Table 1.

Rate-controlling enzymes of heme biosynthesis, catabolism and major mechanisms for their regulation.

Rate-Controlling Enzyme	Tissue Origin Subcellular Location	Gene and Chromosome Location	Gene Regulation
Heme Biosynthesis ALAS1 ALAS2	Ubiquitous Mitochondria Bone marrow Mitochondria	ALAS1 3p31.2 ALAS2 Xp11.2	Transcriptional regulation: Down-regulation by heme, glucose and sugars Induction by chemical, drugs, stress, circadian rhythm Post-transcriptional regulation: Destabilization of ALAS1 mRNA by heme Post-translational regulation: Impediment to pre-ALAS1 import into mitochondria Degradation of ALAS1 protein by heme Up-regulation by hypoxia and iron
Heme Catabolism HMOX1 HMOX2	Ubiquitous Mainly in smooth endoplasmic reticulum, mitochondria and nucleus Brain and testes Smooth endoplasmic reticulum	HMOX1 22q12.3	Transcriptional regulation: Up-regulation by heme and other metalloporphyrins Down-regulation by metalloporphyrins Induction by chemical and physical stresses Genetic polymorphisms Translational regulation: miRNAs Alternative splicing in the 5′-UTR