the non-haem iron enzymes. 



The special problems which arise in iron metabolism, as contrasted, for 

 example with copper metabolism, can be illustrated by comparison of the 

 characteristics and behaviour of the two elements in question. In the case of 

 copper it is certain that smaller quantities are required by living tissues, the 

 somewhat greater solubility of the hydroxide (saturated water solution of 

 cupric hydroxide is > 10~^ m at 25°, Seidell, 1940) and, finally, the ubiquitous 

 a-amino carboxylic acid structure provides an effective ligand capable of 

 holding the cupric ion in solution at physiological pH. 



In the present paper, results will be presented for certain experiments dealing 

 with the early stages of iron metabolism in micro-organisms. The latter form 

 of life has been chosen for investigation on account of the well-known 

 metabolic flexibility characteristic of unicellular organisms; however, in 

 spite of this advantage, it must be recognized that micro-organisms as experi- 

 mental subjects suffer from the fact that each species may exhibit certain 

 metabolic variations. This will effectively preclude the formulation of sweeping 

 generalities about the detailed mechanism of iron metabolism in all forms 

 of life. 



The technique employed in the present instance has been that of cultivation 

 of the aerobic micro-organisms Bacillus subtilis and Ustilago sphaerogena in 

 the presence of diminished levels of iron. Such very aerobic species can be 

 expected to have a reasonably high requirement for iron and a correspondingly 

 well-developed system for the intermediary metabolism of this element. This 

 statement is particularly true for Ustilago sphaerogena since this organism is 

 known to form large quantities of cytochrome c (Grimm and Allen, 1954). 

 The growth of such cells under conditions of iron deprivation provides 

 valuable information about the early stages of iron metabolism. At very 

 low levels of iron there is sparse growth, a feeble metabolism and essentially 

 nothing can be learned about the intimate processes of iron utilization. 

 Similarly, at abnormally high levels of iron, the substances usually involved as 

 intermediates in iron metabolism may be produced in greatly diminished 

 quantities in spite of the excellent cell yields. On the other hand, at inter- 

 mediate levels of iron, three possible metabolic adjustments come into play 

 which lead to the accumulation and excretion of iron-complexing agents : 



(i) The biosynthesis of specific ferric complexing agents, normally com- 

 petitively inhibited and maintained at a low level by the presence of a 

 variable amount of the ferric chelate, becomes a major metabolic 

 activity of the cell. 



(ii) The deficiency of iron creates a metabolic block, the latter being 

 manifested by the appearance of iron-complexing products which 

 normally require iron for their further metabolism. 



