Hypoxia decreases the expression of the two enzymes responsible for producing linear and cyclic tetrapyrroles in the heme biosynthetic pathway.

Heme is synthesized in all cell types in aerobic organisms. Hydroxymethylbilane synthase (HMBS) and uroporphyrinogen III synthase (UROS) catalyze two consecutive reactions in the heme biosynthetic pathway, generating the first linear and the first cyclic tetrapyrroles, respectively. Each of the HMBS and UROS genes contains the two separate promoters that generate ubiquitous and erythroid-specific mRNAs.

Heme as a magnificent molecule with multiple missions: heme determines its own fate and governs cellular homeostasis.

Heme is a prosthetic group of various types of proteins, such as hemoglobin, myoglobin, cytochrome c, cytochrome p450, catalase and peroxidase. In addition, heme is involved in a variety of biological events by modulating the function or the state of hemoproteins. For example, protein synthesis is inhibited in erythroid cells under heme deficiency, as the consequence of the activation of heme-regulated inhibitor (HRI).