Human Hepatic Porphyria and Increased ALA-Synthetase

After it was established that ALA-synthetase was greatly increased in chemical porphyria, it was shown by Tschudy et al. [71] and by Nakao et al. [72] that in the case of AIP patients the fiver had a five-to tenfold greater level of ALA-synthetase than normal. This result confirmed the idea that a defective control on the activity of hepatic ALA-synthetase was an important characteristic of this disease. 

The half-life of ALA-synthetase and its mRNA have been found in the rat to be about 1 hour for each [Tschudy et al., 73]. Similar lifetimes 

ALA-synthetase has one of the shortest half-lives yet reported for any mammalian liver enzyme, even the inducible ones. In contrast, the half-lives of two other mitochondrial enzymes, alanine and ornithine-amino transferases, inducible by the corticosteroid prednisolone acetate in a concentration of 0.5 mg/rat/day was 17 to 24 hours [75]. The short half-life of ALA-synthetase apparently depends on other cell constituents. When mitochondria from induced guinea pigs were isolated, the activity of their ALA-synthetase was maintained constant over a period of at least 5 hours [35] this activity may have finally not been limited by the stability of the enzyme itself but by the succinyl-CoA-synthesizing mechanism of the mitochondria. These facts suggest that there may be an active process of ALA-synthetase destruction which occurs in the cells but not necessarily in the isolated mitochondria, and which is not affected by the inducing chemicals such as DDC or AIA. 

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