Molecular mechanism of heme biosynthesis

The Tohoku Journal of Experimental Medicine
H Fujita

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.

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Citations

Sep 10, 2003·Biochemical Pharmacology·Kiichi NakahiraKiyoshi Morita
Jan 26, 2013·BMC Physiology·Aline C CaetanoRosangela M N Bezerra
May 28, 2016·Scientific Reports·Caihong WeiLixin Du
Oct 29, 2003·The Tohoku Journal of Experimental Medicine·Shigeki Shibahara
Dec 21, 2002·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Mei-Sze ChuaMinnie M Sarwal
Jun 3, 2021·International Journal of Molecular Sciences·Stefan W Ryter

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