TETRAPYRROLES 47 



lation occurs only in the later stages of growth and the quantities of 

 porphyrin formed far exceed the amount of tetrapyrrole, as hemes and 

 bacteriochlorophyll, which are formed with adequate iron (26), Iron 

 acts catalytically in preventing porphyrin formation and this could 

 suggest that it is needed to form a compound which controls an early 

 step in the synthesis of porphyrins by negative feedback inhibition. 

 Work with whole cells and partly purified preparations of ALA synthe- 

 tase of Rps. spheroides suggest that heme may exert such a controlling 

 function (48,49), The enzyme is inhibited by low concentrations of 

 hemin (down to 10"^ M); porphyrin accumulation by intact cells is in- 

 hibited by hemin when glycine and succinate are the substrates but 

 conversion of ALA to porphyrin is unaffected. Under normal conditions 

 hemes within the cell are mostly if not entirely present as hemopro- 

 teins, Hemoproteins (hemoglobin and myoglobin) also inhibit ALA 

 synthetase and it is in this form that hemes may function in the control 

 mechanism. 



Besides inhibiting the action of ALA synthetase hemin also represses 

 synthesis of this enzyme by growing cultures of Rps. spheroides (50), 

 The conclusion from these various observations is that the intracell- 

 ular level of hemes, probably as hemoproteins, participate in the con- 

 trol of tetrapyrrole synthesis by influencing both the synthesis and the 

 action of the synthetase. The effect of hemin on the synthetase does not, 

 however, satisfactorily account for all the effects of iron observed 

 with Rps. spheroides , in particular the action of iron in promoting 

 bacteriochlorophyll synthesis, 



Bacteriochlorophyll might also act as a controlling factor. Free 

 bacteriochlorophyll does not inhibit ALA synthetase but this may not 

 be significant since in the cell it exists in combination with the chroma- 

 tophore complex. Gibson et al. (33) have suggested that an intermediate 

 between magnesium protoporphyrin methyl ester and bacteriochloro- 

 phyll may act as a feedback inhibitor of ALA synthetase and their ob- 

 servations on the effect of ethionine on Rps. spheroides support this. 

 This analogue inhibits bacteriochlorophyll synthesis, probably by in- 

 terfering with the methylation step, but stimulates the accumulation 

 of coproporphyrin. 



Since the path of heme and chlorophyll synthesis is common up to 

 the protoporphyrin stage and since photosynthetic organisms must form 

 both types of tetrapyrrole for photosynthetic development, control 

 mechanisms might be expected to operate at the branch joint leading 

 to iron and magnesium protoporphyrins. Information about this must 

 await knowledge of the enzyme systems catalysing the insertion of the 

 metals into the tetrapyrrole structure. 



Light intensity and oxygen. 



On teleological grounds it is an advantage for an organism, which 

 relies onlightfor energy, to be able to increase or decrease its chloro- 



