title: Molecular mechanism of heme biosynthesis.
abstract: Two of the major organs producing heme are bone marrow and the liver. delta-Aminolevulinate synthase (ALAS) plays the key role to regulate heme biosynthesis in hepatocytes 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 a negative feedback manner. The way to regulate ALAS-N in the liver is suitable to supply a constant level of heme for a family of drug metabolizing enzymes, cytochrome P-450 (CYP). In erythroid tissues, not only erythroid-specific isozyme of ALAS (ALAS-E) but also ALAS-N are expressed, and regulated by distinctive manners. Although heme regulates ALAS-N in a negative feedback manner even in erythroid cells, ALAS-E is upregulated by induced heme concentration. ALAS-N in undifferentiated erythroid cells, therefore, is suggested to produce heme for CYP, whereas heme for accumulating hemoglobin (Hb) in cells undergoing differentiation is synthesized via ALAS-E. In this article, we describe the molecular mechanisms to regulate heme biosynthesis in non-erythroid as well as in erythroid tissues, and discuss the pathological significance of the mechanisms in patients with inherited disorders, porphyrias.
authors.affiliation: Department of Molecular Biology & Applied Physiology, Tohoku University School of Medicine, Sendai.
authors.forename: H
authors.initials: H
authors.lastname: Fujita
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000378:metabolism*; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D006418:Heme / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism*
chemical_list: D006418:Heme; D000624:5-Aminolevulinate Synthetase