The metabolic abnormalities in porphyria

With the recognition that there is abnormal excretion of certain porphyrins in the hereditary porphyrias it was assumed that as in other metabolic errors, the abnormalities resulted from an enzyme block either in an associated pathway diverting more substrate to porphyrin synthesis or in porphyrin utilization leading to an accumulation of metabolic precursors. However, further observations showed that neither of these hypotheses was tenable. 

Later experiments with tissue cultures showed how substances producing porphyria in experimented animals could induce ALA-synthetase formation de novo [80, 81]. 

It seems likely that under normal conditions there is a mechanism for repression of this enzyme induction, and it has indeed been shown that haem and other metal-containing porphyrins repress ALA-synthetase induction in foetal liver cells [82]. 

This is the first example to be recognized of a genetically determined metabolic abnormality which is characterized by an overproduction of an enzyme. Granick [83] has proposed that the inherited defect resides in the operator of the structural gene for ALA-synthetase [84, 85]. 

The extrapolation to naturally occurring madadies of the experimented studies on which these hypotheses are based is justified, for example, by the demonstration of an increase of 

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