The reaction occurs in two steps. This is the rate-limiting reaction of heme synthesis in all tissues, and it is therefore tightly regulated. There are two major means of regulating the activity of the enzyme. The first is by regulating the synthesis of the enzyme protein. This is important because its half life is only about one hour.
Enzyme synthesis is repressed by heme and hematin.
Only the 5-beta product affects synthesis of ALA synthase. Since the 5-beta reductase appears at puberty, some porphyrias are not manifested until this age. Summary of regulation of heme synthesis. The second control is feedback inhibition by heme and hematin, presumably by an allosteric mechanism. Hence, heme has a dual role in decreasing its own rate of synthesis.