Heme synthetase deficiency

Bonkowsky HL, Bloomer JR, Ebert PS, Mahoney MJ (1975) Heme synthetase deficiency in human protoporhyria Demonstration of the deficit in liver and cultured skin fibroblasts. J Clin Invest 56 1139-1148 De Vemeuil H, Aitken G, Nordmann Y (1978) Familial and sporadic porphyria cutanea two different diseases. Hum Genet 44 145-151... 

The controls of the heme-BCHL biosynthetic chain are summarized in Fig. 10. As discussed above, at least three kinds of control regulate ALA-synthetase activity. One is by heme acting as corepressor in the synthesis of this enzyme (2). Another is by heme acting as inhibitor of the enzyme (3). A third is by activation possibly of a precursor ALA-synthetase, the ratio of activator to inhibitor serving to control the degree of activation (1). Another control is somewhere between coproporphyrinogen and heme as revealed in methionine deficiency (4). In addition there is a control of the enzymes of the Mg branch (5), in contrast to those enzymes from ALA to heme. The enzymes of the Mg... 

It is believed that at least in some cases of porphyria a partial block of the biosynthetic pathway is associated with the increased activity of ALA synthetase. Since heme seems to be a natural inhibitor of the synthetase, it is conceivable that in those cases the primary defect results in a deficiency in heme synthesizing enzyme [215]. 

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