The role of heme in gene expression.

Recent evidence indicates that there are significant tissue-specific expression and heme-mediated regulation of enzymes in the heme biosynthetic pathway. In particular, delta-aminolevulinate synthase (ALAS) [EC 2.3.1.37] has been shown to exist as tissue-specific isozymes, i.e. the erythroid and non-specific ALAS, which are coded by two separate genes. In mammals, ALAS activity can be found in many tissues, the highest activity being found in the Harderian gland in rodents, the liver of chemically induced porphyric animals, and developing erythroblasts. In the liver, ALAS expression is under negative control by heme, while in the developing erythroblasts it is positively influenced by heme. In contrast to these tissues, ALAS is maximally expressed in the Harderian gland and is not influenced by heme. In addition to the tissue-specific regulation of heme biosynthesis, heme has also been shown to influence a number of gene functions that are not directly related to heme synthesis in various tissues.