Heme is a prosthetic group of hemoproteins playing important roles in
oxygen transport, detoxification, circadian rhythm,
microRNA processing, regulation of transcription, and translation. The majority of
heme (-85%) is synthesized in red blood cells mainly for
hemoglobin production, whereas hepatocytes account for most of the rest, functioning primarily in the synthesis of
cytochrome P450 enzymes and mitochondrial respiratory
enzymes. Thus, failure of
heme biosynthesis causes severe inherited or acquired disorders in humans, including
porphyria and
sideroblastic anemia. The
heme biosynthetic pathway is composed of eight
enzymes that work in either mitochondria or the cytoplasm, which have been extensively researched and frequently reviewed. On the other hand, the mechanisms governing transport and intracellular trafficking of
heme intermediates, as well as their potential links to human diseases, are poorly understood. Herein, we focus on recent understanding of the
heme biosynthetic pathway and on human disorders due to defective
heme synthesis in erythroid cells, such as
X-linked sideroblastic anemia and
erythropoietic protoporphyria.