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It is generally accepted that the major organs producing heme are erythroid cells and the liver. delta-Aminolevulinate synthase (ALAS) plays the key role to regulate heme biosynthesis in the liver as well as in erythroid cells. In the liver, nonspecific (or housekeeping) isozyme of ALAS (ALAS-N) is expressed to be regulated by its end product, heme, in the negative feedback manner. Not only erythroid isozyme of ALAS (ALAS-E) but also ALAS-N is expressed in erythroid tissues, and are regulated by distinctive manners. For example, heme regulates ALAS-N and ALAS-E in the negative and in the positive feedback manner, respectively. In this article, we describe the molecular mechanisms to regulate heme biosynthesis not only in the liver but also in erythroid cells.
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